BACKGROUND Small cell lung cancer(SCLC)is a common and aggressive subtype of lung cancer.It is characterized by rapid growth and a high mortality rate.Approximately 10%of patients with SCLC present with brain metastas...BACKGROUND Small cell lung cancer(SCLC)is a common and aggressive subtype of lung cancer.It is characterized by rapid growth and a high mortality rate.Approximately 10%of patients with SCLC present with brain metastases at the time of diagnosis,which is associated with a median survival of 5 mo.This study aimed to summarize the effect of bevacizumab on the progression-free survival(PFS)and overall survival of patients with brain metastasis of SCLC.CASE SUMMARY A 62-year-old man was referred to our hospital in February 2023 because of dizziness and numbness of the right lower extremity without headache or fever for more than four weeks.The patient was diagnosed with limited-stage SCLC.He received 8 cycles of chemotherapy combined with maintenance bevacizumab therapy and achieved a PFS of over 7 mo.CONCLUSION The combination of bevacizumab and irinotecan effectively alleviated brain metastasis in SCLC and prolonged PFS.展开更多
The term“undruggable”is to describe molecules that are not targetable or at least hard to target pharmacologically.Unfortunately,some targets with potent oncogenic activity fall into this category,and currently litt...The term“undruggable”is to describe molecules that are not targetable or at least hard to target pharmacologically.Unfortunately,some targets with potent oncogenic activity fall into this category,and currently little is known about how to solve this problem,which largely hampered drug research on human cancers.Ras,as one of the most common oncogenes,was previously considered“undruggable”,but in recent years,a few small molecules like Sotorasib(AMG-510)have emerged and proved their targeted anti-cancer effects.Further,myc,as one of the most studied oncogenes,and tp53,being the most common tumor suppressor genes,are both considered“undruggable”.Many attempts have been made to target these“undruggable”targets,but little progress has been made yet.This article summarizes the current progress of direct and indirect targeting approaches for ras,myc,two oncogenes,and tp53,a tumor suppressor gene.These are potential therapeutic targets but are considered“undruggable”.We conclude with some emerging research approaches like proteolysis targeting chimeras(PROTACs),cancer vaccines,and artificial intelligence(AI)-based drug discovery,which might provide new cues for cancer intervention.Therefore,this review sets out to clarify the current status of targeted anti-cancer drug research,and the insights gained from this review may be of assistance to learn from experience and find new ideas in developing new chemicals that directly target such“undruggable”molecules.展开更多
[Objectives]To investigate the effects of propolis extract on HeLa cells to provide theoretical guidance for facilitating clinical treatment.[Methods]The effects of propolis on inflammation,and proliferation were anal...[Objectives]To investigate the effects of propolis extract on HeLa cells to provide theoretical guidance for facilitating clinical treatment.[Methods]The effects of propolis on inflammation,and proliferation were analyzed based on the levels of DNA transcriptional regulation and mRNA and protein expression levels.[Results]Propolis water extract(PWE)could inhibit the cell proliferation and production of DNA damage in a dosedependent manner.Moreover,the propolis water extract could significantly downregulate the expression of iNOS-Luc,PTGS-2-Luc,and IL-8-Luc,and that it was related to the expression of the NF-κB family protein.After the induction of HeLa cells by propolis,the expression of the cell cycle inhibitor gene p21 was increased,while that of the cell proliferation gene Ki67 was decreased.[Conclusions]Propolis water extract could significantly inhibit the cell proliferation and production of DNA damage,suggesting propolis as a potential candidate for the development of adjunctive therapy against cervical cancer.展开更多
Liver cancer is one of the most common causes of cancer death globally,and its incidence in the United States is increasing.Patients with advanced hepatocellular carcinoma(HCC)who are not candidates for surgical resec...Liver cancer is one of the most common causes of cancer death globally,and its incidence in the United States is increasing.Patients with advanced hepatocellular carcinoma(HCC)who are not candidates for surgical resection,liver transplant,or locoregional therapies can be treated with systemic therapies.Multiple agents,including sorafenib,lenvatinib,and regorafenib are approved for use as either first-or second-line therapy in this patient population,but all have relatively modest survival benefits.HCC is potentially susceptible to therapy with checkpoint inhibitors,including agents such as nivolumab and pembrolizumab,which are both approved by the Food and Drug Administration for patients previously treated with sorafenib but have not demonstrated superior overall survival in phase III trials.It is clear that more effective approaches are needed to potentiate the effects of checkpoint inhibitors in patients with HCC.This review will outline and appraise the current literature on the use of checkpoint inhibitors in HCC as part of a combination treatment involving an additional mode of therapy.The list of agents that can be paired with checkpoint inhibitors includes an additional checkpoint inhibitor,vascular endothelial growth factor or vascular endothelial growth factor receptor inhibitors,tyrosine kinase inhibitors,OX-40 agonists,and PT-112 inhibitors.The main non-pharmacologic therapies currently being studied for inclusion in a combination strategy include radiation therapy,trans-arterial chemoembolization,and ablation.展开更多
Tumorigenicity-inhibiting compounds have been identifled in our daily diet.For example,isothiocyanates(ITCs)found in cruciferous vegetables were reported to have potent cancer=prevention activities.The best characteri...Tumorigenicity-inhibiting compounds have been identifled in our daily diet.For example,isothiocyanates(ITCs)found in cruciferous vegetables were reported to have potent cancer=prevention activities.The best characterized ITC is sulforaphane(SF).SF can simultaneously modulate multiple cellular targets involved in carcinogenesis,including(1)modulating carcinogen-metabolizing enzymes and blocking the action of mutagens;(2)inhibition of cell proliferation and induction of apoptosis;and(3)inhibition of neo-angiogenesis and metastasis.SF targets cancer stem cells through modulation of nuclear factor kappa B(NF-κB),Sonic hedgehog(SHH),epithelial-mesenchymal transition,and Wnt/βcatenin pathways.Conventional chemotherapy/SF combination was tested in several studies and resulted in favorable outcomes.With its favorable toxicological profile,SF is a promising agent in cancer prevention and/or therapy.In this article,we discuss the human metabolism of SF and its effects on cancer prevention,treatment,and targeting cancer stem cells,as well as providing a brief review of recent human clinical trials on SF.展开更多
Objective: The current study evaluated various new colchicine analogs for their anticancer activity and to study the primary mechanism of apoptosis and in vivo antitumor activity of the analogs with selective anticanc...Objective: The current study evaluated various new colchicine analogs for their anticancer activity and to study the primary mechanism of apoptosis and in vivo antitumor activity of the analogs with selective anticancer properties and minimal toxicity to normal cells.Methods: Sulforhodamine B(SRB) assay was used to screen various colchicine analogs for their in vitro cytotoxicity. The effect of N-[(7S)-1,2,3-trimethoxy-9-oxo-10-(pyrrolidine-1-yl)5,6,7,9-tetrahydrobenzo[a] heptalene-7-yl] acetamide(ⅢM-067) on clonogenicity, apoptotic induction, and invasiveness of A549 cells was determined using a clonogenic assay, scratch assay, and staining with 4’,6-diamidino-2-phenylindole(DAPI) and annexin V/propidium iodide. Mitochondrial membrane potential(MMP) and reactive oxygen species(ROS) levels were observed using fluorescence microscopy. Western blot analysis was used to quantify expression of proteins involved in apoptosis, cell cycle, and phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR) signaling. Pharmacokinetic and in vivo efficacy studies against Ehrlich ascites carcinoma(EAC) and Ehrlich solid tumor models were conducted using Swiss albino mice.Results: ⅢM-067 showed potent cytotoxicity and better selectivity than all other colchicine analogs screened in this study. The selective activity of ⅢM-067 toward A549 cells was higher among other cancer cell lines,with a selectivity index(SI) value of 2.28. ⅢM-067 demonstrated concentration-and time-dependent cytotoxicity against A549 cells with half-maximal inhibitory concentration values of 0.207, 0.150 and0.106 μmol/L at 24, 48 and 72 h, respectively. It also had reduced toxicity to normal cells(SI > 1) than the parent compound colchicine(SI = 1). ⅢM-067 reduced the clonogenic ability of A549 cells in a dose-dependent manner. ⅢM-067 enhanced ROS production from 24.6% at 0.05 μmol/L to 82.1% at 0.4 μmol/L and substantially decreased the MMP(100% in control to 5.6% at 0.4 μmol/L). The annexin V-FITC assay demonstrated78% apoptosis at 0.4 μmol/L. ⅢM-067 significantly(P < 0.5) induced the expression of various intrinsic apoptotic pathway proteins, and it differentially regulated the PI3K/AKT/mTOR signaling pathway. Furthermore,ⅢM-067 exhibited remarkable in vivo anticancer activity against the murine EAC model, with tumor growth inhibition(TGI) of 67.0% at a dose of 6 mg/kg(i.p.) and a reduced mortality compared to colchicine. ⅢM-067also effectively inhibited the tumor growth in the murine solid tumor model with TGI rates of 48.10%, 55.68%and 44.00% at doses of 5 mg/kg(i.p.), 6 mg/kg(i.p.) and 7 mg/kg(p.o.), respectively.Conclusion: ⅢM-067 exhibited significant anticancer activity with reduced toxicity both in vitro and in vivo and is a promising anticancer candidate. However, further studies are required in clinical settings to fully understand its potential.展开更多
OBJECTIVE:To identify the active anti-tumor constituents in the extract from Danshen(Radix Salviae Miltiorrhizae) and investigate the mechanisms underlying the actions.METHODS:First,we introduced a two-step counter-cu...OBJECTIVE:To identify the active anti-tumor constituents in the extract from Danshen(Radix Salviae Miltiorrhizae) and investigate the mechanisms underlying the actions.METHODS:First,we introduced a two-step counter-current chromatography to extract the therapeutically active diterpenoid,tanshinone from Danshen(Radix Salviae Miltiorrhizae).The cholecystokinin(CCK-8) method was used to evaluate the inhibitory effect of diterpenoid tanshinone in liver cancer QGY-7703,lung cancer PC9,lung cancer A549,gastric cancer MKN-45,gastric cancer HGC-27,colon cancer HCT116,myeloma cell U266/RPMI8226,and human breast cancer MCF-7 in vitro.Fluorescence staining was used to observe the cytotoxicity ofditerpenoid tanshinone on PC9 cells.The Western blot was used to detect apoptosis-related protein poly ADP-ribose polymerase(PARP),cysteinyl aspartate specific proteinase3/9(caspase3/9),and cleaved-cysteinyl aspartate specific proteinase3/9(cleaved-caspase3/9).The endoplasmic reticulum stress-related activating transcription factor 4(ATF4),phosphorylated eukaryotic initiation factor 2α(p-e IF2α),and phosphorylated jun amino-terminal kinase(p-JNK),and caspase-12 were also analyzed using the Western blot.RESULTS:Diterpenoid tanshinone inhibited the nine human tumor cell lines,with an IC50 of4.37-29 μg/m L,with the PC9 and MCF-7 displaying the lowest values.Fluorescence staining showed a lethal effect of diterpenoid tanshinone on PC9 cells.The Western blot showed that the expression of caspase3/9 protein and ATF-4 protein decreased gradually.However,the PARP,cleaved-caspase 3/9and the expression of p-e IF2 α,P-JNK,and caspase-12 increased gradually,in a dose-dependent fashion.CONCLUSION:We successfully introduced a two-step counter-current chromatography method to extract diterpenoid tanshinone,and demonstrated its antitumor activity.Diterpenoid tanshinone can induce apoptosis in nine human cancer cell lines.展开更多
OBJECTIVE:To investigate the efficacy of the extract from Yiyuan Yiliu Tang(益元抑瘤汤,YYYLT)on human lung adenocarcinoma cells A549 and human hepatoma cells Bel7402.METHODS:The cancer cell lines were treated with var...OBJECTIVE:To investigate the efficacy of the extract from Yiyuan Yiliu Tang(益元抑瘤汤,YYYLT)on human lung adenocarcinoma cells A549 and human hepatoma cells Bel7402.METHODS:The cancer cell lines were treated with various concentrations(0,100,200,300,and400μg/m L)of the crude water extract of YYYLT and then cell viability,toxicity,cytokine secretion,and cell cycle/apoptosis were determined by MTT assay,LDH assay,and flow cytometry,respectively.RESULTS:The extract from YYYLT significantly suppressed the proliferation of the cancer cell lines and the release of interleukin-2 and tumor necrosis factor-αin a dose-dependent manner.The extract also promoted apoptosis,caused cell cycle arrest at G0/G1 phase,and increased the expression of caspase-3,B-cell lymphoma-2(Bcl-2),and Bcl-2-associated X proteins.CONCLUSION:The extract from YYYLT might be a potential treatment for human lung and liver cancers.展开更多
OBJECTIVE:To further clarify the anticancer mechanisms of Liujunzi decoction(六君子汤)and provide possible targets for the treatment of advanced-stage nonsmall cell lung cancer(NSCLC)by re-analyzing differential gene ...OBJECTIVE:To further clarify the anticancer mechanisms of Liujunzi decoction(六君子汤)and provide possible targets for the treatment of advanced-stage nonsmall cell lung cancer(NSCLC)by re-analyzing differential gene expression profile of peripheral blood mononuclear cells(PBMCs)from Liujunzi decoctiontreated NSCLC patients receiving first-line chemotherapy.METHODS:The PBMC gene expression microarray data set GSE61926 was retrieved from a high throughput gene expression database.Differentially expressed genes(DEGs)were screened by paired sample t-test and the multiple ratio method.Gene ontology and Kyoto encyclopedia of genes and genomes(KEGG)pathway analyses were performed using the DAVID database.The protein–protein interaction(PPI)network was constructed using interaction gene library retrieval tools and Cytoscape software.RESULTS:A total of 162 DEGs were identified,with 67 upregulated genes and 95 downregulated genes.The functional distribution of Gene Oncology(GO)genes showed that DEGs were mostly concentrated in extracellular regions,calcium ion binding,and transcriptase activity.KEGG pathway analysis showed that cytokine–cytokine receptor interactions were significantly enriched.PPI network analysis screened out the top 10 central protein-coding genes with the highest nodal degree:IL2,PIWIL4,DICER1,PIWIL2,SAA1,XCL1,IL22RA1,ARHGAP11A,DCP1A,and GDNF.Among them,the central protein-coding gene with the highest node degree was IL2.In addition,the central protein-coding genes with high node degrees and high molecular complex detection(MCODE)scores were PIWIL4,DICER1,PIWIL2,and DCP1A,all of which are related to tumor development.CONCLUSIONS:One signaling pathway and 10 central protein-coding genes related to anticancer mechanisms were screened by re-analysis of GSE61926 data.IL2,PIWIL4,DICER1,PIWIL2,and DCP1 A may have important roles in the mechanism of Liujunzi decoction treatment against NSCLC.Our results suggest that the anticancer mechanism of Liujunzi decoction may be related to gene silencing by RNA and the biological processes of piwi-interacting RNA and other small RNAs.展开更多
OBJECTIVE:To conduct an ethnobotanical survey and document the traditional anticancer and antidiabetic plants used by the local tribes of Mizoram,Northeast India.METHODS:A systematic survey was conducted in rural and ...OBJECTIVE:To conduct an ethnobotanical survey and document the traditional anticancer and antidiabetic plants used by the local tribes of Mizoram,Northeast India.METHODS:A systematic survey was conducted in rural and urban areas of Mizoram by interviewing traditional practitioners,and cancer and diabetes patients.A detailed literature search was carried out using MEDLINE and SCOPUS and available literatures were selected and included in the study.The use value(UV)of the selected plants was calculated based on the number of citations per species given by informants.RESULTS:Data was obtained for 201 traditional medicinal plants from Mizoram,Northeast India.These plants were from 72 different families and belonged to 140 genera.Of these,103 plants were reported for the first time as possessing either anticancer or antidiabetic potential,and 105 plants were identified that were used for the treatment of both diseases.Three plants(Phlogacanthus thysiformis,Solanum gilo and Lobelia angulata)with antidiabetic potential,and six plants(Dillenia scabrella,Circium sinesis,Eupatorium nodiflorum,Pratia begonifolia,Vernonia teres and Plantago erosa)with both as anticancer and antidiabetic potential were documented for the first time.CONCLUSION:In this study,we documented several explored and unexplored medicinal plants that may be useful for the management of cancer and diabetes.This study suggests that there is a broad scope fordeveloping potent anticancer and antidiabetic agent from the flora of Mizoram,Northeast India.展开更多
OBJECTIVE: To explore the total phenolic and flavonoid content, enzymatic, non-enzymatic antioxidant properties, anti-inflammation and anticancer activities of hexane, ethyl acetate and methanol extracts of Floscopa s...OBJECTIVE: To explore the total phenolic and flavonoid content, enzymatic, non-enzymatic antioxidant properties, anti-inflammation and anticancer activities of hexane, ethyl acetate and methanol extracts of Floscopa scandens(F. scandens).METHODS: Non-enzymatic antioxidant activity was examined by 2, 2-diphenyl-1-picrylhydrazyl assay, nitric oxide scavenging assay, hydroxyl radical scavenging assay, reducing power assay, hydrogen peroxide scavenging assay, superoxide scavenging assay and metal chelating assay. Enzymatic antioxidant ability was screened for the antioxidant enzymes such as ascorbate oxidase, peroxidase, catalase and polyphenol oxidase. The anti-inflammatory property was proved with the inhibition of protein denaturation and protease inhibitory assays. In vitro anticancer activity was assessed by cell viability assay.RESULTS: Methanol extract contained high amount of phenols(198.41 mg catechol equivalent/gram extract) and flavonoids(101.70 mg quercetin equivalent/gram extract) showed higher activity than hexane and ethyl acetate extracts in all experiments. Fresh plant showed considerable enzymatic antioxidant activity.CONCLUSION: The results revealed that the methanol extracts of F. scandens could be used as a potential source of antioxidant, anti-inflammatory and anticancer bioactive compounds.展开更多
基金Yu-Qing Xia Famous Old Chinese Medicine Heritage Workshop of“3+3”Project of Traditional Chinese Medicine Heritage in Beijing,Jing Zhong Yi Ke Zi(2021),No.73National Natural Science Foundation of China,No.81973640+1 种基金Nursery Program of Wangjing Hospital,Chinese Academy of Traditional Chinese Medicine,No.WJYY-YJKT-2022-05China Academy of Traditional Chinese Medicine Wangjing Hospital High-Level Chinese Medicine Hospital Construction Project Chinese Medicine Clinical Evidence-Based Research:The Evidence-Based Research of Electrothermal Acupuncture for Relieving Cancer-Related Fatigue in Patients With Malignant Tumor,No.WYYY-XZKT-2023-20.
文摘BACKGROUND Small cell lung cancer(SCLC)is a common and aggressive subtype of lung cancer.It is characterized by rapid growth and a high mortality rate.Approximately 10%of patients with SCLC present with brain metastases at the time of diagnosis,which is associated with a median survival of 5 mo.This study aimed to summarize the effect of bevacizumab on the progression-free survival(PFS)and overall survival of patients with brain metastasis of SCLC.CASE SUMMARY A 62-year-old man was referred to our hospital in February 2023 because of dizziness and numbness of the right lower extremity without headache or fever for more than four weeks.The patient was diagnosed with limited-stage SCLC.He received 8 cycles of chemotherapy combined with maintenance bevacizumab therapy and achieved a PFS of over 7 mo.CONCLUSION The combination of bevacizumab and irinotecan effectively alleviated brain metastasis in SCLC and prolonged PFS.
基金supported by Grants from the National Natural Science Foundation of China(81902784)the CAMS Innovation Fund for Medical Sciences(CIFMS,2019-I2M-5-004)+2 种基金the Fund of Sichuan Provincial Department of Science and Technology(2022YFSY0058)the Research Funding(RCDWJS 2020-20)the Research and Development Program(RD-02-202002)from West China School/Hospital of Stomatology Sichuan University.
文摘The term“undruggable”is to describe molecules that are not targetable or at least hard to target pharmacologically.Unfortunately,some targets with potent oncogenic activity fall into this category,and currently little is known about how to solve this problem,which largely hampered drug research on human cancers.Ras,as one of the most common oncogenes,was previously considered“undruggable”,but in recent years,a few small molecules like Sotorasib(AMG-510)have emerged and proved their targeted anti-cancer effects.Further,myc,as one of the most studied oncogenes,and tp53,being the most common tumor suppressor genes,are both considered“undruggable”.Many attempts have been made to target these“undruggable”targets,but little progress has been made yet.This article summarizes the current progress of direct and indirect targeting approaches for ras,myc,two oncogenes,and tp53,a tumor suppressor gene.These are potential therapeutic targets but are considered“undruggable”.We conclude with some emerging research approaches like proteolysis targeting chimeras(PROTACs),cancer vaccines,and artificial intelligence(AI)-based drug discovery,which might provide new cues for cancer intervention.Therefore,this review sets out to clarify the current status of targeted anti-cancer drug research,and the insights gained from this review may be of assistance to learn from experience and find new ideas in developing new chemicals that directly target such“undruggable”molecules.
基金Supported by the Modern Agricultural Technology Industry System of ShandongProvince(SDAIT-24-05)。
文摘[Objectives]To investigate the effects of propolis extract on HeLa cells to provide theoretical guidance for facilitating clinical treatment.[Methods]The effects of propolis on inflammation,and proliferation were analyzed based on the levels of DNA transcriptional regulation and mRNA and protein expression levels.[Results]Propolis water extract(PWE)could inhibit the cell proliferation and production of DNA damage in a dosedependent manner.Moreover,the propolis water extract could significantly downregulate the expression of iNOS-Luc,PTGS-2-Luc,and IL-8-Luc,and that it was related to the expression of the NF-κB family protein.After the induction of HeLa cells by propolis,the expression of the cell cycle inhibitor gene p21 was increased,while that of the cell proliferation gene Ki67 was decreased.[Conclusions]Propolis water extract could significantly inhibit the cell proliferation and production of DNA damage,suggesting propolis as a potential candidate for the development of adjunctive therapy against cervical cancer.
文摘Liver cancer is one of the most common causes of cancer death globally,and its incidence in the United States is increasing.Patients with advanced hepatocellular carcinoma(HCC)who are not candidates for surgical resection,liver transplant,or locoregional therapies can be treated with systemic therapies.Multiple agents,including sorafenib,lenvatinib,and regorafenib are approved for use as either first-or second-line therapy in this patient population,but all have relatively modest survival benefits.HCC is potentially susceptible to therapy with checkpoint inhibitors,including agents such as nivolumab and pembrolizumab,which are both approved by the Food and Drug Administration for patients previously treated with sorafenib but have not demonstrated superior overall survival in phase III trials.It is clear that more effective approaches are needed to potentiate the effects of checkpoint inhibitors in patients with HCC.This review will outline and appraise the current literature on the use of checkpoint inhibitors in HCC as part of a combination treatment involving an additional mode of therapy.The list of agents that can be paired with checkpoint inhibitors includes an additional checkpoint inhibitor,vascular endothelial growth factor or vascular endothelial growth factor receptor inhibitors,tyrosine kinase inhibitors,OX-40 agonists,and PT-112 inhibitors.The main non-pharmacologic therapies currently being studied for inclusion in a combination strategy include radiation therapy,trans-arterial chemoembolization,and ablation.
文摘Tumorigenicity-inhibiting compounds have been identifled in our daily diet.For example,isothiocyanates(ITCs)found in cruciferous vegetables were reported to have potent cancer=prevention activities.The best characterized ITC is sulforaphane(SF).SF can simultaneously modulate multiple cellular targets involved in carcinogenesis,including(1)modulating carcinogen-metabolizing enzymes and blocking the action of mutagens;(2)inhibition of cell proliferation and induction of apoptosis;and(3)inhibition of neo-angiogenesis and metastasis.SF targets cancer stem cells through modulation of nuclear factor kappa B(NF-κB),Sonic hedgehog(SHH),epithelial-mesenchymal transition,and Wnt/βcatenin pathways.Conventional chemotherapy/SF combination was tested in several studies and resulted in favorable outcomes.With its favorable toxicological profile,SF is a promising agent in cancer prevention and/or therapy.In this article,we discuss the human metabolism of SF and its effects on cancer prevention,treatment,and targeting cancer stem cells,as well as providing a brief review of recent human clinical trials on SF.
基金Sumera Malik acknowledges the University Grants Commission for senior research fellowship(GAP-1128)Dr.Sanket K.Shukla acknowledges the SERB-DST for Ramanujan Fellowship(SB/S2/RJN-078/2019)and project(GAP-2194).
文摘Objective: The current study evaluated various new colchicine analogs for their anticancer activity and to study the primary mechanism of apoptosis and in vivo antitumor activity of the analogs with selective anticancer properties and minimal toxicity to normal cells.Methods: Sulforhodamine B(SRB) assay was used to screen various colchicine analogs for their in vitro cytotoxicity. The effect of N-[(7S)-1,2,3-trimethoxy-9-oxo-10-(pyrrolidine-1-yl)5,6,7,9-tetrahydrobenzo[a] heptalene-7-yl] acetamide(ⅢM-067) on clonogenicity, apoptotic induction, and invasiveness of A549 cells was determined using a clonogenic assay, scratch assay, and staining with 4’,6-diamidino-2-phenylindole(DAPI) and annexin V/propidium iodide. Mitochondrial membrane potential(MMP) and reactive oxygen species(ROS) levels were observed using fluorescence microscopy. Western blot analysis was used to quantify expression of proteins involved in apoptosis, cell cycle, and phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR) signaling. Pharmacokinetic and in vivo efficacy studies against Ehrlich ascites carcinoma(EAC) and Ehrlich solid tumor models were conducted using Swiss albino mice.Results: ⅢM-067 showed potent cytotoxicity and better selectivity than all other colchicine analogs screened in this study. The selective activity of ⅢM-067 toward A549 cells was higher among other cancer cell lines,with a selectivity index(SI) value of 2.28. ⅢM-067 demonstrated concentration-and time-dependent cytotoxicity against A549 cells with half-maximal inhibitory concentration values of 0.207, 0.150 and0.106 μmol/L at 24, 48 and 72 h, respectively. It also had reduced toxicity to normal cells(SI > 1) than the parent compound colchicine(SI = 1). ⅢM-067 reduced the clonogenic ability of A549 cells in a dose-dependent manner. ⅢM-067 enhanced ROS production from 24.6% at 0.05 μmol/L to 82.1% at 0.4 μmol/L and substantially decreased the MMP(100% in control to 5.6% at 0.4 μmol/L). The annexin V-FITC assay demonstrated78% apoptosis at 0.4 μmol/L. ⅢM-067 significantly(P < 0.5) induced the expression of various intrinsic apoptotic pathway proteins, and it differentially regulated the PI3K/AKT/mTOR signaling pathway. Furthermore,ⅢM-067 exhibited remarkable in vivo anticancer activity against the murine EAC model, with tumor growth inhibition(TGI) of 67.0% at a dose of 6 mg/kg(i.p.) and a reduced mortality compared to colchicine. ⅢM-067also effectively inhibited the tumor growth in the murine solid tumor model with TGI rates of 48.10%, 55.68%and 44.00% at doses of 5 mg/kg(i.p.), 6 mg/kg(i.p.) and 7 mg/kg(p.o.), respectively.Conclusion: ⅢM-067 exhibited significant anticancer activity with reduced toxicity both in vitro and in vivo and is a promising anticancer candidate. However, further studies are required in clinical settings to fully understand its potential.
基金Supported by Key Projects of Zhejiang Province Science and Technology(Arsenic Trioxide Injection Associate with Tanshinone Treat the Hepatocarcinoma of Qi-Stagnancy and Blood Stasis,No.2012C13017-1)the Specialized Research Foundation for the Doctoral Program of Higher Education of China(the Mechanism of Jak-STAT3 Signaling Transduction in Anti-Hepatocarcinoma Associated with Arsenic Trioxide and Cryptotanshinone,No.20123322110001)
文摘OBJECTIVE:To identify the active anti-tumor constituents in the extract from Danshen(Radix Salviae Miltiorrhizae) and investigate the mechanisms underlying the actions.METHODS:First,we introduced a two-step counter-current chromatography to extract the therapeutically active diterpenoid,tanshinone from Danshen(Radix Salviae Miltiorrhizae).The cholecystokinin(CCK-8) method was used to evaluate the inhibitory effect of diterpenoid tanshinone in liver cancer QGY-7703,lung cancer PC9,lung cancer A549,gastric cancer MKN-45,gastric cancer HGC-27,colon cancer HCT116,myeloma cell U266/RPMI8226,and human breast cancer MCF-7 in vitro.Fluorescence staining was used to observe the cytotoxicity ofditerpenoid tanshinone on PC9 cells.The Western blot was used to detect apoptosis-related protein poly ADP-ribose polymerase(PARP),cysteinyl aspartate specific proteinase3/9(caspase3/9),and cleaved-cysteinyl aspartate specific proteinase3/9(cleaved-caspase3/9).The endoplasmic reticulum stress-related activating transcription factor 4(ATF4),phosphorylated eukaryotic initiation factor 2α(p-e IF2α),and phosphorylated jun amino-terminal kinase(p-JNK),and caspase-12 were also analyzed using the Western blot.RESULTS:Diterpenoid tanshinone inhibited the nine human tumor cell lines,with an IC50 of4.37-29 μg/m L,with the PC9 and MCF-7 displaying the lowest values.Fluorescence staining showed a lethal effect of diterpenoid tanshinone on PC9 cells.The Western blot showed that the expression of caspase3/9 protein and ATF-4 protein decreased gradually.However,the PARP,cleaved-caspase 3/9and the expression of p-e IF2 α,P-JNK,and caspase-12 increased gradually,in a dose-dependent fashion.CONCLUSION:We successfully introduced a two-step counter-current chromatography method to extract diterpenoid tanshinone,and demonstrated its antitumor activity.Diterpenoid tanshinone can induce apoptosis in nine human cancer cell lines.
基金Supported by Institutional Funding(No.JDKW-2020-0013,the Nature Science Foundation of Jiading District,ShanghaiNo.2020-ZD-03,the Key Projects of Jiading District Health Commission,Shanghai+1 种基金No.JDKW-2018-W21,the Agricultural and Social Research Projects of Jiading,Shanghaiand No.2020-KY-14,the General project of Jiading District Health Commission,Shanghai)。
文摘OBJECTIVE:To investigate the efficacy of the extract from Yiyuan Yiliu Tang(益元抑瘤汤,YYYLT)on human lung adenocarcinoma cells A549 and human hepatoma cells Bel7402.METHODS:The cancer cell lines were treated with various concentrations(0,100,200,300,and400μg/m L)of the crude water extract of YYYLT and then cell viability,toxicity,cytokine secretion,and cell cycle/apoptosis were determined by MTT assay,LDH assay,and flow cytometry,respectively.RESULTS:The extract from YYYLT significantly suppressed the proliferation of the cancer cell lines and the release of interleukin-2 and tumor necrosis factor-αin a dose-dependent manner.The extract also promoted apoptosis,caused cell cycle arrest at G0/G1 phase,and increased the expression of caspase-3,B-cell lymphoma-2(Bcl-2),and Bcl-2-associated X proteins.CONCLUSION:The extract from YYYLT might be a potential treatment for human lung and liver cancers.
基金Supported by the National Natural Science Foundation of China(NSFC)(81903270)(Therapeutic Effect and Mechanism of Embryonic Lung Progenitor Cell Transplantation on Silicosis Fibrosis)and(81703987)(Study on the Synergistic Effect and Mechanism of Yiqi Yangyin Jiedu Prescription Combined with Anti-CTLA-4 Mab in Inducing Anti-Lung Cancer Immune Response)Jinan Science and Technology Project(201907019)(Study of Therapy and Mechanisms of Embryonic Lung Stem Cell Transplantation on Silicosis Fibrosis)+4 种基金the Shanghai Science and Technology Commission(19401971200)(a Multicenter Randomized Controlled Study on Improving Prognosis of Patients With StageⅢA Non-Small Cell Lung Cancer By Liu Jiaxiang's Prescription for Qi-Yin Differentiation and Treatment)the Emerging Frontier Technology Joint Research Project of Shanghai Shenkang Hospital Development Center(SHDC12018131)(a Multicenter Randomized Controlled Double-Blind Study on the Prevention and Treatment of Postoperative Recurrence and Metastasis Of StageⅢA Non-Small Cell Lung Cancer By Liu Jiaxiang Qi-Yin Differentiation Method)the Major Project of Scientific Research and Innovation Plan of Shanghai Education Commission(No.2017-01-07-00-10-E00064)(Study on the Mechanism of Feyanning Prescription Against Lung Cancer Growth and Metastasis Derived from Jingqi Theory)Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine(AJ-37)(Clinical Study of Yiqi Yangyin Jiedu Prescription Combined With Oxitinib in the Treatment of Advanced Lung Cancer With T790M Mutation)and(AJ-41)(Clinical Study of“Decubitus Chiropractic Therapy”in the Treatment of Vertebral Artery Type Cervical Spondylosis)National Traditional Chinese Medicine Clinical Research Base Long-Yi-Xue-Zhe Nurturing Plan(LYTD-64)(Mechanism of Reversal of EGFR-Tkis Resistance Induced By HGF in Tumor-Bearing H1975-SCID Mice Based on Huachansu Injection)。
文摘OBJECTIVE:To further clarify the anticancer mechanisms of Liujunzi decoction(六君子汤)and provide possible targets for the treatment of advanced-stage nonsmall cell lung cancer(NSCLC)by re-analyzing differential gene expression profile of peripheral blood mononuclear cells(PBMCs)from Liujunzi decoctiontreated NSCLC patients receiving first-line chemotherapy.METHODS:The PBMC gene expression microarray data set GSE61926 was retrieved from a high throughput gene expression database.Differentially expressed genes(DEGs)were screened by paired sample t-test and the multiple ratio method.Gene ontology and Kyoto encyclopedia of genes and genomes(KEGG)pathway analyses were performed using the DAVID database.The protein–protein interaction(PPI)network was constructed using interaction gene library retrieval tools and Cytoscape software.RESULTS:A total of 162 DEGs were identified,with 67 upregulated genes and 95 downregulated genes.The functional distribution of Gene Oncology(GO)genes showed that DEGs were mostly concentrated in extracellular regions,calcium ion binding,and transcriptase activity.KEGG pathway analysis showed that cytokine–cytokine receptor interactions were significantly enriched.PPI network analysis screened out the top 10 central protein-coding genes with the highest nodal degree:IL2,PIWIL4,DICER1,PIWIL2,SAA1,XCL1,IL22RA1,ARHGAP11A,DCP1A,and GDNF.Among them,the central protein-coding gene with the highest node degree was IL2.In addition,the central protein-coding genes with high node degrees and high molecular complex detection(MCODE)scores were PIWIL4,DICER1,PIWIL2,and DCP1A,all of which are related to tumor development.CONCLUSIONS:One signaling pathway and 10 central protein-coding genes related to anticancer mechanisms were screened by re-analysis of GSE61926 data.IL2,PIWIL4,DICER1,PIWIL2,and DCP1 A may have important roles in the mechanism of Liujunzi decoction treatment against NSCLC.Our results suggest that the anticancer mechanism of Liujunzi decoction may be related to gene silencing by RNA and the biological processes of piwi-interacting RNA and other small RNAs.
基金Supported by the University Grants Commision(UGC)New Delhi for providing fellowship under Rajiv Gandhi National Fellowship(F1-17.1/2015-16/RGNF-2015-17-SC-UTT-9023)。
文摘OBJECTIVE:To conduct an ethnobotanical survey and document the traditional anticancer and antidiabetic plants used by the local tribes of Mizoram,Northeast India.METHODS:A systematic survey was conducted in rural and urban areas of Mizoram by interviewing traditional practitioners,and cancer and diabetes patients.A detailed literature search was carried out using MEDLINE and SCOPUS and available literatures were selected and included in the study.The use value(UV)of the selected plants was calculated based on the number of citations per species given by informants.RESULTS:Data was obtained for 201 traditional medicinal plants from Mizoram,Northeast India.These plants were from 72 different families and belonged to 140 genera.Of these,103 plants were reported for the first time as possessing either anticancer or antidiabetic potential,and 105 plants were identified that were used for the treatment of both diseases.Three plants(Phlogacanthus thysiformis,Solanum gilo and Lobelia angulata)with antidiabetic potential,and six plants(Dillenia scabrella,Circium sinesis,Eupatorium nodiflorum,Pratia begonifolia,Vernonia teres and Plantago erosa)with both as anticancer and antidiabetic potential were documented for the first time.CONCLUSION:In this study,we documented several explored and unexplored medicinal plants that may be useful for the management of cancer and diabetes.This study suggests that there is a broad scope fordeveloping potent anticancer and antidiabetic agent from the flora of Mizoram,Northeast India.
文摘OBJECTIVE: To explore the total phenolic and flavonoid content, enzymatic, non-enzymatic antioxidant properties, anti-inflammation and anticancer activities of hexane, ethyl acetate and methanol extracts of Floscopa scandens(F. scandens).METHODS: Non-enzymatic antioxidant activity was examined by 2, 2-diphenyl-1-picrylhydrazyl assay, nitric oxide scavenging assay, hydroxyl radical scavenging assay, reducing power assay, hydrogen peroxide scavenging assay, superoxide scavenging assay and metal chelating assay. Enzymatic antioxidant ability was screened for the antioxidant enzymes such as ascorbate oxidase, peroxidase, catalase and polyphenol oxidase. The anti-inflammatory property was proved with the inhibition of protein denaturation and protease inhibitory assays. In vitro anticancer activity was assessed by cell viability assay.RESULTS: Methanol extract contained high amount of phenols(198.41 mg catechol equivalent/gram extract) and flavonoids(101.70 mg quercetin equivalent/gram extract) showed higher activity than hexane and ethyl acetate extracts in all experiments. Fresh plant showed considerable enzymatic antioxidant activity.CONCLUSION: The results revealed that the methanol extracts of F. scandens could be used as a potential source of antioxidant, anti-inflammatory and anticancer bioactive compounds.
