Synergistic anticancer effect of combination treatment of vitamin D and pitavastatin on the HCC1937 breast cancer cells

Abstract

Vitamin D (Vit D) has anticancer properties including activating cell senescence inhibiting cancer cell proliferation, inducing apoptotic cell death, and decreasing cancer cell migration. On the other hand, statins showed favorable anticancer activities including anti-survival, anti-proliferation, and anti-migration effects. The current study aimed to investigate the synergistic anticancer effect of Vit D and statins against HCC1937 triple-negative breast cancer cells. The antiproliferative effect was tested by MTT assay after 48 hours of the treatments. Trypan blue test and clonogenic assay were used to test the anti-survival activities of the treatments. The ability of the treatments to inhibit the migration ability was tested by scratch assay. Levels of the cell cycle and apoptotic markers were determined by western blotting. Results of the study revealed that all the tested compounds including Vit D, atorvastatin (Ator), simvastatin (Simv), and pitavastatin (Pita) inhibited HCC1937 breast cancer cell growth with different IC50 values ranging from 4.49-12.95 µM. Combined application of Pita and Vit D showed potent synergistic antiproliferative activities against HCC1937 breast cancer cells. The combined therapy of (1µM Vit D and 2 µM Pita) inhibited HCC1937 cell proliferation by cell cycle arrest and apoptosis as evidenced by increasing p21, p53, and cleaved PARP. Finally, the combined treatment decreased the p-STAT3 level in HCC1937 breast cancer cells. The results of the study can be concluded that the combined treatment of Pita and Vit D has a synergistic anticancer effect against HCC1937 breast cancer cells.