title: Retinol inhibits the invasion of retinoic acid-resistant colon cancer cells in vitro and decreases matrix metalloproteinase mRNA, protein, and activity levels.
abstract: Retinol inhibits the growth of all-trans-retinoic acid (ATRA)-resistant human colon cancer cell lines through a retinoic acid receptor (RAR)-independent mechanism. The objectives of the current study were to determine if retinol inhibited the invasion of ATRA-resistant colon cancer cells independent of RAR and the effects of retinol on matrix metalloproteinases (MMPs). Retinol inhibited the migration and invasion of two ATRA-resistant colon cancer cell lines, HCT-116 and SW620, in a dose-dependent manner. To determine if transcription, particularly RAR-mediated transcription, or translation of new genes was required for retinol to inhibit cell invasion, cells were treated with retinol and cycloheximide, actinomycin D, or an RAR pan-antagonist. Treatment of cells with retinol and cycloheximide, actinomycin D, or an RAR pan-antagonist did not block the ability of retinol to inhibit cell invasion. In addition, retinol decreased MMP-1 mRNA levels in both cell lines, MMP-2 mRNA levels in the SW620 cell line, and MMP-7 and -9 mRNA levels in the HCT-116 cell line. Retinol also decreased the activity of MMP-2 and -9 and MMP-9 protein levels while increasing tissue inhibitor of MMP-1 media levels. In conclusion, retinol reduces the metastatic potential of ATRA-resistant colon cancer cells via a novel RAR-independent mechanism that may involve decreased MMP mRNA levels and activity.
authors.affiliation: Department of Human Ecology, Institute of Cellular and Molecular Biology, The University of Texas at Austin 78712, USA.
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Park
authors.forename: Erik T
authors.initials: ET
authors.lastname: Wilder
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Lane
mesh_terms: D000970:Antineoplastic Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D045325:HCT116 Cells; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D014212:Tretinoin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014801:Vitamin A / Q000037:antagonists & inhibitors / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D014801:Vitamin A; D014212:Tretinoin; D020782:Matrix Metalloproteinases