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

Academic Article

Abstract

  • 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.
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    Keywords

  • Animals, Antioxidants, Apolipoprotein A-I, Carcinoma, Ovarian Epithelial, Cell Proliferation, Cell Survival, Cell Transformation, Neoplastic, Female, Humans, Mice, Neoplasms, Glandular and Epithelial, Ovarian Neoplasms, Oxidative Stress, Superoxide Dismutase, Up-Regulation
  • Digital Object Identifier (doi)

    Author List

  • Ganapathy E; Su F; Meriwether D; Devarajan A; Grijalva V; Gao F; Chattopadhyay A; Anantharamaiah GM; Navab M; Fogelman AM
  • Start Page

  • 1071
  • End Page

  • 1081
  • Volume

  • 130
  • Issue

  • 5