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	NSAID Sulindac and Its Analog Bind RXR alpha and Inhibit RXR alpha-Dependent AKT Signaling
	Zhou, Hu ; Liu, Wen（Sanford Burnham Med Res Inst, La Jolla） ; Su, Ying（Sanford Burnham Med Res Inst, La Jolla） ; Wei, Zhen ; Liu, Jie ; Kolluri, Siva Kumar（Oregon State Univ, Dept Environm & Mol Toxicol） ; Wu, Hua ; Cao, Yu（Sanford Burnham Med Res Inst, La Jolla） ; Chen, Jiebo（Sanford Burnham Med Res Inst, La Jolla） ; Wu, Yin（Sanford Burnham Med Res Inst, La Jolla） ; Yan, Tingdong ; Cao, Xihua（Sanford Burnham Med Res Inst, La Jolla） ; Gao, Weiwei ; Molotkov, Andrei（Sanford Burnham Med Res Inst, La Jolla） ; Jiang, Fuquan ; Li, Wen-Gang（First Hosp Xiamen） ; Lin, Bingzhen（Sanford Burnham Med Res Inst, La Jolla） ; Zhang, Hai-Ping（First Hosp Xiamen） ; Yu, Jinghua（Sanford Burnham Med Res Inst, La Jolla） ; Luo, Shi-Peng ; Zeng, Jin-Zhang ; Duester, Gregg（Sanford Burnham Med Res Inst, La Jolla） ; Huang, Pei-Qiang ; Huang PQ(黄培强) ; Zhang, Xiao-Kun
	2010
英文摘要	Nonsteroidal anti-inflammatory drugs (NSAIDs) exert their anticancer effects through cyclooxygenase-2 (COX-2)-dependent and independent mechanisms. Here, we report that Sulindac, an NSAID, induces apoptosis by binding to retinoid X receptor-alpha (RXR alpha). We identified an N-terminally truncated RXR alpha (tRXR alpha) in several cancer cell lines and primary tumors, which interacted with the p85 alpha subunit of phosphatidylinositol-3-OH kinase (PI3K). Tumor necrosis factor-alpha (TNF alpha) promoted tRXR alpha. interaction with the p85 alpha, activating PI3K/AKT signaling. When combined with TNF alpha, Sulindac inhibited TNF alpha-induced tRXR alpha/p85 alpha interaction, leading to activation of the death receptor-mediated apoptotic pathway. We designed and synthesized a Sulindac analog K-80003, which has increased affinity to RXR alpha but lacks COX inhibitory activity. K-80003 displayed enhanced efficacy in inhibiting tRXR alpha-dependent AKT activation and tRXR alpha tumor growth in animals.; National Institutes of Health [CA109345, CA140980, GM089927, GM062848]; Susan G. Komen Breast Cancer Foundation ; California Breast Cancer Research Program ; U.S. Army Medical Research and Material Command ; California Tobacco-Related Diseases Research Program ; Xiamen University ; 863 Program [2007aa09z404]; National Science Foundation [30971445, 30931160431]
语种	英语
出版者	CELL PRESS
内容类型	期刊论文
源URL	[http://dx.doi.org/doi:10.1016/j.ccr.2010.04.023]
专题	化学化工－已发表论文
推荐引用方式 GB/T 7714	Zhou, Hu,Liu, Wen,Su, Ying,et al. NSAID Sulindac and Its Analog Bind RXR alpha and Inhibit RXR alpha-Dependent AKT Signaling[J],2010.
APA	Zhou, Hu.,Liu, Wen.,Su, Ying.,Wei, Zhen.,Liu, Jie.,...&Zhang, Xiao-Kun.(2010).NSAID Sulindac and Its Analog Bind RXR alpha and Inhibit RXR alpha-Dependent AKT Signaling..
MLA	Zhou, Hu,et al."NSAID Sulindac and Its Analog Bind RXR alpha and Inhibit RXR alpha-Dependent AKT Signaling".(2010).

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