title: A novel all-trans retinoid acid derivatives inhibits the migration of breast cancer cell lines MDA-MB-231 via myosin light chain kinase involving p38-MAPK pathway.
abstract: OBJECTIVE
  To explore the effect and its probable mechanism of a synthetic retinoid 4-amino-2-tri-fluoromethyl-phenyl ester (ATPR) on the migration of human breast cancer MDA-MB-231 cells.
  
  
  METHODS
  MTT assay was performed to measure the proliferation of MDA-MB-231 cells treated with different concentrations of all-trans retinoic acid (ATRA) and ATPR. The effect of ATPR and ML-7, a selective inhibitor of myosin light chain kinase (MLCK), and SB203580, an inhibitor of p38, on the migration of MDA-MB-231 cells were analyzed by wound healing assay. The expression of MLCK and phosphorylation of myosin light chain (MLC), ERK, JNK, p38 proteins were detected by western blot
  
  
  RESULTS
  After the cells were treated by ATRA and ATPR, the proliferation and migration of breast cancer MDA-MB-231 cells were inhibited significantly. The IC 50 of ATRA and ATPR is 34.08 μmol/l and 18.06 μmol/l respectively. The relative migration rate of MDA-MB-231 cells treated with ATPR reached 50% at 48 h while the ATRA group is over 90%. The relative migration rate of ML-7 group and SB group had significant decrease compared with control group. The expression level of MLCK and phosphorylation of MLC of breast cancer cells was reduced when the cells were treated by ATPR with 48 h, the phosphorylation of ERK, JNK and p38 in breast cancer also reduced when cells were treated by ATPR with 2 h. In addition, ML-7 (50 μmol/l) could inhibit the phosphorylation of p38 and SB (50 μmol/l) could inhibit the expression of MLCK and phosphorylation of MLC.
  
  
  CONCLUSIONS
  ATPR had a better inhibition on the proliferation and the migration of breast cancer MDA-MB-231 cells than ATRA, and its probable mechanism was associated with the down regulation of expression of MLCK and phosphorylation of MLC protein involving p38-MAPK pathway.
authors.affiliation: Laboratory of Molecular Biology and Department of Biochemistry, Anhui Medical University, Hefei, 230032 Anhui, PR China.
authors.forename: Bei
authors.initials: B
authors.lastname: Wang
authors.forename: Yunwen
authors.initials: Y
authors.lastname: Yan
authors.forename: Jiali
authors.initials: J
authors.lastname: Zhou
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhou
authors.forename: Shuyu
authors.initials: S
authors.lastname: Gui
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001381:Azepines / Q000494:pharmacology; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism; D009281:Naphthalenes / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D012176:Retinoids / Q000008:administration & dosage / Q000494:pharmacology*; D014212:Tretinoin / Q000008:administration & dosage / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: C585745:4-amino-2-trifluoromethyl-phenyl retinate; D000970:Antineoplastic Agents; D001381:Azepines; D007093:Imidazoles; D009281:Naphthalenes; D011725:Pyridines; D012176:Retinoids; C070571:ML 7; D014212:Tretinoin; D009219:Myosin-Light-Chain Kinase; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580