Liquiritigenin Enhances the Inhibitory Effects of the Cholesterol Biosynthesis Inhibitor RO 48-8071 on Cell Viability in Ovarian-Cancer Cells in Vitro

Author(s): Yayun Liang and Salman M Hyder

Almost 25,000 new cases of epithelial ovarian cancer (EOC) are reported each year in the United States. Cancers of the ovary have poor prognosis due to drug resistance and metastasis, and have the highest mortality rate of all the known gynecological malignancies. Despite concerted efforts to develop new strategies for preventing and treating ovarian cancer, novel and more effective non-toxic therapies for ovarian cancer are urgently needed. Recent observations show that RO 48-8071 ([4’-[6-(Allylmethylamino)hexyloxy]-4-bromo-2’-fluorobenzophenone fumarate] [RO], a small-molecule inhibitor of the key cholesterol biosynthesis enzyme 2, 3-oxidosqualene cyclase, inhibits breast and prostate cancer cells. RO also induces the tumor-suppressor protein estrogen receptor (ER) β in both breast- and prostate-cancer cells, and also inhibits growth of ovarian-cancer cells both in vitro and in vivo. Extending upon these earlier studies, here we found that RO also induces ERβ expression in OVCAR-3 ovarian-cancer cells. Further, we demonstrated that treatment of two ovarian-cancer cell lines (OVCAR-3 and SK-OV-3) with liquiritigenin (LQ), a naturally occurring compound that is an ERβ agonist, reduced cell viability in vitro. When we treated OVCAR-3 and SK-OV-3 cells with RO, LQ, or RO + LQ, we observed that RO + LQ combination treatment synergistically reduced cell viability. Further in vivo studies examining the effects of RO + LQ combination treatment on EOC are warranted, as a means of exploring a potential new therapeutic approach to combat ovarian cancers with minimal toxicity.