Targeting HIF-1α by Natural and Synthetic Compounds: A Promising Approach for Anti-Cancer Therapeutics Development
Rituparna Ghosh, Priya Samanta, Rupali Sarkar, Souradeep Biswas, Prosenjit Saha, Subhadip Hajra, Arijit Bhowmik
Abstract
Advancement in novel target detection using improved molecular cancer biology has opened up new avenues for promising anti-cancer drug development. In the past two decades, the mechanism of tumor hypoxia has become more understandable with the discovery of hypoxia-inducible factor-1α (HIF-1α). It is a major transcriptional regulator that coordinates the activity of various transcription factors and their downstream molecules involved in tumorigenesis. HIF-1α not only plays a crucial role in the adaptation of tumor cells to hypoxia but also regulates different biological processes, including cell proliferation, survival, cellular metabolism, angiogenesis, metastasis, cancer stem cell maintenance, and propagation. Therefore, HIF-1α overexpression is strongly associated with poor prognosis in patients with different solid cancers. Hence, pharmacological targeting of HIF-1α has been considered to be a novel cancer therapeutic strategy in recent years. In this review, we provide brief descriptions of natural and synthetic compounds as HIF-1α inhibitors that have the potential to accelerate anticancer drug discovery. This review also introduces the mode of action of these compounds for a better understanding of the chemical leads, which could be useful as cancer therapeutics in the future.