Omid Cheraghi1, Gholamreza Dehghan2, Majid Mahdavi1, Reza Rahbarghazi3, Aysa Rezabakhsh4, Hojjatollah Nozad Charoudeh3, Mehrdad Iranshahi5, Soheila Montazersaheb6. 1. Department of Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran. 2. Department of Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.. Electronic address: dehghan2001d@yahoo.com. 3. Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. 4. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran. 5. Biotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. 6. 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.
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.
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.