title: Imazamethabenz inhibits human breast cancer cell proliferation, migration and invasion via combination with Pin1.
abstract: Overexpression of peptidyl-prolyl cis/trans isomerase, NIMA interacting‑1 (Pin1) is a significant marker of the occurrence and development of tumors. In the present study, the imidazoline ketone herbicide imazamethabenz was investigated as a potential antitumor drug by inhibiting Pin1. Molecular docking and enzyme activity tests verified, for the first time, that the imidazoline ketone compound imazamethabenz effectively inhibited Pin1 in vitro. MTT assays, western blotting, wound healing assay and Matrigel invasion assays revealed that imazamethabenz induced apoptosis and inhibited migration and invasion of the breast cancer cell line MCF‑7, which overexpresses Pin1, by inhibiting the Pin1‑mediated signaling pathway involving vascular endothelial growth factor and matrix metalloproteinase 9. These findings indicated that imazamethabenz offers potential applications for the treatment of tumors as a Pin1 inhibitor.
authors.affiliation: College of Pharmacy, Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Chen
authors.initials: C
authors.lastname: Liu
authors.affiliation: College of Pharmacy, Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Chaoyu
authors.initials: C
authors.lastname: Mu
authors.affiliation: College of Pharmacy, Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Zeng
authors.initials: Z
authors.lastname: Li
authors.affiliation: College of Pharmacy, Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Xu
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001665:Binding Sites; D001943:Breast Neoplasms; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006801:Humans; D006860:Hydrogen Bonding; D048288:Imidazolines / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D061986:MCF-7 Cells; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D062105:Molecular Docking Simulation; D000072340:NIMA-Interacting Peptidylprolyl Isomerase / Q000037:antagonists & inhibitors / Q000378:metabolism; D017434:Protein Structure, Tertiary; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D048288:Imidazolines; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D042461:Vascular Endothelial Growth Factor A; D020780:Matrix Metalloproteinase 9; C000606846:PIN1 protein, human