Pumilaside A from Litchi semen induces apoptosis in human gastric cancer BGC823 cells via activation of death receptor- and mitochondria-mediated apoptotic pathways

Purpose:To investigate the cytotoxic effect of pumilaside A from Litchi semen against human gastric cancer BGC823 cells, and unravel its possible mechanism(s) of action. Methods: The cytotoxic activity of pumilaside A (5 - 40 mu g/mL) against BGC823 cells was assessed by thiazolyl blue tetrazolium bromide assay. The pro-apoptotic effect of PA (10, 20 or 40 mu g/mL) on BGC823 cells was monitored by flow cytometry, while the mechanisms involved were investigated using western blot. Results: Pumilaside A significantly produced cytotoxic activity against BGC823 cells (IC50 = 25.43 mu g/mL) and induced apoptosis in BGC823 cells (p < 0.01). Treatment with pumilaside A led to significant upregulation of pro-apoptotic factors (Fas, FasL, FADD, Bax, Apaf-1, and c-caspase -8, 9 and 10), and downregulation of anti-apoptotic factors (survivin and Bcl-2, p < 0.05, 0.01). In addition, pumilaside A increased the cytoplasmic levels of Smac and cytochrome c in BGC823 cells by enhancing their mitochondrial release, and significantly upregulated the levels of executioner c-caspases-3, 6 and 7 (p < 0.05, 0.01). Conclusion: Pumilaside A shows good cytotoxic activity against BGC823 cells via a mechanism related to activation of death receptor- and mitochondria-mediated apoptotic pathways. Thus, pumilaside A has a potential for use as an anti-gastric cancer agent.