Bovine HDL and Dual Domain HDL-Mimetic Peptides Inhibit Tumor Development in Mice

Feng Su; Anantharamaiah Gm; Mayakonda N Palgunachari; C Roger White; Holly Stessman; Yanyuan Wu; Jay Vadgama; Richard Pietras; Dorothy Nguyen; Srinivasa T Reddy; Robin Farias-Eisner

doi:10.17303/jcrto.2020.8.101

Bovine HDL and Dual Domain HDL-Mimetic Peptides Inhibit Tumor Development in Mice

J Cancer Res Ther Oncol. 2020;8(1):101. doi: 10.17303/jcrto.2020.8.101. Epub 2020 Jan 17.

Authors

Feng Su¹, Anantharamaiah Gm², Mayakonda N Palgunachari², C Roger White², Holly Stessman³, Yanyuan Wu^{4

5}, Jay Vadgama^{5

6}, Richard Pietras^{6

7}, Dorothy Nguyen⁷, Srinivasa T Reddy^{1

6

7

8}, Robin Farias-Eisner^{1

9

10}

Affiliations

¹ Department of Obstetrics and Gynecology, David Geffen School of Medicine, the University of California at Los Angeles, Los Angeles, CA 90095, USA.
² Department of Medicine, the University of Alabama at Birmingham, Birmingham, AL 35294, USA.
³ Department of Pharmacology, Creighton University Medical School, Omaha, NE 68178, USA.
⁴ Division of Cancer Research and Training, Charles R. Drew University of Medicine and Science, Los Angeles, CA 90059, USA.
⁵ Department of Internal Medicine, Charles Drew University, Los Angeles, CA 90059, USA.
⁶ Jonsson Comprehensive Cancer Center, the University of California at Los Angeles, Los Angeles, CA 90095, USA.
⁷ Department of Medicine, Division of Cardiology, David Geffen School of Medicine, the University of California at Los Angeles, Los Angeles, CA 90095, USA.
⁸ Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, the University of California at Los Angeles, Los Angeles, CA 90095, USA.
⁹ Department of Obstetrics, Gynecology, School of Medicine, Creighton University, Omaha, NE 68178, USA.
¹⁰ Hereditary Cancer Center, School of Medicine, Creighton University, Omaha, NE 68178, USA.

Abstract

A growing body of literature supports the role of apolipoproteins present in HDL in the treatment of pro-inflammatory diseases including cancer. We examined whether bovine HDL (bHDL) and three dual-domain peptides, namely AEM-28 and its analog AEM-28-2, and HM-10/10, affect tumor growth and development in mouse models of ovarian and colon cancer. We demonstrate that bHDL inhibits mouse colorectal cancer cell line CT26-mediated lung tumor development, and mouse ovarian cancer cell line ID8-mediated tumor burden. We also demonstrate that, although to different degrees, dual-domain peptides inhibit cell viability of mouse and human ovarian and colon cancer cell lines, but not that of normal human colonic epithelial cells or NIH3T3 mouse fibroblasts. Dual-domain peptides administered subcutaneously or in a chow diet decrease CT26 cell-mediated tumor burden, tumor growth, and tumor dissemination in BALB/c mice. Plasma levels of lysophosphatidic acid (LPA) are significantly reduced in mice that received bHDL and the dual-domain peptides, suggesting that reduction by effecting accumulation and/or synthesis of pro-inflammatory lipids may be one of the mechanisms for the inhibition of tumor development by bHDL and the dual-domain peptides. Our studies suggest that therapeutics based on apolipoproteins present in HDL may be novel agents for the treatment of epithelial adenocarcinomas of the ovary and colon.

Keywords: Cancer Therapeutics; Colon Cancer; HDL; LPA; Mimetic Peptides; Ovarian Cancer.

Abstract

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