Hypericum sampsonii induces apoptosis and nuclear export of retinoid X receptor-alpha

Abstract

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 (RXRα) represents a potential approach for inducing cancer cell apoptosis. In this study, we screened a herbal library for inducing translocation of RXRα 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 RXRα subcellular localization in various cancer cells. Treatment of NIH-H460 human lung cancer cells with H.sampsonii extract resulted in relocalization of RXRα from the nucleus to the cytoplasm. Cytoplasmic RXRα 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 RXRα, as it failed to inhibit the growth of CV-1 cells lacking detectable RXRα, whereas transfection of RXRα into CV-1 cells restored its apoptotic response to H.sampsonii. Furthermore, the apoptotic effect of H.sampsonii was significantly enhanced when RXRα 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 RXRα. © 2006 Oxford University Press.