Antitumor activity of curcumin by modulation of apoptosis and autophagy in human lung cancer A549 cells through inhibiting PI3K/Akt/mTOR pathway

Curcumin is known to exhibit anticancer effects on various cancers with selective cytotoxicity in tumor cells. In the present study, the effects of curcumin-induced multiple PCDs on human non-small cell lung cancer (NSCLC) cells and the potential molecular mechanisms of apoptosis and autophagy triggered by curcumin via the PI3K/Akt/mTOR signaling pathway were explored, further confirmed by co-culture of curcumin with mTOR blocker rapamycin and PI3K/Akt inhibitor LY294002. The anti-proliferation effect of different stimulus was measured by MTT assay. Apoptosis was detected by flow cytometry. Autophagy induction was detected by MDC labeling and western blotting of Beclin1, LC3, and p62 expression. The mRNA and protein expression levels of Akt and mTOR were assayed by real-time fluorescence quantitative (qRT-PCR) technique and western blotting. Our results showed that curcumin inhibited the viability of A549 cells time- and dose-dependently. In addition, a dosage-dependent A549 cell apoptosis-induction phenomena was observed by the curcumin intervention. Moreover, obvious autophagy was induced after curcumin-treatment, characterized by the formation of fluorescent particles [autophagic vesicles (AVs)] and significant increase in ratio of LC3-II/LC3-I and Beclin1 as well as decreased p62 expression. Furthermore, the effect of curcumin on a substantial downregulation of phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway was observed. It is worth noting that the inhibition of mTOR by rapamycin or of PI3K/Akt by LY294002 augmented curcumin-induced apoptosis and autophagy, leading to significant inhibition of cell proliferation. From these findings, it can be speculated that curcumin potently inhibit the cell growth of NSCLC A549 cells through inducing both apoptosis and autophagy by inhibition of the PI3K/Akt/mTOR pathway. These results support the potential use of curcumin as a novel candidate in treatment of human lung cancer.