Drug Transporter-independent Liver Cancer Cell Killing by a Marine Steroid Methyl Spongoate via Apoptosis Induction

doi:10.1074/jbc.M111.232728

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	Drug Transporter-independent Liver Cancer Cell Killing by a Marine Steroid Methyl Spongoate via Apoptosis Induction
	Jiang, Yi; Miao, Ze-Hong; Xu, Lei; Yu, Bing; Gong, Jing-Xu; Tong, Lin-Jiang; Chen, Yi; Zhou, Zhao-Li; Liu, Hong-Chun; Wang, Yi
刊名	JOURNAL OF BIOLOGICAL CHEMISTRY
	2011-07-29
卷号	286 期号:30 页码:26461-26469
ISSN号	0021-9258
DOI	10.1074/jbc.M111.232728
文献子类	Article
英文摘要	Hepatocellular carcinoma (HCC) is inherently resistant to the majority of clinical anticancer drugs. To obtain drugs that can circumvent or evade such inherent drug resistance of HCC, we investigated the effect of the marinely derived steroid methyl spongoate (MESP) on HCC cells. MESP displayed potent cell killing against a panel of six HCC cell lines, independent of their expression of drug transporters. MESP did not change the function of the drug transporters, and its cell killing was not impaired in multidrug-resistant cancer cells overexpressing the transporters. The cell killing of MESP was irrelevant to estrogen or androgen signaling and was not associated with cell cycle progression, inhibition of microtubules, and topoisomerases. In contrast, MESP potently induced apoptosis via activation of a proapoptotic caspase cascade and relief of the suppression of antiapoptotic signal transducers and activators of transcription 3 (STAT3) signaling. MESP inhibited the phosphorylation of STAT3, a critical survival signaling factor that reduced the expression of the antiapoptotic protein x-linked inhibitor of apoptosis protein but enhanced the expression of the proapoptotic protein Bax, thus promoting caspase-dependent apoptosis. These data reveal that MESP may well serve as an important candidate drug lead for HCC therapy.
资助项目	National Natural Science Foundation of China[81025020] ; National Natural Science Foundation of China[81021062] ; National Natural Science Foundation of China[21072204] ; National Natural Science Foundation of China[30730108] ; National Basic Research Program of China[2010CB934000] ; Chinese Academy of Sciences[KSCX1-YW-22] ; Chinese Academy of Sciences[SIMM0907KF-09] ; Science and Technology Commission of Shanghai Municipality[09540704100]
WOS关键词	HEPATOCELLULAR-CARCINOMA ; TOPOISOMERASE-II ; DOWN-REGULATION ; MULTIDRUG-RESISTANCE ; MEDIATED APOPTOSIS ; PROSTATE-CANCER ; BREAST-CANCER ; TUMOR-CELLS ; SALVICINE ; STAT3
WOS研究方向	Biochemistry & Molecular Biology
语种	英语
出版者	AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
WOS记录号	WOS:000293078200024
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/278468]
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药物靶标结构与功能中心
通讯作者	Miao, Ze-Hong
作者单位	Chinese Acad Sci, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Jiang, Yi,Miao, Ze-Hong,Xu, Lei,et al. Drug Transporter-independent Liver Cancer Cell Killing by a Marine Steroid Methyl Spongoate via Apoptosis Induction[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2011,286(30):26461-26469.
APA	Jiang, Yi.,Miao, Ze-Hong.,Xu, Lei.,Yu, Bing.,Gong, Jing-Xu.,...&Ding, Jian.(2011).Drug Transporter-independent Liver Cancer Cell Killing by a Marine Steroid Methyl Spongoate via Apoptosis Induction.JOURNAL OF BIOLOGICAL CHEMISTRY,286(30),26461-26469.
MLA	Jiang, Yi,et al."Drug Transporter-independent Liver Cancer Cell Killing by a Marine Steroid Methyl Spongoate via Apoptosis Induction".JOURNAL OF BIOLOGICAL CHEMISTRY 286.30(2011):26461-26469.