Reactive oxygen species contribute to cell killing and P-glycoprotein downregulation by salvicine in multidrug resistant K562/A02 cells
文献类型：期刊论文
| 作者 | Cai, Yujun; Lu, Jinjian; Miao, Zehong; Lin, Liping; Ding, Jian
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| 刊名 | CANCER BIOLOGY & THERAPY
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| 出版日期 | 2007-11 |
| 卷号 | 6期号:11页码:1794-1799 |
| 关键词 | salvicine reactive oxygen species multidrug-resistant P-glycoprocein N-acetyl-cysteine vitamin C DNA double strand breaks |
| ISSN号 | 1538-4047 |
| DOI | 10.4161/cbt.6.11.4860 |
| 文献子类 | Article |
| 英文摘要 | Salvicine, a novel diterpenoid quinone compound, displays potent antitumor activities in vitro and in vivo, which is under Phase II clinical trials for cancer therapy. Our previous studies have shown that salvicine effectively kills multidrug-resistant (MDR) cells and downregulates mdr-1 and P-glycoprotein (P-gp) levels by activation of transcription factor c-Jun in MDR K562/A02 cells. Recent studies have further demonstrated that salvicine-formed reactive oxygen species (ROS) contribute to its induction of cytotoxicity, DNA double strand breaks and apoptosis. In this study, we showed that salvicine induced equal ROS generation and glutathione depletion in both sensitive K562 and MDR K562/A02 cells. Pre-incubation with thiol antioxidants glutathione or N-acetyl-cysteine (NAC, precursor of intracellular glutathione) almost abolished the cytotoxicity of salvicine, which also could be attenuated by the H2O2-specific scavenger catalase. Moreover, NAC abrogated salvicine-induced DNA double strand breaks and apoptosis. Notably, both H2O2 and vitamin C potentiated the cytotoxicity and apoptotic induction of salvicine in parental K562 and MDR K562/A02 cells, and catolase could remove such potentiation. Furthermore, pretreatment of K562/A02 cells with NAC eliminated P-gp, downregulation, JNK phosphorylation and c-Jun activation induced by salvicine. Our data collectively indicate that salvicine-generated ROS contribute to both cell killing and P-gp downregulation in MDR K562/A02 cells, thus extending our prior related studies. This study also opens the possibility of the combination therapy of salvicine and vitamin C in the future. |
| WOS关键词 | DNA TOPOISOMERASE-II ; DOUBLE-STRAND BREAKS ; VITAMIN-C ; ANTITUMOR-ACTIVITY ; HYDROGEN-PEROXIDE ; LEUKEMIA-CELLS ; APOPTOSIS ; CANCER ; CYTOTOXICITY ; ACTIVATION |
| WOS研究方向 | Oncology |
| 语种 | 英语 |
| WOS记录号 | WOS:000253944600030 |
| 出版者 | LANDES BIOSCIENCE |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/273120]  |
| 专题 | 药理学第一研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Ding, Jian |
| 作者单位 | Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Div Anti Tumor Pharmacol, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Cai, Yujun,Lu, Jinjian,Miao, Zehong,et al. Reactive oxygen species contribute to cell killing and P-glycoprotein downregulation by salvicine in multidrug resistant K562/A02 cells[J]. CANCER BIOLOGY & THERAPY,2007,6(11):1794-1799. |
| APA | Cai, Yujun,Lu, Jinjian,Miao, Zehong,Lin, Liping,&Ding, Jian.(2007).Reactive oxygen species contribute to cell killing and P-glycoprotein downregulation by salvicine in multidrug resistant K562/A02 cells.CANCER BIOLOGY & THERAPY,6(11),1794-1799. |
| MLA | Cai, Yujun,et al."Reactive oxygen species contribute to cell killing and P-glycoprotein downregulation by salvicine in multidrug resistant K562/A02 cells".CANCER BIOLOGY & THERAPY 6.11(2007):1794-1799. |
入库方式： OAI收割
来源：上海药物研究所
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