title: Chemopreventive effects of Frondanol A5, a Cucumaria frondosa extract, against rat colon carcinogenesis and inhibition of human colon cancer cell growth.
abstract: Sea cucumber extracts have been widely used to treat individuals with inflammatory conditions in East Asia. The present study has been designed to test potential colon cancer-preventive properties of Frondanol A5, a glycolipid extract from the sea cucumber, Cucumaria frondosa, using in vivo and in vitro models of colon cancer. Chemopreventive efficacy of Frondanol A5 was evaluated on azoxymethane-induced rat colon carcinogenesis using colonic aberrant crypt foci (ACF) as efficacy marker. At 7 weeks of age, groups of rats (12 per group) were fed the AIN-76A diet, and ACFs were induced by azoxymethane (15 mg/kg body weight). Three days after azoxymethane treatment, rats were fed with the diets containing 0, 150, and 450 ppm of Frondanol A5 and continued on the diets for 8 weeks, at which time ACFs were evaluated. Expression levels of proliferating cell nuclear antigen and p21(WAF1/CIP1) were determined in ACFs. Further, Frondanol A5 (10-120 microg/mL) was studied for its growth-inhibitory and apoptotic effects in the HCT-116 cell line. Dietary administration of 150 and 450 ppm of Frondanol A5 significantly suppressed azoxymethane-induced total colonic ACF formation, approximately 34% to 55% (P < 0.01 to P < 0.0001), and multicrypt aberrant foci (48-68.5%, P < 0.0001) in a dose-dependent manner. ACFs in rats treated with Frondanol A5 showed significant upregulation of p21(WAF1/CIP1) and downregulation of proliferating cell nuclear antigen compared with control group. Frondanol A5 showed growth inhibition at S and G(2)-M phase with a decrease in Cdc25c and an increase in p21(WAF1/CIP) with significant apoptosis associated with H2AX phosphorylation and caspase-2 cleavage in HCT116 cells. Overall, Frondanol A5 exhibits potential chemopreventive properties for colon carcinogenesis, which suggests further development of this sea cucumber extract.
authors.affiliation: Department of Medicine, University of Oklahoma Cancer Institute, University of Oklahoma Health Sciences Center, Oklahoma City, 73104, USA.
authors.forename: Naveena B
authors.initials: NB
authors.lastname: Janakiram
authors.forename: Altaf
authors.initials: A
authors.lastname: Mohammed
authors.forename: Yuting
authors.initials: Y
authors.lastname: Zhang
authors.forename: Chang-In
authors.initials: CI
authors.lastname: Choi
authors.forename: Carl
authors.initials: C
authors.lastname: Woodward
authors.forename: Peter
authors.initials: P
authors.lastname: Collin
authors.forename: Vernon E
authors.initials: VE
authors.lastname: Steele
authors.forename: Chinthalapally V
authors.initials: CV
authors.lastname: Rao
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects*; D002469:Cell Separation; D018890:Chemoprevention; D003110:Colonic Neoplasms / Q000517:prevention & control*; D048016:Cucumaria / Q000737:chemistry*; D005434:Flow Cytometry; D006017:Glycolipids / Q000494:pharmacology; D045325:HCT116 Cells; D006657:Histones / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D018809:Proliferating Cell Nuclear Antigen; D051381:Rats
chemical_list: D000970:Antineoplastic Agents; D006017:Glycolipids; C468783:H2AX protein, human; D006657:Histones; D018809:Proliferating Cell Nuclear Antigen