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. Issue 9 (15th May 2018)

• Record Type: Journal Article
• Authors: Park, Sunwoo; Bazer, Fuller W.; Lim, Whasun; Song, Gwonhwa
• Is Part Of: Journal of cellular biochemistry. Volume 119:Issue 9(2018)
• Page Start: 7377
• Page End: 7387
• Publication Date: 2018-05-15
• Subjects: cell death mechanism -- formononetin -- ovarian cancer -- signal transduction; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.27041
• Languages: English
• ISSNs: 0730-2312

Abstract

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. Abstract : Formononetin inhibits ovarian cancer cell proliferation by sub G0/G1 cell phase arrest through PI3K/AKT and ERK1/2 inactivation. Furthermore, formononetin promotes cell apoptosis with DNA fragmentation through MMP disruption and ROS accumulation, followed by P38 activation in ES2 and OV90 cells. Our findings support the previous cohort results concerning formononetin intake in ovarian cancer patients.