Soy isoflavone metabolite equol inhibits cancer cell proliferation in a PAP associated domain containing 5-dependent and an estrogen receptor-independent manner

Shuya Yamashita, Ichian Lin, Chihiro Oka, Motofumi Kumazoe, Satomi Komatsu, Motoki Murata, Shoko Kamachi, Hirofumi Tachibana

研究成果: ジャーナルへの寄稿学術誌査読

11 被引用数 (Scopus)

抄録

Isoflavone is a species of polyphenol found mainly in soy and soy products. Many studies have demonstrated its estrogen receptor (ER)-dependent action. Equol is an intestinal metabolite of a major soy isoflavone daidzein. We aimed to elucidate the mechanism for ER-independent actions of equol. Equol has been shown to inhibit proliferation of HeLa human cervical cancer cells and mouse melanoma B16 cells in an ER-independent manner. Using functional genetic screening, PAP associated domain containing 5 (PAPD5), which is a non-canonical poly(A) polymerase, was identified as an essential molecule in the ER-independent action. While peroral administration of equol inhibited tumor growth of control B16 cells subcutaneously inoculated in mice, it had little effect on the growth of PAPD5-ablated B16 cells. Intriguingly, equol progressed tumor growth of the PAPD5-ablated human breast cancer MCF-7 cells, which have high ERα expression. Equol has been found to induce polyadenylation of snoRNAs in a PAPD5-depdendent manner. Furthermore, peroral equol administration increased microRNA miR-320a expression in tumors. Together, these results suggest that equol may have a dual effect on ER-positive cancer cells, acting with, antiproliferative activity through PAPD5 and exhibiting proliferative activity via ERα and the former could be associated with miR-320a.

本文言語英語
論文番号108910
ジャーナルJournal of Nutritional Biochemistry
100
DOI
出版ステータス出版済み - 2月 2022

!!!All Science Journal Classification (ASJC) codes

  • 内分泌学、糖尿病および代謝内科学
  • 生化学
  • 分子生物学
  • 栄養および糖尿病
  • 臨床生化学

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