Raddeanin A induced apoptosis of non-small cell lung cancer cells by promoting ROS-mediated STAT3 inactivation.

PURPOSE

Non-small cell lung cancer (NSCLC) is a high-risk type of lung cancer. Raddeanin A exerts anti-tumor activity by regulating cell proliferation and apoptosis, but its role in NSCLC remains to be elucidated. This study was to investigate the effect of raddeanin A in NSCLC and its mechanism.

METHODS

The effect of raddeanin A (2, 4, 8, 10 μmol/L) on the viability, proliferation and apoptosis of A549 and H1299 cells was determined by cell counting kit-8, colony formation and flow cytometry assays, respectively. Next, western blot was performed to examine the protein expressions of cleaved caspase-3, Bax, phosphorylated signal transducer and activator of transcription 3 (p-STAT3) and STAT3. Subsequently, the intracellular reactive oxygen species (ROS) generation and mitochondrial membrane potential of NSCLC cells were detected by 2', 7'-dichlorofluorescein-diacetate (DCFH-DA) and JC-1 assay. Lastly, the effect of N-acetylcysteine (NAC) on the apoptosis, ROS generation, and STAT3 was evaluated by the above-mentioned assays again.

RESULTS

Raddeanin A treatment had no obvious effect on 16HBE cells viability, but it inhibited viability and proliferation of A549 and H1299 cells, promoted the apoptosis, increased the protein expressions of cleaved caspase-3 and Bax, generated intracellular ROS, as well as decreased mitochondrial membrane potential and the expressions of p-STAT3 and STAT3 in A549 and H1299 cells. After cells treated with NAC, the effect of raddeanin A was reversed, as evidenced by the apoptosis and ROS generation were suppressed, and the expression of p-STAT3 was promoted.

CONCLUSION

Raddeanin A suppressed the proliferation and induced apoptosis of NSCLC cells via promoting the ROS-mediated STAT3 inactivation.