Studies on the effect of Indole 3 Carbinol in regulating HIF1 alpha expression and apoptosis in MCF7 breast cancer cells

Abstract

newlineHypoxia in cancer stimulates HIF-1and#945; that dimerizes with HIF- 1and#946; and induces angiogenesis, by activating vascular endothelial factor (VEGF) gene. Also hypoxia increases the SIRT1 gene expression. Indole-3-carbinol (I3C) is a potent chemopreventive agent with anticancer activities like activation of apoptosis and inhibiting cell proliferation and angiogenesis. The present study is aimed to investigate the role of I3C in modulating HIF-1and#945; and its downstream target genes. newline newlineI3C revealed a significant down-regulation of HIF-1and#945; and VEGF in normoxia and hypoxia groups (p lt 0.011). A significant down-regulation of the expression of SIRT1 and upregulation of BAX was seen in the hypoxic group with I3C treatment. Insilico analysis showed the good score and interactions with I3C at the active site of HIF-1and#945; which suggests the possibility of I3C to be an inhibitor for HIF-1and#945;. I3C treated Chorioallantoic Membrane (CAM) proved that I3C has the potential to inhibit sprouting angiogenesis as noticed in the decrease in vessel length and size (*p lt 0.0001). newline newlineIn hypoxia high HIF-1and#945; levels were seen due to the failure of VHL interaction, blocking ubiquitin-proteasomal degradation. HIF-1and#945; induces transcription of the gene encoding VEGF. I3C has been shown to inhibit VEGF expression by inhibiting HIF-1and#945; expression in a hypoxia. newline newlineIn conclusion, it is evidenced, that hypoxic microenvironment can be regulated by I3C by down-regulating the HIF-1and#945; and its target genes. I3C effectively inhibits cell growth of MCF-7 cells and induces apoptosis under hypoxic condition. newline