The Chinese Herb Isolate Isorhapontigenin Induces Apoptosis in Human Cancer Cells by Down-regulating Overexpression of Antiapoptotic Protein XIAP
The Chinese Herb Isolate Isorhapontigenin Induces Apoptosis in Human Cancer Cells by Down-regulating Overexpression of Antiapoptotic Protein XIAP
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DOI：
10.1074/jbc.m112.389494
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发表时间：
2012-10-12
影响因子：
4.8
通讯作者：
Huang, Chuanshu
中科院分区：
文献类型：
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作者：
Fang, Yong;Yu, Yonghui;Huang, Chuanshu
虽然中药买麻藤作为抗癌药物已有数百年的历史，但其抗癌活性成分及其分子机制尚未得到研究。本研究以异甘草素（isorhapontigenin，ISO）为主要研究对象，对ISO的抗肿瘤活性及其作用机制进行了初步探讨。我们发现，ISO对人膀胱癌细胞的生长表现出显着的抑制作用，伴随着显着的凋亡诱导以及下调的X-连锁的凋亡抑制蛋白（XIAP）。进一步的研究表明，ISO下调XIAP蛋白表达仅在内源性XIAP中观察到，但在相同细胞中组成性外源表达的XIAP中未观察到，排除了ISO在蛋白降解水平上调节XIAP表达的可能性。我们还发现，ISO下调XIAP基因转录通过抑制Sp1的反式激活。ISO对外源性HA标记的XIAP转染的细胞的凋亡和集落形成没有显著影响。总的来说，目前的研究，第一次尽我们所知，确定ISO作为一个主要的活性化合物的抗癌活性的G。通过特异性靶向SP1通路下调XIAP表达和诱导细胞凋亡，为XIAP过表达的癌症患者的治疗提供了新的思路。
Although the Chinese herb Gnetum cleistostachyum has been used as a remedy for cancers for hundred years, the active compounds and molecular mechanisms underlying its anti-cancer activity have not been explored. Recently a new derivative of stilbene compound, isorhapontigenin (ISO), was isolated from this Chinese herb. In the present study, we examined the potential of ISO in anti-cancer activity and the mechanisms involved in human cancer cell lines. We found that ISO exhibited significant inhibitory effects on human bladder cancer cell growth that was accompanied by marked apoptotic induction as well as down-regulation of the X-linked inhibitor of apoptosis protein (XIAP). Further studies have shown that ISO down-regulation of XIAP protein expression was only observed in endogenous XIAP, but not in constitutionally exogenously expressed XIAP in the same cells, excluding the possibility of ISO regulating XIAP expression at the level of protein degradation. We also identified that ISO down-regulated XIAP gene transcription via inhibition of Sp1 transactivation. There was no significant effect of ISO on apoptosis and colony formation of cells transfected with exogenous HA-tagged XIAP. Collectively, current studies, for the first time to the best of our knowledge, identify ISO as a major active compound for the anti-cancer activity of G. cleistostachyum by down-regulation of XIAP expression and induction of apoptosis through specific targeting of a SP1 pathway, and cast new light on the treatment of the cancer patients with XIAP overexpression.