Vitamin D enhances omega-3 polyunsaturated fatty acids-induced apoptosis in breast cancer cells

Breast cancer is a leading type of cancer in women and generally classified into three subtypes of ER⁺ /PR⁺ , HER2⁺ and triple negative. Both omega-3 polyunsaturated fatty acids and vitamin D₃ play positive role in the reduction of breast cancer incidence. However, whether combination of omega-3 polyunsaturated fatty acids and vitamin D₃ has stronger protective effect on breast carcinogenesis still remains unknown. In this study, we show that the combination of ω-3 free fatty acids (ω-3 FFAs) and 1α, 25-dihydroxy-vitamin D₃ (VD₃ ) dramatically enhances cell apoptosis among three subtypes of breast cancer cell lines. Bcl-2 and total PARP protein levels are decreased in combined treatment MCF-7 and SK-BR-3 cells. Caspase signals play a vital role in cell apoptosis induced by combination. Moreover, Raf-MAPK signaling pathway is involved in the apoptosis induction by combination of ω-3 FFAs+VD₃ . These results demonstrate that the induction of cell apoptosis by combined treatment is dependent on different signaling pathways in three subtypes of breast cancer cell lines.