C 16 Saturated Fatty Acid Induced Autophagy in A549 Cells through Topoisomerase I Inhibition

Abstract

C 16 saturated fatty acid (Palmitic acid) is one of the most common dietary fatty acids which played an important role in the cellular biological functions. Palmitic acid (PA) was tested for potential inhibition of DNA topoisomerase I (topo I) and it exhibited inhibitory activity in the nanomolar range. Treatment of lung adenocarcinoma cell line A549 with PA resulted in a decrease in cell viability in a concentration-dependent manner, and PA showed cytotoxicity with an IC 50 value of 150 µM. DNA fragmentation assay and caspase activity indicated that PA does not induce apoptotic cell death in A549 cells. Finally, we found that PA was able to cause an increase in autophagic flux in a time-dependent manner, evidenced by the accumulation of LC3 through monodansylcadaverine (MDC) staining. More importantly, inhibition of autophagy by blocking autophagosome formation via the inhibition of type III Phosphatidylinositol 3-kinases (PI-3K), by 3-Methyladenine (3-MA) was able to effectively suppress PA-induced autophagy. We showed that inhibition of autophagy sensitized the cells signal to PA-induced apoptosis, suggesting the pro-survival function of autophagy induced by PA. Taken together, results from this study reveal that PA as a topo I inhibitor induced autophagic cell death in A549 cells.