Anti-pancreatic cancer effects of a polar extract from the edible sea cucumber, cucumaria frondosa

Objectives: To investigate the effects and mechanism of Frondanol-A5P, a polar extract from Cucumaria frondosa, on growth inhibition and apoptosis in S2013 and AsPC-1 human pancreatic cancer cells. Methods: The effects of Frondanol-A5P on proliferation, cell cycle, expression of cell cycle proteins and p21^waf1, phosphorylation of MAP kinases, annexin V binding, and caspase-3 activation were examined. Results: Frondanol-A5P inhibited proliferation and induced G2/M phase cell cycle arrest in both cell lines with decreased expression of cyclin A, cyclin B, and cdc25c. Frondanol-A5P induced phosphorylation of stress-activated protein kinase and Janus kinase (SAPK/JAK) and p38 mitogen-activated protein kinase (MAP) within 5 minutes. Frondanol-A5P markedly increased expression of ^waf1 messenger RNA and protein at 3 hours in both cell lines. This effect was reduced by the p38 kinase inhibitor, SB203580. Frondanol-A5P markedly increased annexin V binding and activated caspase-3. Conclusions: Frondanol-A5 causes cell cycle arrest and apoptosis in human pancreatic cancer cells. These changes are associated with decreased expression of cyclin A, cyclin B, and cdc25c and increased expression of p21^waf1 that, at least in part, is mediated by a p38 kinase-dependent mechanism. Because Frondanol-A5P is derived from an edible, nontoxic, sea cucumber, it may be valuable for nutritional therapy or prevention of pancreatic cancer.