Antitumor activity of paederosidic acid in human non-small cell lung cancer cells via inducing mitochondria-mediated apoptosis

This study was aimed to investigate antitumor activity of paederosidic acid (PA) in human non-small cell lung Cancer cells and explore the related mechanisms. The anti-proliferative effects of PA on A549 cells were evaluated by MTT method and the IC₅₀ values were calculated. Furthermore, the PA-induced Apoptosis in A549 cells was determined by fluorescence microscope via staining with DAPI and by flow cytometer via staining with FITC conjugated Annexin V/PI. The expression of apoptosis-related or signaling proteins was investigated by Western blotting. Our results demonstrated that PA showed significant anti-tumor activity on lung Cancer in vitro; the mechanisms were involved in inducing mitochondria-mediated Apoptosis via up-regulation of Caspase-3, Caspase-8, caspase-9, Bid, Bax, down-regulation of Bcl-2 and stimulating the release of Cyto-C from mitochondria. In addition, JNK phosphorylation levels significantly increased concomitantly with decrease in Akt phosphorylation after treatment with PA in A549 cells. However, JNK siRNA-transfected cells diminished PA-induced Caspase-3, 8 and 9, Bid and Bax activaton while enhanced the Bcl-2 activation. Collectively, these results indicated that PA-induced JNK activation played an important functional role in Apoptosis.