Yoshimaru Tetsuro, Komatsu Masato, Tashiro Etsu, Imoto Masaya, Osada Hiroyuki, Miyoshi Yasuo, Honda Junko, Sasa Mitsunori, Katagiri Toyomasa
Division of Genome Medicine, Institute for Genome Research, The University of Tokushima, Tokushima, Japan.
Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, Kanagawa, Japan.
Sci Rep. 2014 Dec 8;4:7355. doi: 10.1038/srep07355.
Xanthohumol (XN) is a natural anticancer compound that inhibits the proliferation of oestrogen receptor-α (ERα)-positive breast cancer cells. However, the precise mechanism of the antitumour effects of XN on oestrogen (E2)-dependent cell growth, and especially its direct target molecule(s), remain(s) largely unknown. Here, we focus on whether XN directly binds to the tumour suppressor protein prohibitin 2 (PHB2), forming a novel natural antitumour compound targeting the BIG3-PHB2 complex and acting as a pivotal modulator of E2/ERα signalling in breast cancer cells. XN treatment effectively prevented the BIG3-PHB2 interaction, thereby releasing PHB2 to directly bind to both nuclear- and cytoplasmic ERα. This event led to the complete suppression of the E2-signalling pathways and ERα-positive breast cancer cell growth both in vitro and in vivo, but did not suppress the growth of normal mammary epithelial cells. Our findings suggest that XN may be a promising natural compound to suppress the growth of luminal-type breast cancer.
黄腐酚（XN）是一种天然抗癌化合物，可抑制雌激素受体α（ERα）阳性乳腺癌细胞的增殖。然而，XN对雌激素（E2）依赖性细胞生长的抗肿瘤作用的确切机制，尤其是其直接靶分子，在很大程度上仍不清楚。在此，我们关注XN是否直接与肿瘤抑制蛋白抑制素2（PHB2）结合，形成一种靶向BIG3-PHB2复合物的新型天然抗肿瘤化合物，并作为乳腺癌细胞中E2/ERα信号传导的关键调节因子。XN处理有效地阻止了BIG3-PHB2相互作用，从而释放PHB2以直接结合核内和胞质中的ERα。这一事件导致E2信号通路和ERα阳性乳腺癌细胞在体外和体内的生长完全受到抑制，但不抑制正常乳腺上皮细胞的生长。我们的研究结果表明，XN可能是一种有前景的天然化合物，可抑制管腔型乳腺癌的生长。
