Retinol inhibits the invasion of retinoic acid-resistant colon cancer cells in vitro and decreases matrix metalloproteinase mRNA, protein, and activity levels.
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.
Park
Eun Young
EY
Department of Human Ecology, Institute of Cellular and Molecular Biology, The University of Texas at Austin 78712, USA.
Wilder
Erik T
ET
Lane
Michelle A
MA
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*
D000970:Antineoplastic Agents; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D014801:Vitamin A; D014212:Tretinoin; D020782:Matrix Metalloproteinases