Comparative study of antioxidants as cancer preventives through inhibition of HIF-1 alpha activity.
HIF-1 α (hypoxia inducible factor-1 α isoform) has been exploited as a target in cancer therapeutics. HIF-1 α is the isoform-2 of HIF-1 α subunit. It is a 735 residues long protein modeled in this study. The HIF-1 α 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 α operates only in presence of free radicals. In the present study, five antioxidants, namely lycopene, ascorbic acid, α-tocopherol, curcumin and curcumin dipiperoyl ester which are potent scavengers of reactive oxygen species (ROS) have been docked to HIF-1 α 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.
Upadhyay
Jyoti
J
Indian Institute of Information Technology, Allahabad, India-211002.
Kesharwani
Rajesh K
RK
Misra
Krishna
K