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The Triterpenoid Frondoside A From the Sea Cucumber Cucumaria Frondosa Inhibits Proliferation of Human Pancreatic Cancer Cells In Vivo and In Vitro

Posted on: Tuesday, 21 December 2004, 03:00 CST

The Triterpenoid Frondoside A from the Sea Cucumber Cucumaria frondosa Inhibits Proliferation of Human Pancreatic Cancer Cells In Vivo and In Vitro. X.-Q. Li,* A. Roginsky,* X.-Z. Ding,*[dagger] C. Woodward,** P. Collin,** M. S. Talamonti,*[dagger] R. H. Bell,*[dagger] and T. E. Adrian.*[dagger] * Department of Surgery and [dagger] Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL; and ** Coastside Research, Stonington, ME.

There is a pressing need for effective cancer therapeutics, particularly for organ sites such as the pancreas. Pancreatic cancer is the fourth leading cause of cancer death in the United States and prognosis is dismal

. Pancreatic cancer cells are resistant to most existing and novel chemotherapeutics. Furthermore, finding agents that will inhibit growth, invasion, and metastases of pancreatic cancers will undoubtedly be valuable for treating other malignancies. We have identified a triterpenoid, frondoside A from Cucumaria frondosa, that has potent growth inhibitory effects on pancreatic and other cancer cells. For example, in the highly malignant human pancreatic cancer cell line, AsPC-1, frondoside A inhibits DNA synthesis by >90% and blocks the increase in cell number at a concentration of 5 g/mL. Frondoside A induces apoptosis as evidenced by morphological changes, annexin V binding, and terminal deoxynucleotide transferase-mediated nick end labeling (TUNEL assay). Growth inhibition was accompanied by marked increases in the expression of the cyclin-dependent kinase inhibitors p21 and p27. The frondoside-induced apoptosis was characterized by a marked increase in expression of the proapoptotic protein Bax and decreases in expression of the antiapoptotic proteins Bcl-2 and Mcl-1. Frondoside A also induced activation by cleavage of the activator caspase 9 and the executioner caspases 3 and 7 and markedly inhibited the growth of AsPC-1 cell xenografts in athymic mice at a dose of only 10 g . kg^sup -1^ . d^sup -1^. In conclusion, frondoside A has potent antiproliferative and apoptosis-inducing effects on human pancreatic cancer. This triterpenoid is likely to be valuable for the treatment or chemoprevention of this and other cancers. Copyright American Institute of Nutrition Dec 2004

Source: Journal of Nutrition, The

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