Comparative study of antioxidants as cancer preventives through inhibition of HIF-1 alpha activity

HIF-1 alpha (hypoxia inducible factor-1 alpha isoform) has been exploited as a target in cancer therapeutics. HIF-1 alpha is the isoform-2 of HIF-1 alpha subunit. It is a 735 residues long protein modeled in this study. The HIF-1 alpha is absolutely critical for continued survival of cancer cells as it is involved in the activation of glycolysis and it helps an oxygen-starved cell convert sugar to energy without using oxygen. It also initiates angiogenesis to bring in a fresh oxygen supply. HIF-1 alpha operates only in presence of free radicals. In the present study, five antioxidants, namely lycopene, ascorbic acid, alpha-tocopherol, curcumin and curcumin dipiperoyl ester which are potent scavengers of reactive oxygen species (ROS) have been docked to HIF-1 alpha modeled protein in order to assess their binding and consequently, their inhibitory activity. The binding energy score has been found to be in the order, curumin dipiperoyl ester > lycopene > curcumin > tocopherol > ascorbic acid. However, subsequent experiments should be designed to validate these observations.