Bufotalin Promotes TRAIL-induced Apoptosis in Non-Small Lung Cancer Cells
- Pornthip Waiwut1*, Chantana Boonyarat2
- International Journal of Technical Research and Applications
- Research article (Inter)
Abstract— This study investigates the effects of bufotalin, a bufodienolides compound isolated from toad venom, on sensitizing TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis of non-small lung cancer cell lines, A549 and PC-9. Cells were treated with bufotalin in the presence and absence of TRAIL. The cells viability was observed using WST-1(4-[3-(4-iodophenyl)-2-(4-nitrophenyl)2H-5-tetrazolio]-1, 3-benzene disulfonate) assay. The TRAIL-induced apoptotic signaling proteins were examined by immunoblotting. The results showed that TRAIL alone showed potent cytotoxicity on PC-9 cells, but weakly induced the death of the A549 cells, indicating that A549 cells are a TRAIL-resistance cell line and PC-9 cells are a TRAIL-sensitive cell line. Bufotalin significantly enhanced death receptor 4-(DR4) induced cell death in the A549 cell line through the activation of caspase-3 and PARP-1. The combination of bufotalin with TRAIL resulted in the down-regulation of Bid, c-FLIP, and the up-regulation of DR4, RB and p53. In contrast, TRAIL dramatically induced cell death and bufotalin has no effect on TRAIL-induced PC-9 cell death. The results indicate that bufotalin sensitizes the A549 cells, but not the PC-9 cells to TRAIL-induced apoptosis through DR4-induced apoptotic pathway.
Index Terms— TRAIL, Bufotalin, DR4, Bid, apoptosis.