title: HA-1077 inhibits cell migration/invasion of oral squamous cell carcinoma.
abstract: Oral squamous cell carcinoma (OSCC) is the most malignant lesion occurring in the head and neck. The Rho-kinases (ROCKs), effectors of Rho proteins, are involved in actin cytoskeletal organization, cell migration, and maintenance cortex. The HA-1077 inhibits the ROCKs. This study aimed to evaluate the effect of treatment with HA-1077 on cell motility in SCC-4 cells, a cell line originating from human OSCC. F-actin of SCC-4 cells treated or not with HA-1077 (1, 50 and 100 μmol/l), and also HA-1077 50 μmol/l and/or inhibitors Y-27632 30 μmol/l was stained with rhodamine-conjugated phalloidin and analyzed by confocal microscopy. Approximately 1×10 cells/well, control and treated with HA-1077 (25, 50, and 100 μmol/l) were added to the migration plate assay. In addition, 1×10 cells/well, control and treated with HA-1077 50 μmol/l, were tested by invasion assays (plate coated with Matrigel). The inhibition of ROCKs with HA-1077 and/or Y-27632 leads to morphological changes, affecting the organization of the actin. The inhibitory effect of HA-1077 (P<0.0001) was dose dependent as the number of cells migrated at 100 μmol/l was statistically different: 25 μmol/l (P<0.0001) and 50 μmol/l (P<0.01). The number of cells treated with HA-1077 50 μmol/l decreased compared with control cells that invaded through Matrigel (P<0.0001). This study shows an inhibitory effect of HA-1077 on cell migration and invasion, suggesting that the use of HA-1077 can be a potential therapy for OSCC.
authors.affiliation: Departments of aStructural Biology bPharmacology, Institute of Natural and Biological Sciences, Federal University of Triângulo Mineiro, Uberaba, MG, Brazil.
authors.forename: Simone de Sales Costa
authors.initials: Sde S
authors.lastname: Moreira Carboni
authors.forename: Nathália Alves
authors.initials: NA
authors.lastname: Rodrigues Lima
authors.forename: Nanci Mendes
authors.initials: NM
authors.lastname: Pinheiro
authors.forename: Beatriz Martins
authors.initials: BM
authors.lastname: Tavares-Murta
authors.forename: Virgínia Oliveira
authors.initials: VO
authors.lastname: Crema
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008841:Actin Cytoskeleton / Q000187:drug effects / Q000648:ultrastructure; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D045744:Cell Line, Tumor / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D006801:Humans; D009062:Mouth Neoplasms / Q000473:pathology*; D009361:Neoplasm Invasiveness; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D054460:rho-Associated Kinases; C049347:fasudil