title: HDL mimetics inhibit tumor development in both induced and spontaneous mouse models of colon cancer.
abstract: Recent studies suggest that high-density lipoprotein (HDL) levels are inversely related to colon cancer risk. HDL mimetics constructed from a number of peptides and proteins with varying structures possess anti-inflammatory and antioxidant properties reminiscent of HDL. In this article, we examined whether HDL mimetics, L-4F (an apolipoprotein A-I mimetic peptide) and G* (an apolipoprotein J mimetic peptide) affect tumor growth and development in mouse models of colon cancer. HDL mimetics reduced viability and proliferation of CT26 cells, a mouse colon adenocarcinoma cell line, and decreased CT26 cell-mediated tumor burden in BALB/c mice when administered subcutaneously or orally. Plasma levels of lysophosphatidic acid (LPA), a serum biomarker for colon cancer, were significantly reduced in mice that received HDL mimetics, suggesting that binding and removal of proinflammatory lipids is a potential mechanism for the inhibition of tumor development by HDL mimetics. Furthermore, L-4F significantly reduced size and number of polyps in APC(min/+) mice, a mouse model for human familial adenomatous polyposis, suggesting that HDL mimetics are effective in inhibiting the development of both induced and spontaneous cancers of the colon. Our results, for the first time, identify HDL mimetics as a novel therapeutic strategy for the treatment of colon cancer.
authors.affiliation: Department of Obstetrics and Gynecology, University of California Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Su
authors.forename: Victor
authors.initials: V
authors.lastname: Grijalva
authors.forename: Kaveh
authors.initials: K
authors.lastname: Navab
authors.forename: Ekambaram
authors.initials: E
authors.lastname: Ganapathy
authors.forename: David
authors.initials: D
authors.lastname: Meriwether
authors.forename: Satoshi
authors.initials: S
authors.lastname: Imaizumi
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; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D016632:Apolipoprotein A-I / Q000737:chemistry*; D051152:Clusterin / Q000737:chemistry*; D003106:Colon / Q000473:pathology; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D008075:Lipoproteins, HDL / Q000737:chemistry*; D008246:Lysophospholipids / Q000097:blood; D008297:Male; D051379:Mice; D018716:Molecular Mimicry; D009368:Neoplasm Transplantation; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D016632:Apolipoprotein A-I; D051152:Clusterin; C472885:L-4F peptide; D008075:Lipoproteins, HDL; D008246:Lysophospholipids; D010455:Peptides; C032881:lysophosphatidic acid