Open AccessSilybin suppresses ovarian cancer cell proliferation by inhibiting isocitrate dehydrogenase 1 activity
Author(s) -
Wei Zibo,
Ye Shuangyan,
Feng Haipeng,
Zeng Chong,
Dong Xinhuai,
Zeng Xiaokang,
Zeng Liming,
Lin Xu,
Liu Qiuzhen,
Yao Jie
Publication year - 2022
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.15470
Subject(s) - isocitrate dehydrogenase , ovarian cancer , idh1 , cancer research , glutamine , cell growth , cancer cell , biology , cancer , cell cycle , chemistry , cell , biochemistry , enzyme , amino acid , gene , mutation , genetics
Metabolic reprogramming is a sign of malignant tumors, and targeting the metabolism of tumor cells has become a promising therapeutic approach. Here, we report that Silybin (a nontoxic flavonoid commonly used for liver protection) exhibits prominent anti‐tumor effects on human ovarian cancer cells. Treatment of an ovarian cancer cell line with Silybin interfered with glutamine metabolism and the tricarboxylic acid cycle. We applied the drug affinity responsive target stability approach to show that Silybin binds to isocitrate dehydrogenase 1 (IDH1). This combination leads to reduced phosphorylation of IDH1 and inhibits enzyme activity. IDH1 dysfunction significantly increases the ratio of NADP/NADPH in the cell, causing an increase in reactive oxygen species generation. Immunohistochemistry demonstrated that IDH1 was increased in ovarian cancer samples compared with normal para‐tumoral tissues. Xenograft murine experiments indicated that Silybin administered orally suppressed the growth of the tumor formed by ovarian cancer cells. In combination, our data strongly suggest that Silybin targets IDH1 in ovarian cancer cells and may be a novel treatment candidate.