Arachidonic acid activates extrinsic apoptotic pathway to enhance tumoricidal action of bleomycin against IMR-32 cells

Bleomycin is a commonly used anti-cancer drug in the management of a variety of cancers. Previously, we showed that arachidonic acid (AA) augmented the growth inhibitory action of bleomycin on IMR-32 (human neuroblastoma cells) in vitro by enhancing oxidative stress. Despite these results, the exact molecular mechanism of cytotoxic action of bleomycin and its augmentation by AA is not known. Our current study revealed that a combination of bleomycin and AA significantly enhanced the expression of FAS gene, which is involved in programmed cell death (apoptosis) and caspases 3 and 8 compared to either bleomycin or AA alone implying that activation of extrinsic apoptotic pathway plays a major role in their (bleomycin + AA) tumoricidal action. It is interesting to note that AA by itself enhanced the expression of FAS and caspases 3 and 8 compared to control. Since caspases have a role in inflammation, cell proliferation, tumour suppression, cell differentiation, neural development and axon guidance and ageing, this may explain pleiotropic actions of AA and their metabolites.