D-4F, an apoA-I mimetic peptide, inhibits proliferation and tumorigenicity of epithelial ovarian cancer cells by upregulating the antioxidant enzyme MnSOD
Ekambaram Ganapathy
Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
Search for more papers by this authorFeng Su
Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
Search for more papers by this authorDavid Meriwether
Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
Search for more papers by this authorAsokan Devarajan
Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
Search for more papers by this authorVictor Grijalva
Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
Search for more papers by this authorFeng Gao
Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
Search for more papers by this authorArnab Chattopadhyay
Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
Search for more papers by this authorG.M. Anantharamaiah
Department of Medicine, University of Alabama at Birmingham, Birmingham, AL
A.M.F., M.N., G.M.A. and S.T.R. are principals in Bruin Pharma.
Search for more papers by this authorMohamad Navab
Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
A.M.F., M.N., G.M.A. and S.T.R. are principals in Bruin Pharma.
Search for more papers by this authorAlan M. Fogelman
Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
A.M.F., M.N., G.M.A. and S.T.R. are principals in Bruin Pharma.
A.M.F. is an officer of Bruin Pharma.
Search for more papers by this authorCorresponding Author
Srinivasa T. Reddy
Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA
Te l.: 310-206-3915, Fax: +310-206-3605
A.M.F., M.N., G.M.A. and S.T.R. are principals in Bruin Pharma.
Srinivasa T. Reddy, Department of OB/GYN, Medicine, and Molecular and Medical Pharmacology, University of California Los Angeles, 650 Charles E. Young Drive South, MRL 3736 Los Angeles, CA 90095, USA
Robin Farias-Eisner, Department of OB/GYN, University of California Los Angeles, 650 Charles E. Young Drive South, CHS 24-127, Los Angeles, CA 90095, USA
Search for more papers by this authorCorresponding Author
Robin Farias-Eisner
Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
Tel.: 310-794-1919, Fax: +310-206-3670
Srinivasa T. Reddy, Department of OB/GYN, Medicine, and Molecular and Medical Pharmacology, University of California Los Angeles, 650 Charles E. Young Drive South, MRL 3736 Los Angeles, CA 90095, USA
Robin Farias-Eisner, Department of OB/GYN, University of California Los Angeles, 650 Charles E. Young Drive South, CHS 24-127, Los Angeles, CA 90095, USA
Search for more papers by this authorEkambaram Ganapathy
Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
Search for more papers by this authorFeng Su
Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
Search for more papers by this authorDavid Meriwether
Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
Search for more papers by this authorAsokan Devarajan
Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
Search for more papers by this authorVictor Grijalva
Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
Search for more papers by this authorFeng Gao
Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
Search for more papers by this authorArnab Chattopadhyay
Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
Search for more papers by this authorG.M. Anantharamaiah
Department of Medicine, University of Alabama at Birmingham, Birmingham, AL
A.M.F., M.N., G.M.A. and S.T.R. are principals in Bruin Pharma.
Search for more papers by this authorMohamad Navab
Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
A.M.F., M.N., G.M.A. and S.T.R. are principals in Bruin Pharma.
Search for more papers by this authorAlan M. Fogelman
Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
A.M.F., M.N., G.M.A. and S.T.R. are principals in Bruin Pharma.
A.M.F. is an officer of Bruin Pharma.
Search for more papers by this authorCorresponding Author
Srinivasa T. Reddy
Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA
Te l.: 310-206-3915, Fax: +310-206-3605
A.M.F., M.N., G.M.A. and S.T.R. are principals in Bruin Pharma.
Srinivasa T. Reddy, Department of OB/GYN, Medicine, and Molecular and Medical Pharmacology, University of California Los Angeles, 650 Charles E. Young Drive South, MRL 3736 Los Angeles, CA 90095, USA
Robin Farias-Eisner, Department of OB/GYN, University of California Los Angeles, 650 Charles E. Young Drive South, CHS 24-127, Los Angeles, CA 90095, USA
Search for more papers by this authorCorresponding Author
Robin Farias-Eisner
Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
Tel.: 310-794-1919, Fax: +310-206-3670
Srinivasa T. Reddy, Department of OB/GYN, Medicine, and Molecular and Medical Pharmacology, University of California Los Angeles, 650 Charles E. Young Drive South, MRL 3736 Los Angeles, CA 90095, USA
Robin Farias-Eisner, Department of OB/GYN, University of California Los Angeles, 650 Charles E. Young Drive South, CHS 24-127, Los Angeles, CA 90095, USA
Search for more papers by this authorA.M.F. is an officer of Bruin Pharma.
Te l.: 310-206-3915, Fax: +310-206-3605
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.
Supporting Information
Additional Supporting Information may be found in the online version of this article.
| Filename | Description |
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| IJC_26079_sm_suppfigure1.tif25.8 MB | Supporting Figure 1. |
| IJC_26079_sm_suppfigure2.tif25.8 MB | Supporting Figure 2. |
| IJC_26079_sm_suppfigure3.tif25.8 MB | Supporting Figure 3. |
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