Hypericum sampsonii induces apoptosis and nuclear export of retinoid X receptor-alpha.
Hypericum sampsonii induces apoptosis and nuclear export of retinoid X receptor-alpha.
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DOI：
10.1093/carcin/bgl046
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发表时间：
2006-10
期刊：
影响因子：
4.7
通讯作者：
Jin-Zhang Zeng;De-fu Sun;Li Wang;Xihua Cao;J. Qi;Ting-song Yang;Chang-qi Hu;Wen Liu;Xiao-kun Zhang
中科院分区：
文献类型：
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作者：
Jin-Zhang Zeng;De-fu Sun;Li Wang;Xihua Cao;J. Qi;Ting-song Yang;Chang-qi Hu;Wen Liu;Xiao-kun Zhang
植物源天然产物为开发新型抗肿瘤药物提供了丰富的资源。最近的研究表明，调节维甲酸X受体α（RXR α）的亚细胞定位是诱导癌细胞凋亡的一种潜在途径。在这项研究中，我们筛选了一个草药库诱导易位RXR α从细胞核到细胞质。我们的研究结果表明，金丝桃属成员的金丝桃提取物对各种癌细胞中的RXR α亚细胞定位具有显著影响。用H. sampsonii提取物导致RXR α从细胞核重新定位到细胞质。H. sampsonii与线粒体结合，伴随细胞色素c释放和凋亡。H.丹参提取物能有效抑制多种肿瘤细胞的生长，包括NIH-H460肺癌、MGC-803胃癌和SMMC 7721肝癌细胞。H. sampsonii提取物依赖于RXR α的水平，因为它不能抑制缺乏可检测到的RXR α的CV-1细胞的生长，而将RXR α转染到CV-1细胞中恢复了其对H. sampsonii。此外，H.当RXR α在NIH-H460细胞中过表达时，sampsonii的表达显著增强。总之，我们的结果表明，H。sampsonii含有通过调节RXR α的亚细胞定位诱导癌细胞凋亡的成分。
Natural products derived from plants provide a rich source for development of new anticancer drugs. Recent studies suggest that modulation of subcellular localization of retinoid X receptor-alpha (RXRalpha) represents a potential approach for inducing cancer cell apoptosis. In this study, we screened a herbal library for inducing translocation of RXRalpha from the nucleus to the cytoplasm. Our results revealed that the extract of Hypericum sampsonii, a member of the genus Hypericum, had remarkable effect on RXRalpha subcellular localization in various cancer cells. Treatment of NIH-H460 human lung cancer cells with H. sampsonii extract resulted in relocalization of RXRalpha from the nucleus to the cytoplasm. Cytoplasmic RXRalpha induced by H. sampsonii was associated with mitochondria, accompanied with cytochrome c release and apoptosis. H. sampsonii extract effectively inhibited the growth of various cancer cell lines, including NIH-H460 lung cancer, MGC-803 stomach cancer and SMMC7721 liver cancer cells. The growth inhibitory effect of H. sampsonii extract depended on levels of RXRalpha, as it failed to inhibit the growth of CV-1 cells lacking detectable RXRalpha, whereas transfection of RXRalpha into CV-1 cells restored its apoptotic response to H. sampsonii. Furthermore, the apoptotic effect of H. sampsonii was significantly enhanced when RXRalpha was overexpressed in NIH-H460 cells. Together, our results demonstrate that H. sampsonii contains ingredient(s) that induce apoptosis of cancer cells by modulating subcellular localization of RXRalpha.