Baicalin potentiates TRAIL-induced apoptosis through p38 MAPK activation and intracellular reactive oxygen species production

The combination of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) with other agents has been recognized as a promising strategy to overcome TRAIL resistance in cancer cells. Baicalin (5, 6-dihydroxy-7-o-glucuronide flavone) is a flavonoid from the root of the medicinal herb Scutellaria baicalensis Georgi, which has been reported to exert antioxidant, anti-inflammatory, antiviral and anticancer activities in vitro. However, the effect of baicalin on TRAIL-induced cytotoxicity has not been previously reported. In the present study, the effect of combining TRAIL and baicalin was investigated in non-small cell lung cancer cell lines. The results revealed that baicalin was able to sensitize A549 and H2009 cells to TRAIL-induced apoptosis. This was detected by the potentiation of poly-adenosine-5'-diphosphate-ribose polymerase cleavage and Annexin V-fluorescein isothiocyanate staining of cells co-treated with baicalin and TRAIL. In addition, p38 mitogen-activated protein kinase was activated in baicalin and TRAIL co-treated cancer cells, whereas the p38 inhibitor SB203580 effectively suppressed cell death within the co-treated cells. Butylated hydroxyanisole and N-acetyl-cysteine, known reactive oxygen species (ROS) scavengers, significantly suppressed the potentiated cytotoxicity induced by baicalin and TRAIL co-treatment. The present study is the first, to the best of our knowledge, to demonstrate that baicalin enhances the anticancer activity of TRAIL via p38 activation and ROS accumulation, and may be exploited for anticancer therapy.