title: 4-Amino-2-trifluoromethyl-phenyl retinate inhibits the migration of BGC-823 human gastric cancer cells by downregulating the phosphorylation level of MLC II.
abstract: 4-Amino-2-trifluoromethyl-phenyl retinate (ATPR) is a novel all-trans retinoic acid (ATRA) derivative which was reported to have a superior antitumor effect in breast cancer cells. However, little is known about its antitumor effects on human gastric cancer cells and the mechanisms have not been fully elucidated. The results of the present study suggest that in the human gastric carcinoma cell line BGC-823, ATPR plays a more effective role than ATRA at the same dose in inhibiting proliferation, migration and inducing differentiation after the same treatment time. Furthermore, we investigated the preliminary mechanism of ATPR's anti‑migration effect. Immunofluorescence assay demonstrated that claudin-18 positioned from cytoplasm to cell surface following ATPR stimuli. Real-time quantitative RT-PCR and western blot analyses showed that ATPR had significant effects on downregulation of the phosphorylation level of myosin light chain II (MLC II) by suppressing myosin light chain kinase (MLCK) and Rho-associated coiled-coil containing kinase (ROCK), as well as its regulation in the protein expression of RARα and RARβ. Moreover, ATPR increased the activity of myosin phosphatase by inhibiting ROCK. Consequently, ATPR showed more promising antitumor effects than ATRA in BGC-823 in vitro, and it may conduct its anti-migration effects by decreasing the phosphorylation level of MLC II, as well as by regulating MLCK and ROCK as downstream target genes.
authors: Institute of Clinical Pharmacology, Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors: Anla
authors: A
authors: Hu
authors: Laboratory of Molecular Biology and Department of Biochemistry, Key Laboratory of Anti-Inflammatory and Immunological Pharmacology, Ministry of Education and Key Laboratory of Gene Resource Utilization for Severe Disease of Anhui Province, Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors: Yanyan
authors: Y
authors: Yang
authors: Laboratory of Molecular Biology and Department of Biochemistry, Key Laboratory of Anti-Inflammatory and Immunological Pharmacology, Ministry of Education and Key Laboratory of Gene Resource Utilization for Severe Disease of Anhui Province, Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors: Sumei
authors: S
authors: Zhang
authors: Laboratory of Molecular Biology and Department of Biochemistry, Key Laboratory of Anti-Inflammatory and Immunological Pharmacology, Ministry of Education and Key Laboratory of Gene Resource Utilization for Severe Disease of Anhui Province, Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors: Qing
authors: Q
authors: Zhou
authors: Institute of Clinical Pharmacology, Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors: Wei
authors: W
authors: Wei
authors: Institute of Clinical Pharmacology, Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors: Yuan
authors: Y
authors: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D024722:Cardiac Myosins / Q000187:drug effects* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D015536:Down-Regulation; D006801:Humans; D018994:Myosin Light Chains / Q000187:drug effects* / Q000378:metabolism; D009219:Myosin-Light-Chain Kinase / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D018168:Receptors, Retinoic Acid / Q000187:drug effects / Q000378:metabolism; D000072482:Retinoic Acid Receptor alpha; D012176:Retinoids / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000378:metabolism*; D054460:rho-Associated Kinases / Q000187:drug effects / Q000378:metabolism
chemical_list: C585745:4-amino-2-trifluoromethyl-phenyl retinate; D000970:Antineoplastic Agents; D018994:Myosin Light Chains; C000607071:RARA protein, human; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D012176:Retinoids; C107184:myosin light chain 2; C082925:retinoic acid receptor beta; D054460:rho-Associated Kinases; D009219:Myosin-Light-Chain Kinase; D024722:Cardiac Myosins