Phytoestrogen Signal Pathways and Estrogen Signaling in Ovarian Cancer: A Narrative Review

Ovarian cancer (OC) is the second most common gynecological cancer and the leading cause of death from gynecological malignancies. Ovarian cancer mortality rate ranks fifth among cancer-related deaths in Western societies. Hence, novel preventive and therapeutic ways are still in great demand to reduce the incidence and mortality rate of ovarian cancer. Phytoestrogens, referred to as dietary estrogens, provide benefits to all mammals, including humans. Research indicates that phytoestrogens may be possible hormonal treatment options for ovarian cancer patients. They are non-steroidal plant compounds that undergo metabolism to produce compounds structurally and functionally related to ovarian and placental estrogens. Some studies suggest that estrogen receptors (ER-α and ER-β) and G protein-coupled estrogen receptor (GPER) are potential targets for ovarian cancer prevention and treatment. Current studies indicate multiple signal pathways of phytoestrogens in the management of ovarian cancer. Even so, literature suggests that the signaling mechanisms in ovarian cancer and the signaling mechanisms of phytoestrogens are still not exactly understood. With this, phytoestrogens may act on multiple signaling pathways such as ER (endoplasmic reticulum)-dependent signaling, GnRH receptor, FSH or LH receptors and hormones, and GFR, which help to regulate the expression of AKT, RAS, RAF, Caspase-3, NF-kB, and Bcl-2. In summary, this narrative review discusses the possible targets of phytoestrogens in ovarian cancer and sheds a light on improving novel phytoestrogens-based dietary supplements against ovarian cancers.