Antiproliferative activity of Tamoxifen, Vitamin D3 and their concomitant treatment

Breast cancer stands out as the most common cancer type among women throughout the world. Especially for the estrogen receptor alpha (ER α +) positive breast cancer cells Tamoxifen has been widely used as an anti-cancer agent. Tamoxifen's mechanism of action is through ER. It binds to the receptor and leads to a conformational change which eventually prevents cancer cells proliferation and survival. In our current study, we aimed to investigate the combination of Tamoxifen with Vitamin D₃ to test whether this combination will enhance the anti-cancer effect of Tamoxifen on breast cancer cells in vitro. Vitamin D₃ has sterol structure and this property enables it to act similar to hormones. Vitamin D Receptor (VDR) has been commonly found in different types of cancer cells including but not limited to breast and prostate cancer cells. Through this receptor Vitamin D₃ acts as an anti-proliferative agent. We examined the proliferation rate, apoptosis and necrosis levels as well as cell cycle progression in MCF-7 breast cancer cell line in the presence of Vitamin D₃ and Tamoxifen to compare the changes with the Tamoxifen treated group. Our results suggest that Tamoxifen was a more potent anti-cancer agent than Vitamin D₃ or its combination with Vitamin D₃ based on cell cycle arrest, apoptosis and cell proliferation levels. This effect in the apoptosis rate and cell cycle stage of the MCF-7 cells were in line with the changes in gene expression profile of P53, BAX and BCL-2. Our results suggest that Tamoxifen by itself is adequate enough and more potent than Vitamin D₃ or its combination with Vitamin D₃ as anti-cancer agent for the breast cancer cells in vitro.