title: Potent anti-angiogenic and cytotoxic effect of conferone on human colorectal adenocarcinoma HT-29 cells.
abstract: BACKGROUND
  Cancer is one of the leading causes of death worldwide, both in developed and developing countries. Of note, colorectal adenoma encompasses a high rate of gastrointestinal-associated cancer death in human being. Today, different strategies, including surgery approaches, photodynamic therapy, radiation and particularly natural compounds have been extensively used to manage tumor behavior in human body.
  
  
  METHODS
  The objective of the present study was to elucidate the multilateral effects of conferone on HT-29 cell lines. In addition to cell cytotoxicity, the extent of lipid peroxidation, MDA formation, catalase, superoxide dismutase and intracellular ROS levels, as markers of oxidative stress, were also studied. P-glycoprotein-mediated cellular efflux effectiveness, anti-angiogenic and finally anti-migratory capacities of conferone-exposed HT-29 cells were monitored over a course of 72 h.
  
  
  RESULTS
  It was found that, conferone mediated cell proliferation arrest and induced cell death through both apoptosis and necrosis phenomena. HT-29 cells, exposed to 20 µM conferone, under gone oxidative stress and total content of reactive oxygen species was increased in a time-dependent manner. Intracellular accumulation of rhodamine 123 and cell's swelling under iso- and hypo-osmotic conditions could be related to P-glycoprotein incorrect performance in the presence of conferone. A significant reduction in CD31 positive cells population and in vitro tubulogenesis of endothelial cells was also observed after incubation with conditioned medium collected from 72 h conferone-treated HT-29 cells. Conferone also precluded angiogenesis capability of treated HT-29 cells through an altered secretome profile, including vascular endothelial growth factor, Angiopoietin-1 and -2 factors. In addition to anti-angiogenic properties of conferone, a profound decrease in migration capability of HT-29 cells was also evident.
authors.affiliation: Department of Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.
authors.forename: Omid
authors.initials: O
authors.lastname: Cheraghi
authors.affiliation: Department of Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.. Electronic address: dehghan2001d@yahoo.com.
authors.forename: Gholamreza
authors.initials: G
authors.lastname: Dehghan
authors.affiliation: Department of Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.
authors.forename: Majid
authors.initials: M
authors.lastname: Mahdavi
authors.affiliation: Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Reza
authors.initials: R
authors.lastname: Rahbarghazi
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Aysa
authors.initials: A
authors.lastname: Rezabakhsh
authors.affiliation: Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Hojjatollah Nozad
authors.initials: HN
authors.lastname: Charoudeh
authors.affiliation: Biotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Iranshahi
authors.affiliation: Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran; Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Soheila
authors.initials: S
authors.lastname: Montazersaheb
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D042683:Angiopoietin-1 / Q000378:metabolism; D042682:Angiopoietins / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002374:Catalase / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D003374:Coumarins / Q000494:pharmacology* / Q000627:therapeutic use; D005309:Ferula / Q000737:chemistry*; D019073:HT29 Cells; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C467630:ANGPT1 protein, human; D020533:Angiogenesis Inhibitors; D042683:Angiopoietin-1; D042682:Angiopoietins; D000972:Antineoplastic Agents, Phytogenic; D003374:Coumarins; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D042461:Vascular Endothelial Growth Factor A; C513235:conferone; D002374:Catalase; D013482:Superoxide Dismutase
keywords: Angiopoietin-1; Colorectal adenocarcinoma; Conferone; P-glycoprotein; Reactive oxygen species