Anti-pancreatic cancer effects of a polar extract from the edible sea cucumber, Cucumaria frondosa.
OBJECTIVE
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, 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 p21 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 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.
Roginsky
Alexandra B
AB
Department of Surgery and Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Ding
Xian-Zhong
XZ
Woodward
Carl
C
Ujiki
Michael B
MB
Singh
Brahmchetna
B
Bell
Richard H
RH
Collin
Peter
P
Adrian
Thomas E
TE
D000818:Animals; D017302:Annexins / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects*; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D045424:Complex Mixtures / Q000494:pharmacology*; D048016:Cucumaria; D006801:Humans; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D010766:Phosphorylation; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
D017302:Annexins; D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D045424:Complex Mixtures; C552590:Frondanol-A5P; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3