title: Cinnamon extract reduces VEGF expression via suppressing HIF-1α gene expression and inhibits tumor growth in mice.
abstract: Although many anti-VEGF agents are available for cancer treatment, side effects of these agents limit their application for cancer treatment and prevention. Here we studied the potential use of a diet-based agent as an inhibitor for VEGF production. Using a VEGF reporter assay, our data showed that an extract from cinnamon (CE) was a potent inhibitor of VEGF production in human cancer cells and suggested inhibition might be mediated through the suppression of HIF-1α gene expression and protein synthesis. Furthermore, CE treatment was found to inhibit expression and phosphorylation of STAT3 and AKT, which are key factors in the regulation of HIF-1α expression, and significantly reduce angiogenesis potential of cancer cells by migration assay. Consistent with these results, we observed significant suppression of VEGF expression, blood vessel formation, and tumor growth in a human ovarian tumor model in mice treated with CE. Cinnamaldehyde, a major component in cinnamon, was identified as one active component in CE that inhibits VEGF expression. Taken together, our findings provide a novel mechanism underlying anti-angiogenic and anti-tumor actions of CE and support the potential use of CE in cancer prevention and treatment. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Molecular Medicine, Beckman Research Institute of City of Hope, Duarte, California.|Department of Surgery, Beckman Research Institute of City of Hope, Duarte, California.
authors.forename: Keqiang
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Surgery, Beckman Research Institute of City of Hope, Duarte, California.
authors.forename: Ernest S
authors.initials: ES
authors.lastname: Han
authors.affiliation: Department of Surgery, Beckman Research Institute of City of Hope, Duarte, California.
authors.forename: Thanh H
authors.initials: TH
authors.lastname: Dellinger
authors.affiliation: Department of Molecular Medicine, Beckman Research Institute of City of Hope, Duarte, California.|Department of Surgery, Beckman Research Institute of City of Hope, Duarte, California.
authors.forename: Jianming
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Molecular Medicine, Beckman Research Institute of City of Hope, Duarte, California.
authors.forename: Sangkil
authors.initials: S
authors.lastname: Nam
authors.affiliation: U.S. Department of Agriculture, Diet, Genomics, and Immunology Laboratory, Beltsville Human Nutrition Research Center, Agricultural Research Service, Beltsville, Maryland.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Anderson
authors.affiliation: Department of Surgery, Beckman Research Institute of City of Hope, Duarte, California.
authors.forename: John H
authors.initials: JH
authors.lastname: Yim
authors.affiliation: Department of Molecular Medicine, Beckman Research Institute of City of Hope, Duarte, California.|Department of Surgery, Beckman Research Institute of City of Hope, Duarte, California.
authors.forename: Wei
authors.initials: W
authors.lastname: Wen
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000627:therapeutic use*; D002935:Cinnamomum zeylanicum / Q000737:chemistry*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D016513:Mice, SCID; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010051:Ovarian Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010053:Ovary / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010936:Plant Extracts / Q000737:chemistry / Q000627:therapeutic use; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000235:genetics* / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010936:Plant Extracts; D042461:Vascular Endothelial Growth Factor A
keywords: HIF-1α; VEGF; angiogenesis; cinnamon extract; xenograft