Objective:To evaluate of hesperidin to overcome resistance of doxorubicin in MCF-7 resistant doxorubicin cells(MCF-7/Dox)in cytotoxicity apoptosis and P-glycoprotein(Pgp)expression in combination with doxorubicin.Meth...Objective:To evaluate of hesperidin to overcome resistance of doxorubicin in MCF-7 resistant doxorubicin cells(MCF-7/Dox)in cytotoxicity apoptosis and P-glycoprotein(Pgp)expression in combination with doxorubicin.Methods:The cytotoxic properties.50%inhibition concentration(IC_(50))and its combination with doxorubicin in MCF-7 cell lines resistant to doxorubicin(MCF-7/Dox)cells were determined using MTT assay.Apoptosis induction was examined by double staining assay using ethidium bromide-acridine orange.Immunocytochemistry assay was performed to determine the level and localization of Pgp.Results:Single treatment of hesperidin showed cytotoxic activity on MCF-7/Dox cells with IC_(50)value of 11μmol/L.Thus,combination treatment from hesperidin and doxorubicin showed addictive and antagonist effect(CI>1.0).Hesperidin did not increase the apoptotic induction,but decreased the Pgp expressions level when combined with doxorubicin in low concentration.Conclusions:Hesperidin has cytotoxic effect on MCF-7/Dox cells with IC_(50)of 11μmol/L.Hesperidin did not increased the apoptotic induction combined with doxorubicin.Cochemotherapy application of doxorubicin and hesperidin on MCF-7/Dox cells showed synergism effect through inhibition of Pgp expression.展开更多
Multidrug resistance （MDR） in tumor cells can reduce the efficacy of chemotherapy. Overexpression of transporters is an important mechanism for MDR. P-glycoprotein （P-gp） is an ATP-binding cassette transporter fre...Multidrug resistance （MDR） in tumor cells can reduce the efficacy of chemotherapy. Overexpression of transporters is an important mechanism for MDR. P-glycoprotein （P-gp） is an ATP-binding cassette transporter frequently expressed in multidrug resistant tumor cells, inducing MDR. To reverse P-gp dependent MDR, anticancer drugs can be administered with P-gp inhibitors. Piperine and （R）-（＋）-citronellal both are P-gp inhibitors from dietary sources. In the present study, we aimed to evaluate the MDR reversal effects of piperine and （R）-（＋）-citronellal in multidrug resistant MCF-7/DOX cells. The results of cytotoxicity studies indicated that piperine and （R）-（＋）-citronellal both could abate the resistance of MCF-7/DOX after 72-h incubation. After 72-h incubation, piperine could dose-dependently down-regulate the MDR1 expression at the mRNA level, while （R）-（＋）-citronellal had no effect on the MDR1 expression. Therefore, piperine and （R）-（＋）-citronellal both could reverse MDR in MCF-7/DOX cells, and the reversal effect ofpiperine was related to dose-dependent down-regulation of the MDR1 expression at the mRNA level.展开更多
Overexpression of P-glycoprotein(P-gp),encoded by the MDR1 gene,in tumor cells curtails the efficacy of chemotherapy,leading to multidrug resistance(MDR),which can be reversed by the P-gp inhibitor.Capsaicin,the princ...Overexpression of P-glycoprotein(P-gp),encoded by the MDR1 gene,in tumor cells curtails the efficacy of chemotherapy,leading to multidrug resistance(MDR),which can be reversed by the P-gp inhibitor.Capsaicin,the principal pungent component of hot chili,is a reported P-gp inhibitor with anti-cancer properties.In the present study,we aimed to evaluate the MDR reversal effect of capsaicin.The MCF-7/DOX cells were treated with capsaicin for a short term(3 h)or long term(72 h).The cytotoxicity studies were completed by using the SRB method.RT-PCR method was utilized to evaluate the effect of capsaicin on the expression of MDR1 at the m RNA level.The accumulation and subcellular distribution studies were implemented to further investigate the reversal effect of capsaicin.The effect of capsaicin on the ATP production of mitochondria was also evaluated.The results of the cytotoxicity study indicated that capsaicin(50μM)reversed the resistance of MCF-7/DOX cells to doxorubicin(DOX)with the reversal fold of 4.68,and concentration-dependently down-regulated the expression of MDR1 at the m RNA level after long-term(72 h)incubation.After short-term(3 h)incubation,capsaicin reversibly and concentration-dependently increased the accumulation of DOX into MCF-7/DOX cells and induced a different subcellular distribution of DOX compared with verapamil as a positive control.The ATP production of mitochondria was also concentration-dependently inhibited by capsaicin.In conclusion,capsaicin was capable of reversing the resistance of MCF-7/DOX cells to DOX,making it a promising lead compound for MDR reversal.展开更多
基金Supported by DP2M DIKTI(Directorate of higher Education)Ministry of Education Indonesia trough HKI research grant 2011
文摘Objective:To evaluate of hesperidin to overcome resistance of doxorubicin in MCF-7 resistant doxorubicin cells(MCF-7/Dox)in cytotoxicity apoptosis and P-glycoprotein(Pgp)expression in combination with doxorubicin.Methods:The cytotoxic properties.50%inhibition concentration(IC_(50))and its combination with doxorubicin in MCF-7 cell lines resistant to doxorubicin(MCF-7/Dox)cells were determined using MTT assay.Apoptosis induction was examined by double staining assay using ethidium bromide-acridine orange.Immunocytochemistry assay was performed to determine the level and localization of Pgp.Results:Single treatment of hesperidin showed cytotoxic activity on MCF-7/Dox cells with IC_(50)value of 11μmol/L.Thus,combination treatment from hesperidin and doxorubicin showed addictive and antagonist effect(CI>1.0).Hesperidin did not increase the apoptotic induction,but decreased the Pgp expressions level when combined with doxorubicin in low concentration.Conclusions:Hesperidin has cytotoxic effect on MCF-7/Dox cells with IC_(50)of 11μmol/L.Hesperidin did not increased the apoptotic induction combined with doxorubicin.Cochemotherapy application of doxorubicin and hesperidin on MCF-7/Dox cells showed synergism effect through inhibition of Pgp expression.
文摘Multidrug resistance （MDR） in tumor cells can reduce the efficacy of chemotherapy. Overexpression of transporters is an important mechanism for MDR. P-glycoprotein （P-gp） is an ATP-binding cassette transporter frequently expressed in multidrug resistant tumor cells, inducing MDR. To reverse P-gp dependent MDR, anticancer drugs can be administered with P-gp inhibitors. Piperine and （R）-（＋）-citronellal both are P-gp inhibitors from dietary sources. In the present study, we aimed to evaluate the MDR reversal effects of piperine and （R）-（＋）-citronellal in multidrug resistant MCF-7/DOX cells. The results of cytotoxicity studies indicated that piperine and （R）-（＋）-citronellal both could abate the resistance of MCF-7/DOX after 72-h incubation. After 72-h incubation, piperine could dose-dependently down-regulate the MDR1 expression at the mRNA level, while （R）-（＋）-citronellal had no effect on the MDR1 expression. Therefore, piperine and （R）-（＋）-citronellal both could reverse MDR in MCF-7/DOX cells, and the reversal effect ofpiperine was related to dose-dependent down-regulation of the MDR1 expression at the mRNA level.
文摘Overexpression of P-glycoprotein(P-gp),encoded by the MDR1 gene,in tumor cells curtails the efficacy of chemotherapy,leading to multidrug resistance(MDR),which can be reversed by the P-gp inhibitor.Capsaicin,the principal pungent component of hot chili,is a reported P-gp inhibitor with anti-cancer properties.In the present study,we aimed to evaluate the MDR reversal effect of capsaicin.The MCF-7/DOX cells were treated with capsaicin for a short term(3 h)or long term(72 h).The cytotoxicity studies were completed by using the SRB method.RT-PCR method was utilized to evaluate the effect of capsaicin on the expression of MDR1 at the m RNA level.The accumulation and subcellular distribution studies were implemented to further investigate the reversal effect of capsaicin.The effect of capsaicin on the ATP production of mitochondria was also evaluated.The results of the cytotoxicity study indicated that capsaicin(50μM)reversed the resistance of MCF-7/DOX cells to doxorubicin(DOX)with the reversal fold of 4.68,and concentration-dependently down-regulated the expression of MDR1 at the m RNA level after long-term(72 h)incubation.After short-term(3 h)incubation,capsaicin reversibly and concentration-dependently increased the accumulation of DOX into MCF-7/DOX cells and induced a different subcellular distribution of DOX compared with verapamil as a positive control.The ATP production of mitochondria was also concentration-dependently inhibited by capsaicin.In conclusion,capsaicin was capable of reversing the resistance of MCF-7/DOX cells to DOX,making it a promising lead compound for MDR reversal.
