Xanthohumol suppresses oestrogen-signalling in breast cancer through the inhibition of BIG3-PHB2 interactions

Tetsuro Yoshimaru, Masato Komatsu, Etsu Tashiro, Masaya Imoto, Hiroyuki Osada, Yasuo Miyoshi, Junko Honda, Mitsunori Sasa, Toyomasa Katagiri

研究成果: Article査読

47 被引用数 (Scopus)

抄録

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.

本文言語English
論文番号7355
ジャーナルScientific reports
4
DOI
出版ステータスPublished - 2014 12 8

ASJC Scopus subject areas

  • 一般

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