Recent Advances in Chemotherapeutic Implications of Deguelin: A Plant-Derived Retinoid

Abstract

Deguelin, a plant retinoid has emerged to be a promising therapeutic agent in the treatment of different cancers. Recent studies demonstrate that deguelin has potential as an angiogenesis antagonist in malignant and endothelial cells by specifically targeting HGF-c-Met and VEGFVEGFR pathways. It is reported to have profound therapeutic effects in pancreatic cancer by inactivation of the hedgehog (Hh) signalling pathway and suppresses the expression of matrix metalloproteinases such as MMP-2 and MMP-9. The basic underlying mechanisms for deguelin mediated anti- NSCLC effects were uncovered through its induction of elevated intracellular Reactive Oxygen Species (ROS) levels and suppression of the PI3K /Akt-HK2 signalling pathway. Deguelin induces cell apoptosis by targeting various pathways most notably regulating the expression of galectin-1 and binding directly to anti-apoptotic Bcl-2 (B-cell lymphoma 2), Bcl-xl (B-cell lymphoma-extralarge) and Mcl-1 (Myeloid Cell Leukemia Sequence 1) in the hydrophobic grooves thereby liberating BAD and BAX from binding with these proteins. These results derived from the effect of Deguelin on various cancer cell lines have further elucidated its role as a novel anti-tumorigenic agent targeting angiogenesis, apoptosis, cell proliferation and migration for cancer chemoprevention. In this review, an attempt has been made to highlight the potential therapeutic effects of Deguelin in destroying the cancer cells by inhibiting various tumour promoting pathways and its uses as a therapeutic agent alone or in combination.