HIF-1α & NF-κB downregulation by S-Carvone mitigate hypoxia and inflammation in CoCl2 treated cells

Background: S-CAV is a natural monoterpene that possesses antioxidant, anti-inflammatory, and anticancer activities. Both HIF and NF-κB pathways play a role in the hypoxia and inflammation during cancer progression. Objectives: In this study, we determine the effect of S-CAV against hypoxia-induced by CoCl2 on A549 cells through the relationship between HIF-1α and NF-κB as well as inflammatory cytokines and oxidative stress. Methods: A549 cells were treated with S-CVN and CoCl2 either alone or in combination for 24 hours. Afterward, cytotoxicity, cell viability, and mode of cell death were determined. Different markers were measured to detect the effect of S-CVN on CoCl2 induced oxidative damage (MDA and TAC), hypoxia associated inflammation (IL-6 and TNF-α), as well as HIF-1α and NF-κB gene expression. Results: The results showed that S-CAV and CoCl2 induced cytotoxicity at concentrations 4 and 6.2 mM. S-CAV and CoCl2 combination therapy showed apoptotic cell death and a reduction in oxidative stress markers. Moreover, S-CAV in combination therapy downregulates the mRNA HIF-1α and NF-κB expression that parallels the reduction in IL-6 and TNF-α levels. Conclusion: Therefore, S-CAV possesses an antihypoxic effect on A549 CoCl2 treated cells by reducing the oxidative stress, HIF-1α, and NF-κB gene expression as well as proinflammatory cytokines.