BACKGROUND The demand for the development of cancer nanomedicine has increased due to its great therapeutic value that can overcome the limitations of conventional cancer therapy.However,the presence of various bioact...BACKGROUND The demand for the development of cancer nanomedicine has increased due to its great therapeutic value that can overcome the limitations of conventional cancer therapy.However,the presence of various bioactive compounds in crude plant extracts used for the synthesis of silver nanoparticles(AgNPs)makes its precise mechanisms of action unclear.AIM To assessed the mRNA transcriptome profiling of human HepG2 cells exposed to Catharanthus roseus G.Don(C.roseus)-AgNPs.METHODS The proliferative activity of hepatocellular carcinoma(HepG2)and normal human liver(THLE3)cells treated with C.roseusAgNPs were measured using MTT assay.The RNA samples were extracted and sequenced using BGIseq500 platform.This is followed by data filtering,mapping,gene expression analysis,differentially expression genes analysis,Gene Ontology analysis,and pathway analysis.RESULTS The mean IC 50 values of C.roseusAgNPs on HepG2 was 4.38±1.59μg/mL while on THLE3 cells was 800±1.55μg/mL.Transcriptome profiling revealed an alteration of 296 genes.C.roseusAgNPs induced the expression of stress-associated genes such as MT,HSP and HMOX-1.Cellular signalling pathways were potentially activated through MAPK,TNF and TGF pathways that are responsible for apoptosis and cell cycle arrest.The alteration of ARF6,EHD2,FGFR3,RhoA,EEA1,VPS28,VPS25,and TSG101 indicated the uptake of C.roseus-AgNPs via both clathrin-dependent and clathrinindependent endocytosis.CONCLUSION This study provides new insights into gene expression study of biosynthesised AgNPs on cancer cells.The cytotoxicity effect is mediated by the aberrant gene alteration,and more interestingly the unique selective antiproliferative properties indicate the C.roseusAgNPs as an ideal anticancer candidate.展开更多
Objective: To evaluate the antioxidant and antiproliferative effect of methanolic bee pollen extract(BPE) of Malaysian stingless bee [Lepidotrigona terminata(L. terminata)]and its synergistic effect with cisplatin(a c...Objective: To evaluate the antioxidant and antiproliferative effect of methanolic bee pollen extract(BPE) of Malaysian stingless bee [Lepidotrigona terminata(L. terminata)]and its synergistic effect with cisplatin(a chemotherapeutic drug) on MCF-7 cancer cell line.Methods: The antioxidant activity of BPE from L. terminata was measured by using1,1-diphenyl-2-picrylhydrazyl radical(DPPH) assay. Antiproliferative activity at different concentrations of BPE and cisplatin was determined through using MTT assay on MCF-7 and L929 cell lines. An interaction effect(synergistic, additive and antagonistic) between BPE and cisplatin was determined by Compu Syn software based on MTT assay data.Results: The EC50(50% decrement of DPPH inhibition) of BPE was 0.5 mg/m L.L. terminata BPE exhibited antiproliferative activity on both cancer and normal cell lines.The IC50(concentration of drug that was required for 50% of cell inhibition in vitro) of BPE on MCF-7 was 15 mg/m L whereas in normal cell line L929 was 26 mg/m L. The IC50 for cisplatin on MCF-7 was 20 mmol/L. The combination effect of BPE and cisplatin on MCF-7 cells showed that BPE at 15 mg/m L was able to potentiate the inhibitory effect of cisplatin at all different concentrations(2.5–20.0 mg/m L). The average of cancer cells inhibition which was potentiated by BPE was around 50%. A combination index values of less than 1 reported in the Compu Syn software further proved the synergistic effect between BPE and cisplatin, suggesting that BPE was working synergistically with cisplatin.Conclusions: Our study therefore suggested that BPE of Malaysian stingless bee,L. terminata is a potential chemopreventive agent and can be used as a supplementary treatment for chemotherapy drugs. BPE might be able to be used to potentiate the effect of chemotherapy drugs with the possibility to reduce the required dose of the drugs. The molecular mechanisms of how the BPE exerts antiproliferative activity will be a much interesting area to look for in future studies.展开更多
基金Fundamental Research Grant Scheme from the Malaysian Ministry of Higher Education,No.FRGS/1/2015/SG03/USM/03/1。
文摘BACKGROUND The demand for the development of cancer nanomedicine has increased due to its great therapeutic value that can overcome the limitations of conventional cancer therapy.However,the presence of various bioactive compounds in crude plant extracts used for the synthesis of silver nanoparticles(AgNPs)makes its precise mechanisms of action unclear.AIM To assessed the mRNA transcriptome profiling of human HepG2 cells exposed to Catharanthus roseus G.Don(C.roseus)-AgNPs.METHODS The proliferative activity of hepatocellular carcinoma(HepG2)and normal human liver(THLE3)cells treated with C.roseusAgNPs were measured using MTT assay.The RNA samples were extracted and sequenced using BGIseq500 platform.This is followed by data filtering,mapping,gene expression analysis,differentially expression genes analysis,Gene Ontology analysis,and pathway analysis.RESULTS The mean IC 50 values of C.roseusAgNPs on HepG2 was 4.38±1.59μg/mL while on THLE3 cells was 800±1.55μg/mL.Transcriptome profiling revealed an alteration of 296 genes.C.roseusAgNPs induced the expression of stress-associated genes such as MT,HSP and HMOX-1.Cellular signalling pathways were potentially activated through MAPK,TNF and TGF pathways that are responsible for apoptosis and cell cycle arrest.The alteration of ARF6,EHD2,FGFR3,RhoA,EEA1,VPS28,VPS25,and TSG101 indicated the uptake of C.roseus-AgNPs via both clathrin-dependent and clathrinindependent endocytosis.CONCLUSION This study provides new insights into gene expression study of biosynthesised AgNPs on cancer cells.The cytotoxicity effect is mediated by the aberrant gene alteration,and more interestingly the unique selective antiproliferative properties indicate the C.roseusAgNPs as an ideal anticancer candidate.
基金Supported by Fundamental Research Grant Scheme,Ministry of Education Malaysia(Grant No:FRGS/2/2013/SKK01/USM/03/3)
文摘Objective: To evaluate the antioxidant and antiproliferative effect of methanolic bee pollen extract(BPE) of Malaysian stingless bee [Lepidotrigona terminata(L. terminata)]and its synergistic effect with cisplatin(a chemotherapeutic drug) on MCF-7 cancer cell line.Methods: The antioxidant activity of BPE from L. terminata was measured by using1,1-diphenyl-2-picrylhydrazyl radical(DPPH) assay. Antiproliferative activity at different concentrations of BPE and cisplatin was determined through using MTT assay on MCF-7 and L929 cell lines. An interaction effect(synergistic, additive and antagonistic) between BPE and cisplatin was determined by Compu Syn software based on MTT assay data.Results: The EC50(50% decrement of DPPH inhibition) of BPE was 0.5 mg/m L.L. terminata BPE exhibited antiproliferative activity on both cancer and normal cell lines.The IC50(concentration of drug that was required for 50% of cell inhibition in vitro) of BPE on MCF-7 was 15 mg/m L whereas in normal cell line L929 was 26 mg/m L. The IC50 for cisplatin on MCF-7 was 20 mmol/L. The combination effect of BPE and cisplatin on MCF-7 cells showed that BPE at 15 mg/m L was able to potentiate the inhibitory effect of cisplatin at all different concentrations(2.5–20.0 mg/m L). The average of cancer cells inhibition which was potentiated by BPE was around 50%. A combination index values of less than 1 reported in the Compu Syn software further proved the synergistic effect between BPE and cisplatin, suggesting that BPE was working synergistically with cisplatin.Conclusions: Our study therefore suggested that BPE of Malaysian stingless bee,L. terminata is a potential chemopreventive agent and can be used as a supplementary treatment for chemotherapy drugs. BPE might be able to be used to potentiate the effect of chemotherapy drugs with the possibility to reduce the required dose of the drugs. The molecular mechanisms of how the BPE exerts antiproliferative activity will be a much interesting area to look for in future studies.
