Effect of capecitabine and melatonin on HER2+ (SK-BR-3) and HER2- (MCF7) human breast cancer cell lines

Abstract

Purpose: To determine the effect of melatonin in combination with capecitabine on the proliferation and induction of apoptosis in MCF-7 and SK-BR-3 breast cancer cell lines. Methods: The MTT assay (3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide) was performed to investigate the effect of capecitabine and in combination with melatonin on cell lines and to determine the half-maximal concentration (IC50) and combination index. Expression of apoptotic markers, Bax, Bcl-2, and caspase-3 were measured by polymerase chain reaction (PCR) after treatment. Results: The IC50 of melatonin and capecitabine in MCF-7 and SK-BR-3 cell lines were 4.52 mM and 619.36 µg/mL, and 5.1 mM and 679.51 µg/mL, respectively. The combined use of melatonin and capecitabine significantly reduced IC50. Also, combination index (CI) values were < 1, indicating that the combination of capecitabine and melatonin has a synergistic effect. The results of gene expression also showed enhancement in the Bax/Bcl-2 ratio in melatonin-capecitabine combination compared with capecitabine alone in both cell lines. Conclusion: Melatonin-capecitabine-induced cell death is controlled by caspase-3 and Bax/Bcl-2- dependent apoptosis. The combination of melatonin and capecitabine has a synergistic effect on both HER2+ and HER2- cells.