Caffeic Acid Phenethyl Ester Induces Apoptosis of Human Pancreatic Cancer Cells Involving Caspase and Mitochondrial Dysfunction

Aims: This study aimed to investigate the effect of caffeic acid phenethyl ester (CAPE), an active component isolated from honeybee propolis, in inducing apoptosis in human pancreatic cancer cells. Methods: Inhibition of viability of BxPC-3 and PANC-1 cell lines induced by CAPE was estimated by a trypan blue dye exclusion test. The type of cell death in BxPC-3 after CAPE treatment was characterized by observation of morphology, sub-GI DNA content, annexin-V/PI staining, caspase-3 and caspase-7 assay, and DNA agarose gel electrophoresis. Results: CAPE (10 μg/ml) resulted in marked inhibition of viability of BxPC-3 (80.4 ± 4.1%) and PANC-1 (74.3 ± 2.9%) cells. CAPE induced a time-dependent increase in hypodiploid percentage and a significant decrease in mitochondrial transmembrane potential in BxPC-3 cells. It induced morphological changes of typical apoptosis, but no DNA fragmentation was noted by DNA electrophoresis. The inhibition of growth and increased in the proportion of sub-G1 cells was partially blocked by pretreatment with the pan-caspase inhibitor Z-VAD-fmk (50 μM) in BxPC-3 cells indicating a caspase-related mechanism in CAPE-induced apoptosis. Caspase-3/caspase-7 activity was approximately 2 times greater in CAPE-treated BxPC-3 cells compared with control cells. Conclusions: These results suggest that CAPE is a potent apoptosis-inducing agent. Its action is accompanied by mitochondrial dysfunction and activation of caspase-3/caSpase-7.