ω-3 free fatty acids and all-trans retinoic acid synergistically induce growth inhibition of three subtypes of breast cancer cell lines

All-trans retinoic acid (ATRA), one of vitamin A derivatives, shows greater growth inhibition of breast cancer cell for ER-positive than ER-negative cells, while triple negative breast cancer cell such as MDA-MB-231 cell is poorly responsive to ATRA treatment. In this study, we found that combination of ω-3 free fatty acids (ω-3 FFAs) and ATRA exhibited synergistic inhibition of cell growth in three subtypes (ER(+) MCF7, HER2(+) SK-BR-3, Triple negative HCC1806 and MDA-MB-231 cells) of human breast cancer cell lines. The combined treatment of ω-3 FFAs and ATRA resulted in cell cycle arrest. ω-3 FFAs combined with ATRA synergistically provoked cell apoptosis via the caspase signals but not p53. These findings suggest that combined chemotherapy of ω-3 FFAs with ATRA is beneficial for improvement of ATRA sensitivity in breast cancer cells.