Abstract
Formononetin is an isoflavone that is extracted from red clovers or soy. It has anti-oxidant, anti-proliferative, and anti-tumor effects against cells in various diseases. Several cohort studies have indicated that phytoestrogen intake, including formononetin, could reduce the risk of various carcinogenesis. In fact, many case-control studies have indicated the potential value of flavonoids as drug supplements in the treatment of many cancer patients. However, the toxic effects and the anti-cancer mechanism of formononetin in ovarian cancer are unknown. We investigated the toxicological mechanism of formononetin in ES2 and OV90 ovarian cancer cells. Formononetin suppressed cell proliferation through sub G0/G1 phase arrest and increased apoptosis in both cell lines. Furthermore, it induced loss of mitochondrial membrane potential and generation of reactive oxygen species in ES2 and OV90 cells. The formononetin-mediated regulation of cell proliferation and apoptosis involved decreased phosphorylation of ERK1/2, P90RSK, AKT, P70S6K, and S6 proteins, and increased phosphorylation of P38 protein in ES2 and OV90 cells. Co-treatment of formononetin with pharmacological inhibitors (LY294002 or U0126) revealed additional anti-proliferative effects on the two human ovarian cancer cell types. Conclusively, the results indicate the potential value of formononetin as an anti-cancer agent in human ovarian cancer.
Original language | English |
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Pages (from-to) | 7377-7387 |
Number of pages | 11 |
Journal | Journal of cellular biochemistry |
Volume | 119 |
Issue number | 9 |
DOIs | |
Publication status | Published - 2018 Sept |
Bibliographical note
Funding Information:This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute funded by the Ministry of Health & Welfare (grant number: No. HI15C0810 awarded to G.S. and HI17C0929 awarded to W.L.).
Publisher Copyright:
© 2018 Wiley Periodicals, Inc.
Keywords
- cell death mechanism
- formononetin
- ovarian cancer
- signal transduction
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology