The O-methylated isoflavone, formononetin, inhibits human ovarian cancer cell proliferation by sub G0/G1 cell phase arrest through PI3K/AKT and ERK1/2 inactivation
- Authors
- Park, Sunwoo; Bazer, Fuller W.; Lim, Whasun; Song, Gwonhwa
- Issue Date
- 9월-2018
- Publisher
- WILEY
- Keywords
- cell death mechanism; formononetin; ovarian cancer; signal transduction
- Citation
- JOURNAL OF CELLULAR BIOCHEMISTRY, v.119, no.9, pp.7377 - 7387
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF CELLULAR BIOCHEMISTRY
- Volume
- 119
- Number
- 9
- Start Page
- 7377
- End Page
- 7387
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/73273
- DOI
- 10.1002/jcb.27041
- ISSN
- 0730-2312
- 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.
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Collections - Graduate School > Department of Biotechnology > 1. Journal Articles
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