Vitamin D and docosahexaenoic acid inhibit proliferation of the ovarian cancer cell line OVCAR4

Background: Ovarian cancer is one of the deadliest cancers in women. Improved preventative, diagnostic, and therapeutic strategies are needed. Certain dietary patterns and nutrients such as vitamin D and omega-3 fatty acids are associated with reduced cancer risk, but their effects on ovarian cancer remain to be fully elucidated, and their combined effects have not been explored. Aim: To determine the individual and combined effects of the active vitamin D metabolite, calcitriol, and the omega-3 fatty acid, docosahexaenoic acid, on cell growth, and the abundance of the vitamin D receptor (VDR), proteins that modulate cell cycle progression, and apoptotic markers. Methods: OVCAR4 cells, a model of ovarian cancer, were treated with calcitriol, and docosahexaenoic acid, either alone or in combination. Effects on cell growth were determined by the sulforhodamine B assay. Changes in VDR, the cell cycle promotor c-Myc, the cell cycle inhibitor p27 and cleaved PARP, were determined by Western blotting. Results: While OVCAR4 cell growth was inhibited by individual treatment with either calcitriol or docosahexaenoic acid, the combined treatment revealed enhanced growth inhibition as compared to either treatment alone. Furthermore, long-term treatment (12 days) yielded stronger growth inhibition at lower concentrations as compared to short-term treatments (3 days). Accompanying this growth inhibition was a decrease in c-Myc, and an increase in p27. Conclusions: The observed reduction in cell growth mediated by calcitriol and docosahexaenoic acid highlights the need for further research utilizing these nutrients, alone and especially in combination, to support ovarian cancer prevention and treatment.