உயிர் வேதியியல் & பகுப்பாய்வு உயிர்வேதியியல்

சுருக்கம்

Analysis of the Cytotoxic Effects of Vitamin D3 on Colorectal, Breast and Cervical Carcinoma Cell Lines

Shruthi N, Prashanthkumar MV, Venugopalreddy B, Suma MN and Subba Rao VM

Although evidences from epidemiological suggested possible involvement of vitamin D in the prevention and treatment of cancers, it is not fully known how vitamin D inhibits cancer cell growth. Recent studies have shown that 1,25-(OH)2D inhibits cancer cell proliferation by binding to vitamin-D receptor (VDR). The vitamin D - VDR complex in turn (a) upregulate cell cycle inhibitors p21 and p27; (b) promote apoptosis mediators caspase-3 and 7, Bad, p53 and PTEN; (c) arrest cells in senescence phase; (d) elevate cell differentiation; and (e) inhibit IGF signaling. Moreover, vitamin D reduces reactive oxygen species (ROS) there by prevents the progression of cancer cells. However, it is currently unknown whether vitamin D induced cancer cell death is mediated by its effect on ROS destroying Nrf2 signaling. In addition, it is also not known whether withdrawal of glucose improves the efficacy of vitamin D as presence of excess glucose promotes ROS in cancer cells. Therefore, first, efficacy of vitamin D for inhibiting the growth of cell lines HCT116, HeLa and MCF-7 was determined. Next, the effect of vitamin D on Nrf2 expression and activity in the presence and absence of glucose was assessed. The data showed that vitamin D inhibited the growth of HCT116, HeLa and MCF-7 cells in a dose dependent manner with more potency toward HCT116. Vitamin D reduced the levels of Nrf2 and NQO1 expression when HCT116 cells were treated in glucose lacking medium. But, despite a significant reduction in cell viability, no change in the Nrf2 expression was observed if the HCT-116 cells were treated with vitamin D dissolved in high glucose (4.5g/L) containing DMEM. Therefore, it is concluded that the cell growth inhibition by vitamin D, observed in the presence of glucose, is not at least mediated by Nrf2 modulation in HCT116 cells.