Mitochondria-targeting drug oligomycin blocked P-glycoprotein activity and triggered apoptosis in doxorubicin-resistant HepG2 cells
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摘要Background: Mitochondria are key regulators in apoptosis. This suggests that a mitochondrion can be a target for cancer treatment. To examine the feasibility of this approach, we investigated the effect of oligomycin on the induction of apoptosis in drug-resistant cells. As a mitochondrion-targeting agent, oligomycin inhibits mitochondrial F0F1-ATPase. Of 37,000 molecules tested against the 60 human cancer cell lines of the National Cancer Institute, oligomycin is among the top 0.1% most cell line selective agents. Methods: Changes in the doxorubicin (Dox) accumulation and mitochondrial potential (Deltapsim) in human hepatocarcinoma HepG2 and its derivative R-HepG2 with Dox resistance were determined by flow cytometry. P-glycoprotein (Pgp) expression and release of cytochrome c from mitochondria were analyzed by Western blot. Cytotoxicity was examined by DNA fragmentation and the alamar blue assay. Results: R-HepG2 cells produced Pgp, showed drug resistance and accumulated less Dox when compared to their parent. In both cell lines, oligomycin depolarized Deltapsim, released cytochrome c and elicited DNA fragmentation. Moreover, oligomycin blocked Pgp activity and accumulated more Dox in R-HepG2. Combined treatment with Dox and oligomycin elicited more cell death. Conclusion: Our results suggest that oligomycin could bypass Dox resistance and trigger apoptosis in R-HepG2 cells. Copyright (C) 2004 S. Karger AG, Basel.
著者Li YC, Fung KP, Kwok TT, Lee CY, Suen YK, Kong SK
期刊名稱Chemotherapy
出版年份2004
月份1
日期1
卷號50
期次2
出版社KARGER
頁次55 - 62
國際標準期刊號0009-3157
語言英式英語
關鍵詞apoptosis; drug resistance; mitochondria; oligomycin; P-glycoprotein
Web of Science 學科類別Oncology; ONCOLOGY; Pharmacology & Pharmacy; PHARMACOLOGY & PHARMACY

上次更新時間 2020-03-08 於 04:15