Resveratrol has many biological effects, including anti-tumor, antiviral 
activities, and vascular protection. Recent studies have suggested that 
resveratrol exert its antitumor effects through induction of autophagy by an 
unknown mechanism. In this study, we investigated the involvement of autophagy 
in resveratrol-induced cell death and its potential molecular mechanisms in A549 
human lung adnocarcinoma cells. Resveratrol-induced growth inhibition and cell 
death was assessed by MTT and clonogenic assays. Activation of autophagy was 
characterized by monodansylcadaverine, transmission electron microscopy, and 
expression of autophagy marker protein LC3. Western blot analysis was used to 
study the cell signals involved in the mechanisms of autophagic death. 
Intracellular free calcium was detected with Fura2-AM staining. Our results 
indicated that resveratrol induced A549 cell death was mediated by autophagy. 
3-methyladenine, an inhibitor of autophagy, suppressed resveratrol-induced 
autophagic cell death, and knockdown of autophagy-related genes Atg5 and 
Beclin-1 with siRNAs reversed RSV-induced cell death. Intracellular free calcium 
accumulated immediately following resveratrol addition, which led to the 
activation of phospho-AMPK and phospho-Raptor, and a reduction in the amount of 
phospho-p70S6K. These effects could be reversed by the AMPK inhibitor compound 
C, and the calcium ion-chelating agent EGTA. In conclusion, we demonstrate that 
resveratrol-induced A549 cell death was mediated by the process of autophagic 
cell death via Ca(2+)/AMPK-mTOR signaling pathway.