Dihydroartemisinin accelerates c-MYC oncoprotein degradation and induces apoptosis in c-MYC-overexpressing tumor cells
文献类型：期刊论文
| 作者 | Lu, Jin-Jian2; Meng, Ling-Hua2 ; Shankavaram, Uma T.1; Zhua, Cai-Hua2; Tong, Lin-Jiang2; Chen, Guang2; Lin, Li-Ping2; Weinstein, John N.3; Ding, Jian2
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| 刊名 | BIOCHEMICAL PHARMACOLOGY
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| 出版日期 | 2010-07-01 |
| 卷号 | 80期号:1页码:22-30 |
| 关键词 | Dihydroartemisinin NCI-60 c-MYC Apoptosis GSK 3 beta |
| ISSN号 | 0006-2952 |
| DOI | 10.1016/j.bcp.2010.02.016 |
| 文献子类 | Article |
| 英文摘要 | Artemisinin and its derivatives (ARTS) are effective antimalarial drugs and also possess profound anticancer activity. However, the mechanism accounted for its distinctive activity in tumor cells remains unelucidated. We computed Pair wise Pearson correlation coefficients to identify genes that show significant correlation with ARTs activity in NCI-55 cell lines using data obtained from studies with HG-U133A Affymetrix chip. We found c-myc is one of the genes that showed the highest positive correlation coefficients among the probe sets analyzed (r = 0.585, P < 0.001). Dihydroartemisinin (DHA), the main active metabolite of ARTs, induced significant apoptosis in HL-60 and HCT116 cells that express high levels of c-MYC. Stable knockdown of c-myc abrogated DHA-induced apoptosis in HCT116 cells. Conversely, forced expression of c-myc in NIH3T3 cells sensitized these cells to DHA-induced apoptosis. Interestingly. DHA irreversibly down-regulated the protein level of c-MYC in DHA-sensitive HCT116 cells, which is consistent to persistent G1 phase arrest induced by DHA. Further studies demonstrated that DHA accelerated the degradation of c-MYC protein and this process was blocked by pretreatment with the proteasome inhibitor MG-132 or GSK 3 beta inhibitor LiCl in HCT116 cells. Taken together, ARTs might be useful in the treatment of c-MYC-overexpressing tumors. We also suggest that c-MYC may potentially be a biomarker candidate for prediction of the antitumor efficacies of ARTS. (C) 2010 Elsevier Inc. All rights reserved. |
| WOS关键词 | IN-VITRO ; ANTIMALARIAL ARTESUNATE ; COLORECTAL-CARCINOMA ; HISTONE GAMMA-H2AX ; PROTEIN STABILITY ; CANCER-CELLS ; GROWTH ; ARTEMISININ ; EXPRESSION ; ACTIVATION |
| 资助项目 | National Natural Science of China[30701026] ; National Natural Science of China[30721005] ; National Science & Technology Major Project "Key New Drug Creation and Manufacturing Program"[2009ZX09301-001] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000277497600003 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278846]  |
| 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 | Meng, Ling-Hua |
| 作者单位 | 1.NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China; 3.Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA |
| 推荐引用方式 GB/T 7714 | Lu, Jin-Jian,Meng, Ling-Hua,Shankavaram, Uma T.,et al. Dihydroartemisinin accelerates c-MYC oncoprotein degradation and induces apoptosis in c-MYC-overexpressing tumor cells[J]. BIOCHEMICAL PHARMACOLOGY,2010,80(1):22-30. |
| APA | Lu, Jin-Jian.,Meng, Ling-Hua.,Shankavaram, Uma T..,Zhua, Cai-Hua.,Tong, Lin-Jiang.,...&Ding, Jian.(2010).Dihydroartemisinin accelerates c-MYC oncoprotein degradation and induces apoptosis in c-MYC-overexpressing tumor cells.BIOCHEMICAL PHARMACOLOGY,80(1),22-30. |
| MLA | Lu, Jin-Jian,et al."Dihydroartemisinin accelerates c-MYC oncoprotein degradation and induces apoptosis in c-MYC-overexpressing tumor cells".BIOCHEMICAL PHARMACOLOGY 80.1(2010):22-30. |
入库方式： OAI收割
来源：上海药物研究所
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