Role of natural secondary metabolites as HIF-1 inhibitors in cancer therapy

Hypoxia-inducible Factor 1 (HIF-1) is a transcriptional activator that intervenes in versatile reactions to hypoxia. Natural drugs, widely distributed in plants, comprise many metabolites, possessing their potential as anti-cancer agents. Studies have highlighted HIF-1 as a potential pharmacological target for cancer therapy. Secondary metabolites derived from natural products (plant-derived or marine organisms) with unique chemical structures have demonstrated HIF-1 inhibition. Ganetespib, topotecan, PX-478, aminoflavone, fluorine-19-fluoroded xyglucose, etc. have entered clinical phases of evaluation for different types of cancer. The present work describes role of HIF-1 in tumor progression, summarizes plant based inhibitors such as berberine, rohitukine, harringtonine, acronycin, nuciferine, evodiamine, matrine, etc. Some of the major categories with HIF-1 inhibitory potential are alkaloids, flavonoids, steroids, etc. The manuscript aims to benefit the discovery and development of anti-cancer therapeutics from natural compounds.