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.
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ABSTRACT: Red variants of S. Japonicas show unique ecological characteristics and are indigenous to Jeju Island in South Korea. Various biological activities of red sea cucumber extracts (RSCEs) were evaluated. In comparison with positive controls, anti-oxidant activity of RSCEs was very low. In HL-60 and HT-29 cells, chloroform and ethyl acetate (EtOAc) fractions showed higher than 80 and 60% growth inhibition, respectively. Nuclear condensation and increased pro-apoptotic signaling revealed that RSCEs triggered apoptosis. EtOAc fractions also showed strong anti-inflammatory effects at sub-lethal concentrations in lipolysaccharide-stimulated RAW264.7 cells and suppressed more than 90% of nitric oxide (NO) and prostaglandin 2 productions at 50 μg/mL by inhibiting inducible NO synthase and cydooxygenase-2. Water-soluble fractions showed good antibacterial effects against Staphylococcus aureus and Staphylococcus epidermidis.Journal of the Korean Society for Applied Biological Chemistry 10/2011; 54(5). DOI:10.1007/BF03253150 · 0.54 Impact Factor
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ABSTRACT: This work presents an analysis of current data on the investigation into the functional properties of biologically active substances in model systems based on cultivated human cells. The knowledge regarding the practical application of cell cultures for the analysis of functional properties of bioactive substances is summarized, including antioxidant, immunomodulating, pro- and prebiotics, and chemoprevention properties. The most promising directions in cell culture model development for the investigation of functional properties, including three-dimensional models, are discussed.Applied Biochemistry and Microbiology 11/2012; 48(6). DOI:10.1134/S0003683812060087 · 0.66 Impact Factor
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ABSTRACT: Background: The cytotoxic activity of sea cucumber glycosides against different types of cells and cell lines, including human tumor cell lines, has been studied for many years. However, the molecular mechanism(s) of the antitumor action of triterpene glycosides on cancer cells remain unclear. This article reports a continuation of investigations of triterpene glycoside cucumarioside A2-2 isolated from the Far-Eastern sea cucumber Cucumaria japonica. It describes a study of glycoside anticancer activity in vivo and glycoside interaction with mouse Ehrlich carcinoma cells in vitro. Methods: The cytotoxicity of cucumarioside A2-2 and its effect on apoptosis, the cell cycle, DNA biosynthesis and p53 activity, and glycoside anticancer action against Ehrlich carcinoma cells were studied. Results: Cucumarioside A2-2 influences tumor cell viability at micromolar concentrations. The EC50 for glycoside estimated by nonspecific esterase assay and MTT assay was 2.1 and 2.7 μM, respectively. Cucumarioside A2-2 at a subcytotoxic range of concentrations exhibits a cytostatic effect by blocking cell proliferation and DNA biosynthesis in the S phase. It may induce apoptosis in tumor cells in a caspase-dependent way, bypassing the activation of the p53-dependent segment. Conclusion: The anticancer and proapoptotic properties of cucumarioside A2-2 may be due to direct interaction of the glycoside with tumor cells. The in vivo anticancer effect of cucumarioside A2-2 may be associated with the ability of the drug to arrest the cell cycle in the synthetic phase and induce programmed tumor cell death. © 2013 S. Karger AG, Basel.Chemotherapy 11/2013; 59(3):181-191. DOI:10.1159/000354156 · 1.55 Impact Factor