Objective:To determine the anticancer potential of the methanolic extract from Ephedra alata against breast cancer both in vitro and in vivo.Methods:The effects of the methanolic extract of Ephedra alata on the viabil...Objective:To determine the anticancer potential of the methanolic extract from Ephedra alata against breast cancer both in vitro and in vivo.Methods:The effects of the methanolic extract of Ephedra alata on the viability,migration as well as apoptosis of breast cancer 4T1 cells were measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay,Transwell assay,and annexin V-FITC staining assay,respectively.Histological examination was also carried out.Moreover,a murine breast cancer model was established to evaluate the inhibitory effect of the extract.Biochemical parameters including hepatic and non-hepatic enzymes,malondialdehyde,and glutathione were investigated.Results:The methanolic extract of Ephedra alata showed a strong anti-proliferative and anti-migratory activity against 4T1 cells in a dose-dependent manner.It also induced apoptosis in 4T1 cells.In an in vivo mouse model,the extract markedly inhibited tumor growth,reduced malondialdehyde,and hepatic and non-hepatic enzymes as well as increased glutathione level.Conclusions:The methanolic extract of Ephedra alata inhibits breast cancer in vitro and in vivo,which may be a promising anticancer agent.展开更多
Objective:To investigate the potential synergistic activity of diclofenac with piperine and D-limonene in inducing apoptosis and cell cycle arrest in breast cancer MCF-7 cells.Methods:Molecular docking study was condu...Objective:To investigate the potential synergistic activity of diclofenac with piperine and D-limonene in inducing apoptosis and cell cycle arrest in breast cancer MCF-7 cells.Methods:Molecular docking study was conducted to evaluate the binding affinity of diclofenac with piperine and D-limonene against p53,Bax,and Bcl-2.The MTT assay was used to determine IC50,and the Chou-Talay method was used to determine the synergistic concentration of the combination treatment of diclofenac plus piperine and diclofenac plus D-limonene.Apoptosis detection,cell cycle arrest,reactive oxygen species production,and mitochondrial membrane potential were also investigated.Results:Diclofenac,piperine,and D-limonene showed potent binding affinity for p53,Bax,and Bcl-2.Diclofenac plus piperine and diclofenac plus D-limonene enhanced the formation of reactive oxygen species,which also had an effect on the mitochondrial membrane’s integrity and caused DNA fragmentation.Diclofenac plus piperine and diclofenac plus D-limonene arrested the cells in the sub-G0phase while drastically lowering the percentage of cells in the G2/M phase.Furthermore,the elevated apoptosis in the combined therapy was confirmed by annexin V/propidium iodide staining.Conclusions:The combined therapy prominently enhanced the antiproliferative and apoptotic effects on MCF-7 cells compared with treatment with diclofenac,piperine,and D-limonene alone.展开更多
Objective:To investigate the role of macrophages in regulating breast cancer cell migration and its related mechanisms.Methods:Human leukemia monocytic cell line THP-1-secreted exosomes were isolated using multi-step ...Objective:To investigate the role of macrophages in regulating breast cancer cell migration and its related mechanisms.Methods:Human leukemia monocytic cell line THP-1-secreted exosomes were isolated using multi-step ultracentrifugation and verified using nanoparticle tracking analysis.Differentially expressed miRNAs were identified using RNA sequencing.Overexpression of inhibitors of hsa-miR-101-3p in breast cancer MDA-MB-231 cells was performed by infecting their lentiviral constructs.The luciferase reporter assay was used to evaluate the interaction of DLG5 and miR-101.DGL5 expression was detected using qRT-PCR and Western blot analyses.Results:The migration of breast cancer cells was significantly inhibited after addition of exosomes.RNA sequencing results showed that miR-101-3p expression was significantly upregulated.Targetscan analysis predicted that miR-101-3p could target DLG5,and this prediction was verified using the luciferase assay.The addition of the miR-101-3p precursor significantly increased the expression of miR-101-3p,and the mRNA and protein levels of DLG5 were suppressed.In contrast,inhibiting the expression of miR-101-3p increased the mRNA and protein levels of DLG5.Furthermore,the scratch assay showed that inhibiting miR-101-3p could promote the migration of MDA-MB-231 cells.Conclusions:Macrophage exosomes can inhibit the migration of breast cancer cells,and increasing the expression of miR-101-3p to inhibit DLG5 expression may play an important role in this process,which needs further investigation.展开更多
Invasion and metastasis are important hallmarks of breast cancer and are the leading cause of patient mortality.Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer characterized by a poor progn...Invasion and metastasis are important hallmarks of breast cancer and are the leading cause of patient mortality.Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer characterized by a poor prognosis and a lackof effective targeted therapies. The present study investigated the inhibitory effect of a novel FTY720 derivative on theinvasive phenotype of TNBC cells. Here, we showed that a novel compound with an isoxazole ring, 4-(3-Decylisoxazol-5-yl)-1-hydroxy-2-(hydroxymethyl)butan-2-aminium chloride (CM2-II-173), significantly inhibitedinvasiveness of MDA-MB-231 TNBC cells. Expression of matrix metalloproteinase (MMP)-9 and invasiveness ofMCF10A normal breast cells induced by sphingosine-1-phosphate (S1P) were reduced by CM2-II-173 treatment.Activations of pMEK1, pAkt, pERK, and p38 MAPK by S1P were inhibited by treatment with CM2-II-173.Proliferation and anchorage-independent growth of MDA-MB-231 TNBC cells were significantly decreased by CM2-II-173. CM2-II-173 efficiently induced apoptosis in MDA-MB-231 TNBC cells. CM2-II-173 significantly inhibitedinvasive phenotypes of breast, liver, prostate, and ovarian cancer cells. CM2-II-173 exhibited a more potent effect onthe invasiveness of MDA-MB-231 TNBC cells compared to FTY720. Taken together, this study demonstrated thatCM2-II-173 has the potential to be a lead compound that can inhibit cancer progression of not only TNBC cells, butalso of liver, prostate, and ovarian cancer cells.展开更多
Backgorund:Fruits and seed extracts of Annona montana have significant cytotoxic potential in several cancer cells.This study evaluates the effect of A.montana leaves hexane extract on several signaling cascades and g...Backgorund:Fruits and seed extracts of Annona montana have significant cytotoxic potential in several cancer cells.This study evaluates the effect of A.montana leaves hexane extract on several signaling cascades and gene expression in metastatic breast cancer cells upon insulin-like growth factor-1(IGF-1)stimulation.Methods:MTT assay was performed to determine the proliferation of cancer cells.Propidium iodide staining and flow cytometry analysis of Annexin V binding was utilized to measure the progression of the cell cycle and the induction of apoptosis.Protein expression and phosphorylation were determined by western blotting analysis to examine the underlying cellular mechanism triggered upon treatment with A.montana leaves hexane extract.Results:A.montana leaves hexane(subfraction V)blocked the constitutive stimulation of the PI3K/mTOR signaling pathways.This inhibitory effect was associated with apoptosis induction as evidenced by the positivity with Annexin V and terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNNEL)staining,activation of caspase-3,and cleavage of PPAR.It also limited the expression of various downstream genes that regulate proliferation,survival,metastasis,and angiogenesis(i.e.,cyclin D1,survivin,COX-2,and VEGF).It increased the expression of p53 and p21.Interestingly,we also observed that this extract blocked the activation of AKT and ERK without affecting the phosphorylation of the IGF-1 receptor and activation of Ras upon IGF-1 stimulation.Conclusion:Our study indicates that A.montana leaves(sub-fraction V)extract exhibits a selective anti-proliferative and proapoptotic effect on the metastatic MDA-MB-231 breast cancer cells through the involvement of PI3K/AKT/mTOR/S6K1 pathways.展开更多
Breast cancer in women is a complicated and multifaceted disease. Studies have demonstrated that hyperglycemia is one of the most significant risk factors for breast cancer. Hyperglycemia is when the sugar level in hu...Breast cancer in women is a complicated and multifaceted disease. Studies have demonstrated that hyperglycemia is one of the most significant risk factors for breast cancer. Hyperglycemia is when the sugar level in human blood is too high, which means excess glucose. Glucose excess can encourage the growth, invasion, and migration of breast cancer cells at the cellular level. Though, the effects of glucose on the dynamics of breast cancer cells have been examined mathematically by a system of ordinary differential equations. However, the non-instantaneous biological occurrences leading to the secretion of immuno-suppressive cytokines by tumors to evade immune surveillance and the immune cells’ derivation of cytokines to attack the tumor cells are not yet discussed. Therefore, investigating the biological process involved in the dynamics of tumors, immune and normal cells with excessive glucose concentration is inviolable to determining the best procedure for controlling tumors’ uncontrollable growth. Time delay, denoted by τ, is used to describe the time tumor cells take to secrete immunosuppressive cytokines to evade immune surveillance and the time immune cells take to recognize and attack the tumor cells. We have studied the local stability analysis of the biological steady states in both delayed and non-delayed system. The Routh-Hurwitz stability criterion is used to analyze the dynamical equilibrium of the cells’ population. Hopf bifurcation was analyzed by using time delay s as a bifurcation parameter. The analytical results suggest an unstable scenario for a tumor-free equilibrium point as normal cells are bound to grow to their carrying capacity. The result predicts a stable system for coexisting equilibrium when the interaction is instantaneous (τ = 0). However, when τ > 0, the coexisting equilibrium point switches from stable to unstable. The numerical results not only validate all the analytical results but also show the case of possible situations when glucose concentration is varied, indicating that both tumor growth and immune system efficiency are highly affected by the level of glucose in the blood. This concluded that the delay in the secretion of cytokines by immune cells and derivation cytokines by the tumors helps to identify the possible chaotic situation under different glucose concentration and the extent to which such delay can have on restoration of the normal cells when glucose concentration is low.展开更多
Triple Negative Breast Cancer (TNBC) is a malignant form of cancer with very high mortality and morbidity. Epithelial to Mesenchymal Transition (EMT) is the most common pathophysiological change observed in cancer cel...Triple Negative Breast Cancer (TNBC) is a malignant form of cancer with very high mortality and morbidity. Epithelial to Mesenchymal Transition (EMT) is the most common pathophysiological change observed in cancer cells of epithelial origin that promotes metastasis, drug resistance and cancer stem cell formation. Since the information regarding differential gene expression in TNBC cells and cell signaling events leading to EMT is limited, this investigation was done by comparing transcriptomic data generated by RNA isolation and sequencing of a EMT model TNBC cell line in comparison to regular TNBC cells. RNA sequencing and Ingenuity Pathway Software Analysis (IPA) of the transcriptomic data revealed several upregulated and downregulated gene expressions along with novel core canonical pathways including Sirtuin signaling, Oxidative Phosphorylation and Mitochondrial dysfunction events involved in EMT changes of the TNBC cells.展开更多
Objective:To investigate the effect of piperine on human breast cancer cells.Methods:The effect of piperine on proliferation and migration of human breast cancer cells,MCF-7 and MDA-MB-231,was investigated using colon...Objective:To investigate the effect of piperine on human breast cancer cells.Methods:The effect of piperine on proliferation and migration of human breast cancer cells,MCF-7 and MDA-MB-231,was investigated using colony formation assays,wound healing assays,Matrigel migration assays,flow cytometry,RT-qPCR,and Western blotting assays.Results:Piperine inhibited the growth of MCF-7 and MDA-MB-231 cells and suppressed colony formation.Cell reduction at the G_(0)/G_(1) phase and cell arrest at the G_(2)/M phase were observed in breast cancer cells.However,the significant effect was only demonstrated in MDA-MB-231 cells.Moreover,cancer cell migration was suppressed by piperine at low concentration.RT-qPCR and Western blotting assays showed that piperine downregulated Rac1 gene and protein expression.Conclusions:Piperine could inhibit growth and migration of breast cancer cells by reducing Rac1 gene and protein expression.展开更多
The focus of this research is on the study of a series of copper (II) benzoylpyridine thiosemicarbazone complexes. Of the six benzoylpyridine thiosemicarbazone ligands used in this study, two are reported for the firs...The focus of this research is on the study of a series of copper (II) benzoylpyridine thiosemicarbazone complexes. Of the six benzoylpyridine thiosemicarbazone ligands used in this study, two are reported for the first time;2-benzoylpyridine tert-butyl thiosemicarbazone (BZP-tBTSC), and 2-benzoylpyridine benzyl thiosemicarbazone (BZP-BzTSC). Once characterized by NMR, melting point, and MS, these mono-anionic tridentate ligands were then reacted with Cu<sup>2+</sup> to form the new square planar metal complexes [Cu(BZP-tBTSC)Cl] and [Cu(BZP-BzTSC)Cl]. All of the copper complexes display marked inhibition of human topoisomerase IIα. The [Cu(BZP-tBTSC)Cl] complex shows marked activity against human breast cancer cell lines.展开更多
To investigate the correlation between the activity of kinases in the growth factor signal transduction pathway and the development of resistance of breast cancer to tamoxifen, reporter gene regulated by the regulatin...To investigate the correlation between the activity of kinases in the growth factor signal transduction pathway and the development of resistance of breast cancer to tamoxifen, reporter gene regulated by the regulating fragment of CCD1 was transfected into the MCF 7 cells, and the influence of tamoxifen on the reporter gene expression was examined under different conditions of TPA treatment. Our results showed that the reporter gene expression was inhibited by tamoxifen and promoted by TPA. Furthermore, tamoxifen exerts an agonist effect on the reporter gene expression when the cells was treated by TPA previously for 12 h. It is concluded that TPA could induce estrogen like effect of tamoxifen on estrogen receptor positive breast cancer cells and it may be one of the mechanisms responsible for the development of tamoxifen resistance.展开更多
Angiotensin-(1-7) [Ang-(1-7)] is a heptapeptide of the renin-angiotensin system with vasodilator and anti-proliferative properties. In the present study, we aim to investigate whether Ang-(1-7) induces apoptosis in br...Angiotensin-(1-7) [Ang-(1-7)] is a heptapeptide of the renin-angiotensin system with vasodilator and anti-proliferative properties. In the present study, we aim to investigate whether Ang-(1-7) induces apoptosis in breast cancer cells and whether the altered expression of apoptosis-related genes is involved in this process. Human breast cell line T47D was treated with angiotensin-(1-7) and angiotensin II (Ang II). Cell proliferation and apoptosis were quantified using hemocytometer and flow cytometry, respectively. The expression of 84 apoptosis-related genes was evaluated through qPCR array. Ang-(1-7), as opposed to Ang II, decreased proliferation and increased apoptosis in T47D cells. Moreover, many pro-apoptotic genes were up-regulated, such as BAK1, BAX, BCL2L1, BID and BIK. In addition, some anti-apoptotic genes as AKT1 and XIAP were down-regulated by heptapeptide. Although a deeper study should be performed, our results support the hypothesis that Ang-(1-7) could change the expression of several genes related to apoptosis, interfering directly in the molecular pathways associated with the survival of breast cancer cells.展开更多
To investigate exogenous PTEN gene transfected human breast cancer cell line MDA-MD-468.Methods Using the lipofectamine 2000 transfection technique,wild type PTEN gene was transducted into an in vitro cultured highly ...To investigate exogenous PTEN gene transfected human breast cancer cell line MDA-MD-468.Methods Using the lipofectamine 2000 transfection technique,wild type PTEN gene was transducted into an in vitro cultured highly metastatic breast cancer cell line MDA-MD-468.After transfection,the cells were selected by G418.The resistant clones were chosen and expanded in DMEM culture medium.RT-PCR,immunohistochemical method and western blot were used to determine the expression of target genes.Results An anti-G418 cell clone was established and expanded in culture.The transfected PTEN gene MDA-MD-468 cells showed expression of PTEN mRNA and PTEN protein.Conclusion Human breast cancer cell line MDA-MB-468 established in this study expresses consistently exogenous PTEN genes.4 refs,6 figs.展开更多
Recent studies have revealed that osthole,an active constituent isolated from the fruit of Cnidium monnieri(L.) Cusson,a traditional Chinese medicine,possesses anticancer activity.However,its effect on breast cancer c...Recent studies have revealed that osthole,an active constituent isolated from the fruit of Cnidium monnieri(L.) Cusson,a traditional Chinese medicine,possesses anticancer activity.However,its effect on breast cancer cells so far has not been elucidated clearly.In the present study,we evaluated the effects of osthole on the proliferation,cell cycle and apoptosis of human breast cancer cells MDA-MB 435.We demonstrated that osthole is effective in inhibiting the proliferation of MDA-MB 435 cells,The mitochondrion-mediated apoptotic pathway was involved in apoptosis induced by osthole,as indicated by activation of caspase-9 and caspase-3 followed by PARP degradation.The mechanism underlying its effect on the induction of G1 phase arrest was due to the up-regulation of p53 and p21 and down-regulation of Cdk2 and cyclin D1 expression.Were observed taken together,these findings suggest that the anticancer efficacy of osthole is mediated via induction of cell cycle arrest and apoptosis in human breast cancer cells and osthole may be a potential chemotherapeutic agent against human breast cancer.展开更多
Objective: To study the regulatory effects of miR-21 on breast cancer cell line proliferation and invasion as well as the downstream target genes. Methods: Breast cancer cell lines MCF-7 were cultured and transfected ...Objective: To study the regulatory effects of miR-21 on breast cancer cell line proliferation and invasion as well as the downstream target genes. Methods: Breast cancer cell lines MCF-7 were cultured and transfected with miR-21 mimics and the corresponding negative control mimics(NC mimics), and then MTS kits were used to detect cell viability. Transwell experiment was used to detect cell invasion ability, and fluorescence quantitative PCR was used to detect the expression of proliferation and invasion-related genes in cells. Results: 24 h after transfection of miR-21 mimics and NC mimics, cell OD value and the number of invasive cells of miR-21 group were significantly higher than those of NC group, and m RNA contents of PDCD-4, Fas L, PTEN, Rho B, Maspin, TIMP3 and RECK in cells were significantly lower than those of NC group. Conclusion: miR-21 can promote the proliferation and invasion of breast cancer cell lines, and its downstream target genes include PDCD-4, Fas L, PTEN, Rho B, Maspin, TIMP3 and RECK.展开更多
Objective:To study whether the infection of Schistosomiasis japanicum(S.japanicum) is related to enhanced proliferation and migration of cancer cells,and the molecular mechanism pertains to cancer cell metastasis in h...Objective:To study whether the infection of Schistosomiasis japanicum(S.japanicum) is related to enhanced proliferation and migration of cancer cells,and the molecular mechanism pertains to cancer cell metastasis in human host.Methods:The gene of S.japanicum glutathione transferase(sjGST) cloned from 5.japanicum was expressed,purified and applied in a series of assays to explore the effect of sjGST on proliferation and migration of MDA-MB-435S,and the expression of MMP2 and MMP9.Immunofluorescence assay for the binding of sjGST to MDA-MB-435S was also carried out.Results:Results showed that sjGST enhanced proliferation and migration in human breast cancer cell MDA-MB-435S signifycantly at 50-200 nM,but did not enhance them in human lung cancer cell A549.Immunofluorescence assay for the binding of sjGST to MDA-MB-435S and A549 showed that GST was readily hound to the breast cancer cells,but showed almost no binding to human lung cancer cells.The assays for gelatinase activity showed that both MMP2 and MMP9 activities were increased significantly in the presence of sjGST(50-200 nM) in MDA-MB-435S, but they were not significant in A549.Conclusions:Our current results show strongly that S. japanicum GST binds to MDA-MB-435S probably via its i'eceptor,and enhances proliferation and migration of the cancer cells by up-regulatory expression of MMP2 and MMP9.展开更多
Objective:To investigate the expression of targeting protein for Xenopus kinesin-like protein 2(TPX2) in breast cancer tissue and to explore its role in proliferation,migration and invasion of breast cancer cells.Meth...Objective:To investigate the expression of targeting protein for Xenopus kinesin-like protein 2(TPX2) in breast cancer tissue and to explore its role in proliferation,migration and invasion of breast cancer cells.Methods:The mRNA and protein expressions of TPX2 in breast cancer tissue and cell lines were assessed by quantitative RT-PCR and Western blot.The effect of TPX2 with RNA interference on proliferation,invasion and migration of breast cancer cells was observed by MTT and Transwell assays.Results:Both mRNA and protein expressions of TPX2 were upregulated in breast cancer tissues compared to tumor-adjacent tissue.TPX2 expression was also upregulated in breast cancer cell lines,and the TPX2 interfered by small interfering RNA could inhibit the proliferation,invasion and migration of breast cancer cells by inhibiting matrix metalloproteinase-2 and matrix metalloproteinase-9.Conclusions:Significantly upregulated TPX2 expression is observed in breast cancer tissue and cells,and contributes to promote the proliferation,migration and invasion of breast cancer cells.展开更多
The purpose of this study was to verify that a combination of mild hyperthermia and docetaxel chemotherapy produces synergistic antitumor effects and to explore the action mechanisms of this treatment approach.The eff...The purpose of this study was to verify that a combination of mild hyperthermia and docetaxel chemotherapy produces synergistic antitumor effects and to explore the action mechanisms of this treatment approach.The effects of docetaxel on the proliferation of cells from the estrogen receptor(ER)-positive human breast cancer cell line MCF-7 and the ER-negative human breast cancer cell line MDA-MB-453 were examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay,and effective experimental concentrations of docetaxel were determined.The effects of mild hyperthermia plus docetaxel therapy on apoptosis rate in the MCF-7 and MDA-MB-453 human breast cancer cell lines were analyzed by using flow cytometry with Annexin-V fluorescein isothiocyanate(FITC)/propidium iodide(PI)staining.The effects of these combined treatments on cell cycle progression in the MCF-7 and MDA-MB-453 human breast cancer cell lines were examined by using flow cytometry.The effects of these combined treatments on the expression of apoptosis-related proteins and proteins in the mitogen-activated protein kinase(MAPK)pathways were analyzed by using Western blotting.The effects of these combined treatments on the expression of the heat shock protein 70(HSP70)and the multi-drug resistance(MDR)gene product P-glycoprotein(Pgp)were examined by using Western blotting.The results showed that the half-maximal inhibitory concentration(IC50)of docetaxel for MCF-7 and MDA-MB-453 cells was 19.57±1.12 and 21.64±2.31μmol/L respectively.Mild hyperthermia with docetaxel therapy could increase apoptosis rate in the MCF-7 and MDA-MB-453cells.Apoptosis rate in MCF-7 and MDA-MB-453 cells was increased from(23.66±3.59)%and(18.51±3.17)%in docetaxel treatment group to(47.12±6.73)%and(55.16±7.42)%in mild hyperthermia plus docetaxel group,indicating that the mild hyperthermia and docetaxel therapeutic approaches exhibited significant synergistic antitumor effects.Treatments of mild hyperthermia plus docetaxel induced G2/M cell cycle arrest in the MCF-7 and MDA-MB-453 cells.Western blotting demonstrated that proteins in the MAPK pathway were expressed at higher levels in docetaxel-treated cells following mild hypothermia than those in cells treated with docetaxel alone.As compared with blank control group,cells from the mild hyperthermia plus docetaxel group exhibited significantly decreased B-cell lymphoma 2(Bcl-2)protein expression but slightly increased Bcl-2-associated X protein(Bax)expression.Western blotting results revealed that HSP70 and Pgp expression levels were significantly increased following mild hypothermia.It was concluded that treatments of mild hyperthermia plus docetaxel inhibited the proliferation of human breast cancer cells,promoted apoptosis of breast cancer cells,and produced synergistic antitumor effects.展开更多
This study aimed to evaluate the effects of Pin1 inhibitor Juglone on proliferation, migration and the angiogenic ability of breast cancer cell line MCF7 Adr. MCF7 Adr cells were cultured and separately treated with P...This study aimed to evaluate the effects of Pin1 inhibitor Juglone on proliferation, migration and the angiogenic ability of breast cancer cell line MCF7 Adr. MCF7 Adr cells were cultured and separately treated with Pin1 inhibitor Juglone(treatment group) and DMEM without drug(control group). The cell cycle was examined by flow cytometry. Cell migration was measured by wound-healing assay. Cyclin E protein content was detected by Western blotting. The angiogenesis factor vascular endothelial growth factor(VEGF) in cell media was determined by enzyme linked immunosorbent assay. The results showed that the percentage of cells in G2/M phase in treatment group was significantly higher than that in control group(25.5% vs. 10.1%, P<0.05), and that in G0/G1 phase and S stage in treatment group was significantly lower than that in control group(40.5% vs. 48.2%, and 33.7% vs. 41.7%, P<0.05). Cyclin E protein content in treatment group was significantly lower than that in control group(39.2±7.4 vs. 100±23.1, P<0.05).(A0–A24)/A0 value in treatment group was significantly lower than that in control group(23.9±3.8 vs. 100±14.4, P<0.05). VEGF-A,-B, and-C contents in cell media of treatment group were significantly lower than those in control group(P<0.05). It was suggested that Pin1 inhibitor Juglone can effectively inhibit the proliferation, migration and the angiogenic ability of MCF7 Adr cells, and can be used as an alternative drug therapy for breast cancer.展开更多
Bisphenol-A(BPA) has been considered as an endocrine disrupting chemical(EDC) because it can exert estrogenic properties.For bisphenol-S(BPS) and bisphenol-F(BPF) that are BPA analogs and substitutes,their risk to est...Bisphenol-A(BPA) has been considered as an endocrine disrupting chemical(EDC) because it can exert estrogenic properties.For bisphenol-S(BPS) and bisphenol-F(BPF) that are BPA analogs and substitutes,their risk to estrogendependent cancer has been reported rarely compared with the numerous cases of BPA.In this study,we examined whether BPA,BPS,and BPF can lead to the proliferation,migration,and epithelial mesenchymal transition(EMT) of MCF-7 clonal variant(MCF-7 CV) breast cancer cells expressing estrogen receptors(ERs).In a cell viability assay,BPA,BPS,and BPF significantly increased proliferation of MCF-7 CV cells compared to control(DMSO) as did17β-estradiol(E2).In Western blotting assay,BPA,BPS,and BPF enhanced the protein expression of cell cycle progression genes such as cyclin D1 and E1.In addition,MCF-7 CV cells lost cell to cell contacts and acquired fibroblast-like morphology by the treatment of BPA,BPS,or BPF for 24 hours.In cell migration assay,BPA,BPS,and BPF accelerated the migration capability of MCF-7 CV cells as did E2.In relation with the EMT process,BPA,BPS,and BPF increased the protein expression of N-cadherin,while they decreased the protein expression of Ecadherin.When BPA,BPS,and BPF were co-treated with ICI 182,780,an ER antagonist,proliferation effects were reversed,the expression of cyclin D1 and cyclin E1 was downregulated,and the altered cell migration and expression of N-cadherin and E-cadherin by BPA,BPS,and BPF were restored to the control level.Thus,these results imply that BPS and BPF also have the risk of breast cancer progression as much as BPA in the induction of proliferation and migration of MCF-7 CV cells by regulating the protein expression of cell cycle-related genes and EMT markers via the ER-dependent pathway.展开更多
文摘Objective:To determine the anticancer potential of the methanolic extract from Ephedra alata against breast cancer both in vitro and in vivo.Methods:The effects of the methanolic extract of Ephedra alata on the viability,migration as well as apoptosis of breast cancer 4T1 cells were measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay,Transwell assay,and annexin V-FITC staining assay,respectively.Histological examination was also carried out.Moreover,a murine breast cancer model was established to evaluate the inhibitory effect of the extract.Biochemical parameters including hepatic and non-hepatic enzymes,malondialdehyde,and glutathione were investigated.Results:The methanolic extract of Ephedra alata showed a strong anti-proliferative and anti-migratory activity against 4T1 cells in a dose-dependent manner.It also induced apoptosis in 4T1 cells.In an in vivo mouse model,the extract markedly inhibited tumor growth,reduced malondialdehyde,and hepatic and non-hepatic enzymes as well as increased glutathione level.Conclusions:The methanolic extract of Ephedra alata inhibits breast cancer in vitro and in vivo,which may be a promising anticancer agent.
文摘Objective:To investigate the potential synergistic activity of diclofenac with piperine and D-limonene in inducing apoptosis and cell cycle arrest in breast cancer MCF-7 cells.Methods:Molecular docking study was conducted to evaluate the binding affinity of diclofenac with piperine and D-limonene against p53,Bax,and Bcl-2.The MTT assay was used to determine IC50,and the Chou-Talay method was used to determine the synergistic concentration of the combination treatment of diclofenac plus piperine and diclofenac plus D-limonene.Apoptosis detection,cell cycle arrest,reactive oxygen species production,and mitochondrial membrane potential were also investigated.Results:Diclofenac,piperine,and D-limonene showed potent binding affinity for p53,Bax,and Bcl-2.Diclofenac plus piperine and diclofenac plus D-limonene enhanced the formation of reactive oxygen species,which also had an effect on the mitochondrial membrane’s integrity and caused DNA fragmentation.Diclofenac plus piperine and diclofenac plus D-limonene arrested the cells in the sub-G0phase while drastically lowering the percentage of cells in the G2/M phase.Furthermore,the elevated apoptosis in the combined therapy was confirmed by annexin V/propidium iodide staining.Conclusions:The combined therapy prominently enhanced the antiproliferative and apoptotic effects on MCF-7 cells compared with treatment with diclofenac,piperine,and D-limonene alone.
基金supported by the Key Research and Development Program of Hainan Province(ZDYF2020139,ZDYF2018158)the Science and Technology Funding Project of Hainan Province(821MS129).
文摘Objective:To investigate the role of macrophages in regulating breast cancer cell migration and its related mechanisms.Methods:Human leukemia monocytic cell line THP-1-secreted exosomes were isolated using multi-step ultracentrifugation and verified using nanoparticle tracking analysis.Differentially expressed miRNAs were identified using RNA sequencing.Overexpression of inhibitors of hsa-miR-101-3p in breast cancer MDA-MB-231 cells was performed by infecting their lentiviral constructs.The luciferase reporter assay was used to evaluate the interaction of DLG5 and miR-101.DGL5 expression was detected using qRT-PCR and Western blot analyses.Results:The migration of breast cancer cells was significantly inhibited after addition of exosomes.RNA sequencing results showed that miR-101-3p expression was significantly upregulated.Targetscan analysis predicted that miR-101-3p could target DLG5,and this prediction was verified using the luciferase assay.The addition of the miR-101-3p precursor significantly increased the expression of miR-101-3p,and the mRNA and protein levels of DLG5 were suppressed.In contrast,inhibiting the expression of miR-101-3p increased the mRNA and protein levels of DLG5.Furthermore,the scratch assay showed that inhibiting miR-101-3p could promote the migration of MDA-MB-231 cells.Conclusions:Macrophage exosomes can inhibit the migration of breast cancer cells,and increasing the expression of miR-101-3p to inhibit DLG5 expression may play an important role in this process,which needs further investigation.
基金supported by the National Research Foundation of Korea(Nos.2016R1A6A1A03007648,2019R1A2C1009773,2018R1A5A2024425,and 2022R1A2C1093335).
文摘Invasion and metastasis are important hallmarks of breast cancer and are the leading cause of patient mortality.Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer characterized by a poor prognosis and a lackof effective targeted therapies. The present study investigated the inhibitory effect of a novel FTY720 derivative on theinvasive phenotype of TNBC cells. Here, we showed that a novel compound with an isoxazole ring, 4-(3-Decylisoxazol-5-yl)-1-hydroxy-2-(hydroxymethyl)butan-2-aminium chloride (CM2-II-173), significantly inhibitedinvasiveness of MDA-MB-231 TNBC cells. Expression of matrix metalloproteinase (MMP)-9 and invasiveness ofMCF10A normal breast cells induced by sphingosine-1-phosphate (S1P) were reduced by CM2-II-173 treatment.Activations of pMEK1, pAkt, pERK, and p38 MAPK by S1P were inhibited by treatment with CM2-II-173.Proliferation and anchorage-independent growth of MDA-MB-231 TNBC cells were significantly decreased by CM2-II-173. CM2-II-173 efficiently induced apoptosis in MDA-MB-231 TNBC cells. CM2-II-173 significantly inhibitedinvasive phenotypes of breast, liver, prostate, and ovarian cancer cells. CM2-II-173 exhibited a more potent effect onthe invasiveness of MDA-MB-231 TNBC cells compared to FTY720. Taken together, this study demonstrated thatCM2-II-173 has the potential to be a lead compound that can inhibit cancer progression of not only TNBC cells, butalso of liver, prostate, and ovarian cancer cells.
基金supported by the National Institutes of Health Grant SC1DK084343(to MAB)by Mass Spectrometry Research and Education Center must cite funding from NIH S10 OD021758-01A1.
文摘Backgorund:Fruits and seed extracts of Annona montana have significant cytotoxic potential in several cancer cells.This study evaluates the effect of A.montana leaves hexane extract on several signaling cascades and gene expression in metastatic breast cancer cells upon insulin-like growth factor-1(IGF-1)stimulation.Methods:MTT assay was performed to determine the proliferation of cancer cells.Propidium iodide staining and flow cytometry analysis of Annexin V binding was utilized to measure the progression of the cell cycle and the induction of apoptosis.Protein expression and phosphorylation were determined by western blotting analysis to examine the underlying cellular mechanism triggered upon treatment with A.montana leaves hexane extract.Results:A.montana leaves hexane(subfraction V)blocked the constitutive stimulation of the PI3K/mTOR signaling pathways.This inhibitory effect was associated with apoptosis induction as evidenced by the positivity with Annexin V and terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNNEL)staining,activation of caspase-3,and cleavage of PPAR.It also limited the expression of various downstream genes that regulate proliferation,survival,metastasis,and angiogenesis(i.e.,cyclin D1,survivin,COX-2,and VEGF).It increased the expression of p53 and p21.Interestingly,we also observed that this extract blocked the activation of AKT and ERK without affecting the phosphorylation of the IGF-1 receptor and activation of Ras upon IGF-1 stimulation.Conclusion:Our study indicates that A.montana leaves(sub-fraction V)extract exhibits a selective anti-proliferative and proapoptotic effect on the metastatic MDA-MB-231 breast cancer cells through the involvement of PI3K/AKT/mTOR/S6K1 pathways.
文摘Breast cancer in women is a complicated and multifaceted disease. Studies have demonstrated that hyperglycemia is one of the most significant risk factors for breast cancer. Hyperglycemia is when the sugar level in human blood is too high, which means excess glucose. Glucose excess can encourage the growth, invasion, and migration of breast cancer cells at the cellular level. Though, the effects of glucose on the dynamics of breast cancer cells have been examined mathematically by a system of ordinary differential equations. However, the non-instantaneous biological occurrences leading to the secretion of immuno-suppressive cytokines by tumors to evade immune surveillance and the immune cells’ derivation of cytokines to attack the tumor cells are not yet discussed. Therefore, investigating the biological process involved in the dynamics of tumors, immune and normal cells with excessive glucose concentration is inviolable to determining the best procedure for controlling tumors’ uncontrollable growth. Time delay, denoted by τ, is used to describe the time tumor cells take to secrete immunosuppressive cytokines to evade immune surveillance and the time immune cells take to recognize and attack the tumor cells. We have studied the local stability analysis of the biological steady states in both delayed and non-delayed system. The Routh-Hurwitz stability criterion is used to analyze the dynamical equilibrium of the cells’ population. Hopf bifurcation was analyzed by using time delay s as a bifurcation parameter. The analytical results suggest an unstable scenario for a tumor-free equilibrium point as normal cells are bound to grow to their carrying capacity. The result predicts a stable system for coexisting equilibrium when the interaction is instantaneous (τ = 0). However, when τ > 0, the coexisting equilibrium point switches from stable to unstable. The numerical results not only validate all the analytical results but also show the case of possible situations when glucose concentration is varied, indicating that both tumor growth and immune system efficiency are highly affected by the level of glucose in the blood. This concluded that the delay in the secretion of cytokines by immune cells and derivation cytokines by the tumors helps to identify the possible chaotic situation under different glucose concentration and the extent to which such delay can have on restoration of the normal cells when glucose concentration is low.
文摘Triple Negative Breast Cancer (TNBC) is a malignant form of cancer with very high mortality and morbidity. Epithelial to Mesenchymal Transition (EMT) is the most common pathophysiological change observed in cancer cells of epithelial origin that promotes metastasis, drug resistance and cancer stem cell formation. Since the information regarding differential gene expression in TNBC cells and cell signaling events leading to EMT is limited, this investigation was done by comparing transcriptomic data generated by RNA isolation and sequencing of a EMT model TNBC cell line in comparison to regular TNBC cells. RNA sequencing and Ingenuity Pathway Software Analysis (IPA) of the transcriptomic data revealed several upregulated and downregulated gene expressions along with novel core canonical pathways including Sirtuin signaling, Oxidative Phosphorylation and Mitochondrial dysfunction events involved in EMT changes of the TNBC cells.
基金financially supported by Mahasarakham University 2021(MSU2021).
文摘Objective:To investigate the effect of piperine on human breast cancer cells.Methods:The effect of piperine on proliferation and migration of human breast cancer cells,MCF-7 and MDA-MB-231,was investigated using colony formation assays,wound healing assays,Matrigel migration assays,flow cytometry,RT-qPCR,and Western blotting assays.Results:Piperine inhibited the growth of MCF-7 and MDA-MB-231 cells and suppressed colony formation.Cell reduction at the G_(0)/G_(1) phase and cell arrest at the G_(2)/M phase were observed in breast cancer cells.However,the significant effect was only demonstrated in MDA-MB-231 cells.Moreover,cancer cell migration was suppressed by piperine at low concentration.RT-qPCR and Western blotting assays showed that piperine downregulated Rac1 gene and protein expression.Conclusions:Piperine could inhibit growth and migration of breast cancer cells by reducing Rac1 gene and protein expression.
文摘The focus of this research is on the study of a series of copper (II) benzoylpyridine thiosemicarbazone complexes. Of the six benzoylpyridine thiosemicarbazone ligands used in this study, two are reported for the first time;2-benzoylpyridine tert-butyl thiosemicarbazone (BZP-tBTSC), and 2-benzoylpyridine benzyl thiosemicarbazone (BZP-BzTSC). Once characterized by NMR, melting point, and MS, these mono-anionic tridentate ligands were then reacted with Cu<sup>2+</sup> to form the new square planar metal complexes [Cu(BZP-tBTSC)Cl] and [Cu(BZP-BzTSC)Cl]. All of the copper complexes display marked inhibition of human topoisomerase IIα. The [Cu(BZP-tBTSC)Cl] complex shows marked activity against human breast cancer cell lines.
基金This project was supported by a grant of the National Nat-ural Sciences Foundation of China (No.39770 72 4)
文摘To investigate the correlation between the activity of kinases in the growth factor signal transduction pathway and the development of resistance of breast cancer to tamoxifen, reporter gene regulated by the regulating fragment of CCD1 was transfected into the MCF 7 cells, and the influence of tamoxifen on the reporter gene expression was examined under different conditions of TPA treatment. Our results showed that the reporter gene expression was inhibited by tamoxifen and promoted by TPA. Furthermore, tamoxifen exerts an agonist effect on the reporter gene expression when the cells was treated by TPA previously for 12 h. It is concluded that TPA could induce estrogen like effect of tamoxifen on estrogen receptor positive breast cancer cells and it may be one of the mechanisms responsible for the development of tamoxifen resistance.
基金supported by grants number 2008/54383-0,2010/03658-9 and 2011/08531-0 from the Sao Paulo Research Foundation(FAPESP)-Brazil.
文摘Angiotensin-(1-7) [Ang-(1-7)] is a heptapeptide of the renin-angiotensin system with vasodilator and anti-proliferative properties. In the present study, we aim to investigate whether Ang-(1-7) induces apoptosis in breast cancer cells and whether the altered expression of apoptosis-related genes is involved in this process. Human breast cell line T47D was treated with angiotensin-(1-7) and angiotensin II (Ang II). Cell proliferation and apoptosis were quantified using hemocytometer and flow cytometry, respectively. The expression of 84 apoptosis-related genes was evaluated through qPCR array. Ang-(1-7), as opposed to Ang II, decreased proliferation and increased apoptosis in T47D cells. Moreover, many pro-apoptotic genes were up-regulated, such as BAK1, BAX, BCL2L1, BID and BIK. In addition, some anti-apoptotic genes as AKT1 and XIAP were down-regulated by heptapeptide. Although a deeper study should be performed, our results support the hypothesis that Ang-(1-7) could change the expression of several genes related to apoptosis, interfering directly in the molecular pathways associated with the survival of breast cancer cells.
文摘To investigate exogenous PTEN gene transfected human breast cancer cell line MDA-MD-468.Methods Using the lipofectamine 2000 transfection technique,wild type PTEN gene was transducted into an in vitro cultured highly metastatic breast cancer cell line MDA-MD-468.After transfection,the cells were selected by G418.The resistant clones were chosen and expanded in DMEM culture medium.RT-PCR,immunohistochemical method and western blot were used to determine the expression of target genes.Results An anti-G418 cell clone was established and expanded in culture.The transfected PTEN gene MDA-MD-468 cells showed expression of PTEN mRNA and PTEN protein.Conclusion Human breast cancer cell line MDA-MB-468 established in this study expresses consistently exogenous PTEN genes.4 refs,6 figs.
基金supported by grant from the Natural Science Foundation of Jiangsu Province(No.BK2011140)
文摘Recent studies have revealed that osthole,an active constituent isolated from the fruit of Cnidium monnieri(L.) Cusson,a traditional Chinese medicine,possesses anticancer activity.However,its effect on breast cancer cells so far has not been elucidated clearly.In the present study,we evaluated the effects of osthole on the proliferation,cell cycle and apoptosis of human breast cancer cells MDA-MB 435.We demonstrated that osthole is effective in inhibiting the proliferation of MDA-MB 435 cells,The mitochondrion-mediated apoptotic pathway was involved in apoptosis induced by osthole,as indicated by activation of caspase-9 and caspase-3 followed by PARP degradation.The mechanism underlying its effect on the induction of G1 phase arrest was due to the up-regulation of p53 and p21 and down-regulation of Cdk2 and cyclin D1 expression.Were observed taken together,these findings suggest that the anticancer efficacy of osthole is mediated via induction of cell cycle arrest and apoptosis in human breast cancer cells and osthole may be a potential chemotherapeutic agent against human breast cancer.
基金supported by National Natural Science Foundation of China(Grant No.:81560269)
文摘Objective: To study the regulatory effects of miR-21 on breast cancer cell line proliferation and invasion as well as the downstream target genes. Methods: Breast cancer cell lines MCF-7 were cultured and transfected with miR-21 mimics and the corresponding negative control mimics(NC mimics), and then MTS kits were used to detect cell viability. Transwell experiment was used to detect cell invasion ability, and fluorescence quantitative PCR was used to detect the expression of proliferation and invasion-related genes in cells. Results: 24 h after transfection of miR-21 mimics and NC mimics, cell OD value and the number of invasive cells of miR-21 group were significantly higher than those of NC group, and m RNA contents of PDCD-4, Fas L, PTEN, Rho B, Maspin, TIMP3 and RECK in cells were significantly lower than those of NC group. Conclusion: miR-21 can promote the proliferation and invasion of breast cancer cell lines, and its downstream target genes include PDCD-4, Fas L, PTEN, Rho B, Maspin, TIMP3 and RECK.
基金Supported by grants from National Science Council(NSC98-2314-B-110-001-MY3)
文摘Objective:To study whether the infection of Schistosomiasis japanicum(S.japanicum) is related to enhanced proliferation and migration of cancer cells,and the molecular mechanism pertains to cancer cell metastasis in human host.Methods:The gene of S.japanicum glutathione transferase(sjGST) cloned from 5.japanicum was expressed,purified and applied in a series of assays to explore the effect of sjGST on proliferation and migration of MDA-MB-435S,and the expression of MMP2 and MMP9.Immunofluorescence assay for the binding of sjGST to MDA-MB-435S was also carried out.Results:Results showed that sjGST enhanced proliferation and migration in human breast cancer cell MDA-MB-435S signifycantly at 50-200 nM,but did not enhance them in human lung cancer cell A549.Immunofluorescence assay for the binding of sjGST to MDA-MB-435S and A549 showed that GST was readily hound to the breast cancer cells,but showed almost no binding to human lung cancer cells.The assays for gelatinase activity showed that both MMP2 and MMP9 activities were increased significantly in the presence of sjGST(50-200 nM) in MDA-MB-435S, but they were not significant in A549.Conclusions:Our current results show strongly that S. japanicum GST binds to MDA-MB-435S probably via its i'eceptor,and enhances proliferation and migration of the cancer cells by up-regulatory expression of MMP2 and MMP9.
基金Supported by National Science Foundation(81502322)
文摘Objective:To investigate the expression of targeting protein for Xenopus kinesin-like protein 2(TPX2) in breast cancer tissue and to explore its role in proliferation,migration and invasion of breast cancer cells.Methods:The mRNA and protein expressions of TPX2 in breast cancer tissue and cell lines were assessed by quantitative RT-PCR and Western blot.The effect of TPX2 with RNA interference on proliferation,invasion and migration of breast cancer cells was observed by MTT and Transwell assays.Results:Both mRNA and protein expressions of TPX2 were upregulated in breast cancer tissues compared to tumor-adjacent tissue.TPX2 expression was also upregulated in breast cancer cell lines,and the TPX2 interfered by small interfering RNA could inhibit the proliferation,invasion and migration of breast cancer cells by inhibiting matrix metalloproteinase-2 and matrix metalloproteinase-9.Conclusions:Significantly upregulated TPX2 expression is observed in breast cancer tissue and cells,and contributes to promote the proliferation,migration and invasion of breast cancer cells.
文摘The purpose of this study was to verify that a combination of mild hyperthermia and docetaxel chemotherapy produces synergistic antitumor effects and to explore the action mechanisms of this treatment approach.The effects of docetaxel on the proliferation of cells from the estrogen receptor(ER)-positive human breast cancer cell line MCF-7 and the ER-negative human breast cancer cell line MDA-MB-453 were examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay,and effective experimental concentrations of docetaxel were determined.The effects of mild hyperthermia plus docetaxel therapy on apoptosis rate in the MCF-7 and MDA-MB-453 human breast cancer cell lines were analyzed by using flow cytometry with Annexin-V fluorescein isothiocyanate(FITC)/propidium iodide(PI)staining.The effects of these combined treatments on cell cycle progression in the MCF-7 and MDA-MB-453 human breast cancer cell lines were examined by using flow cytometry.The effects of these combined treatments on the expression of apoptosis-related proteins and proteins in the mitogen-activated protein kinase(MAPK)pathways were analyzed by using Western blotting.The effects of these combined treatments on the expression of the heat shock protein 70(HSP70)and the multi-drug resistance(MDR)gene product P-glycoprotein(Pgp)were examined by using Western blotting.The results showed that the half-maximal inhibitory concentration(IC50)of docetaxel for MCF-7 and MDA-MB-453 cells was 19.57±1.12 and 21.64±2.31μmol/L respectively.Mild hyperthermia with docetaxel therapy could increase apoptosis rate in the MCF-7 and MDA-MB-453cells.Apoptosis rate in MCF-7 and MDA-MB-453 cells was increased from(23.66±3.59)%and(18.51±3.17)%in docetaxel treatment group to(47.12±6.73)%and(55.16±7.42)%in mild hyperthermia plus docetaxel group,indicating that the mild hyperthermia and docetaxel therapeutic approaches exhibited significant synergistic antitumor effects.Treatments of mild hyperthermia plus docetaxel induced G2/M cell cycle arrest in the MCF-7 and MDA-MB-453 cells.Western blotting demonstrated that proteins in the MAPK pathway were expressed at higher levels in docetaxel-treated cells following mild hypothermia than those in cells treated with docetaxel alone.As compared with blank control group,cells from the mild hyperthermia plus docetaxel group exhibited significantly decreased B-cell lymphoma 2(Bcl-2)protein expression but slightly increased Bcl-2-associated X protein(Bax)expression.Western blotting results revealed that HSP70 and Pgp expression levels were significantly increased following mild hypothermia.It was concluded that treatments of mild hyperthermia plus docetaxel inhibited the proliferation of human breast cancer cells,promoted apoptosis of breast cancer cells,and produced synergistic antitumor effects.
文摘This study aimed to evaluate the effects of Pin1 inhibitor Juglone on proliferation, migration and the angiogenic ability of breast cancer cell line MCF7 Adr. MCF7 Adr cells were cultured and separately treated with Pin1 inhibitor Juglone(treatment group) and DMEM without drug(control group). The cell cycle was examined by flow cytometry. Cell migration was measured by wound-healing assay. Cyclin E protein content was detected by Western blotting. The angiogenesis factor vascular endothelial growth factor(VEGF) in cell media was determined by enzyme linked immunosorbent assay. The results showed that the percentage of cells in G2/M phase in treatment group was significantly higher than that in control group(25.5% vs. 10.1%, P<0.05), and that in G0/G1 phase and S stage in treatment group was significantly lower than that in control group(40.5% vs. 48.2%, and 33.7% vs. 41.7%, P<0.05). Cyclin E protein content in treatment group was significantly lower than that in control group(39.2±7.4 vs. 100±23.1, P<0.05).(A0–A24)/A0 value in treatment group was significantly lower than that in control group(23.9±3.8 vs. 100±14.4, P<0.05). VEGF-A,-B, and-C contents in cell media of treatment group were significantly lower than those in control group(P<0.05). It was suggested that Pin1 inhibitor Juglone can effectively inhibit the proliferation, migration and the angiogenic ability of MCF7 Adr cells, and can be used as an alternative drug therapy for breast cancer.
基金supported by a grant from the NextGeneration BioGreen 21 Program(no.PJ011355-2015)supported by Priority Research Centers Program through NRF funded by the Ministry of Education,Science and Technology (2015R1A6A1A04020885)
文摘Bisphenol-A(BPA) has been considered as an endocrine disrupting chemical(EDC) because it can exert estrogenic properties.For bisphenol-S(BPS) and bisphenol-F(BPF) that are BPA analogs and substitutes,their risk to estrogendependent cancer has been reported rarely compared with the numerous cases of BPA.In this study,we examined whether BPA,BPS,and BPF can lead to the proliferation,migration,and epithelial mesenchymal transition(EMT) of MCF-7 clonal variant(MCF-7 CV) breast cancer cells expressing estrogen receptors(ERs).In a cell viability assay,BPA,BPS,and BPF significantly increased proliferation of MCF-7 CV cells compared to control(DMSO) as did17β-estradiol(E2).In Western blotting assay,BPA,BPS,and BPF enhanced the protein expression of cell cycle progression genes such as cyclin D1 and E1.In addition,MCF-7 CV cells lost cell to cell contacts and acquired fibroblast-like morphology by the treatment of BPA,BPS,or BPF for 24 hours.In cell migration assay,BPA,BPS,and BPF accelerated the migration capability of MCF-7 CV cells as did E2.In relation with the EMT process,BPA,BPS,and BPF increased the protein expression of N-cadherin,while they decreased the protein expression of Ecadherin.When BPA,BPS,and BPF were co-treated with ICI 182,780,an ER antagonist,proliferation effects were reversed,the expression of cyclin D1 and cyclin E1 was downregulated,and the altered cell migration and expression of N-cadherin and E-cadherin by BPA,BPS,and BPF were restored to the control level.Thus,these results imply that BPS and BPF also have the risk of breast cancer progression as much as BPA in the induction of proliferation and migration of MCF-7 CV cells by regulating the protein expression of cell cycle-related genes and EMT markers via the ER-dependent pathway.
