title: D-4F, an apoA-I mimetic peptide, inhibits proliferation and tumorigenicity of epithelial ovarian cancer cells by upregulating the antioxidant enzyme MnSOD.
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.
authors.affiliation: Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Ekambaram
authors.initials: E
authors.lastname: Ganapathy
authors.forename: Feng
authors.initials: F
authors.lastname: Su
authors.forename: David
authors.initials: D
authors.lastname: Meriwether
authors.forename: Asokan
authors.initials: A
authors.lastname: Devarajan
authors.forename: Victor
authors.initials: V
authors.lastname: Grijalva
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Arnab
authors.initials: A
authors.lastname: Chattopadhyay
authors.forename: G M
authors.initials: GM
authors.lastname: Anantharamaiah
authors.forename: Mohamad
authors.initials: M
authors.lastname: Navab
authors.forename: Alan M
authors.initials: AM
authors.lastname: Fogelman
authors.forename: Srinivasa T
authors.initials: ST
authors.lastname: Reddy
authors.forename: Robin
authors.initials: R
authors.lastname: Farias-Eisner
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D016632:Apolipoprotein A-I / Q000494:pharmacology*; D000077216:Carcinoma, Ovarian Epithelial; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D005260:Female; D006801:Humans; D051379:Mice; D009375:Neoplasms, Glandular and Epithelial / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000473:pathology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D013482:Superoxide Dismutase / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D000975:Antioxidants; D016632:Apolipoprotein A-I; C465468:D-4F peptide; D013482:Superoxide Dismutase