Autophagy/ Apoptosis Induced by Geraniol through HIF-1α/BNIP3/Beclin-1 Signaling Pathway in A549 CoCl2 Treated Cells

Abstract

Purpose: During cancer growth, hypoxia occurs along with autophagy as an adaptive responseto overcome cellular stress. Geraniol (GE) is a natural isoprenoid known for its wide anticanceractivity and autophagy induction in the cancer cell. To investigate the antihypoxic potential ofGE with the incidence of autophagy and apoptotic cell death in A549 CoCl2 treated cells.Methods: A549 cells were incubated for 24 hours with GE and CoCl2 either alone or incombination. We examined the cytotoxicity and cell viability of GE either alone or incombination therapy using MTT and trypan blue assay.GE modulating effect was determined onlipid peroxidation, antioxidant capacity markers, gene expression levels of hypoxia induciblefactor-1 (HIF-1), NF-κB, vascular endothelial growth factor (VEGF), autophagy factors in differentgroups, besides apoptotic bodies using acridine orange/ethidium bromide (AO/EB).Results: GE and CoCl2 combination therapy downregulated the expression of HIF-1α thatsuppressed A549 cell growth through downregulation of BNIP3 and beclin-1 gene expression.This resulted in autophagy and apoptotic cell death, in addition to the downregulation of NF-kBand VEGF expression. Also, GE treatment significantly reduced the oxidative stress markers andrestored the antioxidant capacity.Conclusion: GE possesses an antihypoxic effect on A549 CoCl2 treated cells and induces celldeath via autophagy along with apoptosis through HIF-1α/BNIP3/beclin-1 signaling pathway.

Keywords: Hypoxia, Geraniol, HIF-1α, Autophagy, BNIP3, Beclin-1, VEGF