Studying the in Silico Effect of Ellagic Acid on HIF-2α to Improve Efficacy of Anticancer Therapy

Journal of Environmental Pathology, Toxicology and Oncology : Official Organ of the International Society for Environmental Toxicology and Cancer
Vidhula AhireKaushala Prasad Mishra

Abstract

The hypoxic tumor microenvironment is one of the major causes of the enhanced chemoresistant and radioresistant behavior of cancer cells. Therefore, the hypoxia-induced factor (HIF) pathway can be endorsed, for not only the malignant phenotype of the cells, but also its metastatic potential. Many drugs targeting the HIF pathways have failed in the clinical setting to demonstrate therapeutic efficacy. Such failures occur due to lack of specificity or redundancy in the complexity of tumor signaling/metabolism that can overcome the inhibitory effects. Another important factor is the letdown of the compound that can be accredited to lack of patient selection in the trials. Although many clinical trials have evaluated the efficacy of anticancer therapeutics and examined their effects on HIF levels, patients were not selected based on their HIF expression levels. If patients do not have elevated levels of HIF, then the therapeutics that target the HIF pathway may be less effective. In the present work, we have targeted HIF-2α of the HIF pathway. Ellagic acid (EA), a well-known anticancer compound and radiosensitizer, is used to inhibit the activity of HIF-2α. Our results show a very unique binding of EA with HIF-2α. Such new agents s...Continue Reading

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