Carcinogenesis Advance Access published online on April 18, 2006
Carcinogenesis, doi:10.1093/carcin/bgl046
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1 Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
* To whom correspondence should be addressed. Natural products derived from plants provide a rich source for development of new anti-cancer drugs. Recent studies suggest that modulation of subcellular localization of retinoid X receptor-alpha (RXR
Received October 26, 2005
Revised March 26, 2006
Accepted March 27, 2006
CANCER BIOLOGY
Hypericum sampsonii induces apoptosis and nuclear export of retinoid X receptor-alpha
Jin-zhang Zeng 1 * 5,
De-fu Sun 1 5,
Li Wang 1,
Xihua Cao 2,
Jian-bin Qi 3,
Ting Yang 1,
Chang-qi Hu 3,
Wen Liu 2,
and
Xiao-kun Zhang 4
2 Cancer Center, Burnham Institute for Medical Research, La Jolla, CA, USA
3 School of Pharmacy, Medical Center of Fudan University, Shanghai, China
4 Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China; Cancer Center, Burnham Institute for Medical Research, La Jolla, CA, USA
Jin-zhang Zeng, E-mail: jzzeng{at}sibs.ac.cn
Abstract 
) represents a potential approach for inducing cancer cell apoptosis. In this study, we screened a herbal library for inducing translocation of RXR from the nucleus to the cytoplasm. Our results revealed that extract of Hypericum sampsonii (H. sampsonii), a member of the genus Hypericum, had remarkable effect on RXR subcellular localization in various cancer cells. Treatment of NIH-H460 human lung cancer cells with H. sampsonii extract resulted in relocalization of RXR from the nucleus to the cytoplasm. Cytoplasmic RXR 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 RXR, as it failed to inhibit the growth of CV-1 cells lacking detectable RXR, whereas transfection of RXR into CV-1 cells restored its apoptotic response to H. sampsonii. Furthermore, the apoptotic effect of H. sampsonii was significantly enhanced when RXR 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 RXR.; nuclear export; apoptosis; cancer; Hypericum sampsonii; herbal medicine.
5Equal contribution to this work
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