D-4F, an apoA-I mimetic peptide, inhibits proliferation and tumorigenicity of epithelial ovarian cancer cells by upregulating the antioxidant enzyme MnSOD

• Published in: International journal of cancer 2012-03, Vol.130 (5), p.1071-1081
• Main Authors: Ganapathy, Ekambaram, Su, Feng, Meriwether, David, Devarajan, Asokan, Grijalva, Victor, Gao, Feng, Chattopadhyay, Arnab, Anantharamaiah, G.M., Navab, Mohamad, Fogelman, Alan M., Reddy, Srinivasa T., Farias-Eisner, Robin
• Format: Article
• Language: English
• Subjects: animal models; Animals; Antioxidants; Antioxidants - pharmacology; apolipoprotein A-I; Apolipoprotein A-I - pharmacology; Biological and medical sciences; Cancer; Carcinoma, Ovarian Epithelial; Cell Proliferation - drug effects; Cell Survival - drug effects; Cell Transformation, Neoplastic - drug effects; epithelial ovarian cancer; Female; Female genital diseases; Gene expression; Gynecology. Andrology. Obstetrics; Humans; Medical research; Medical sciences; Mice; mimetic peptides; MnSOD; Neoplasms, Glandular and Epithelial - pathology; Ovarian cancer; Ovarian Neoplasms - pathology; oxidative stress; Oxidative Stress - drug effects; Oxidative Stress - physiology; Rodents; Superoxide Dismutase - metabolism; Tumors; Up-Regulation
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.26079

We recently reported that apoA‐I and apoA‐I mimetic peptides prevent the development of flank tumors in immunocompetent C57BL/6J mice. To delineate the mechanism(s) of action of apoA‐I mimetic peptides in tumor development, we examined the effect of D‐4F (an apoA‐I mimetic peptide) on the antioxidant status and on the gene expression and function of antioxidant enzymes in ID8 cells (a mouse epithelial ovarian cancer cell line) and in a mouse model. We demonstrate that D‐4F treatment significantly reduces the viability and proliferation of ID8 cells, with a concomitant improvement of the antioxidant status of ID8 cells as measured by lipid peroxidation, protein carbonyl, superoxide anion, and hydrogen peroxide levels. D‐4F treatment induces MnSOD (but not CuZnSOD) mRNA, protein, and activity. Inhibition of MnSOD in ID8 cells using shRNA vectors abrogates the inhibitory effects of D‐4F on ID8 cell viability and proliferation. Moreover, tumor development from ID8 cells carrying shRNA for MnSOD were unaffected by D‐4F treatment. Our results suggest that the inhibitory effects of D‐4F on ID8 cell proliferation and tumor development are mediated, at least in part, by the induced expression and activity of MnSOD.