4-Hydroxycoumarin disorganizes the actin cytoskeleton in B16-F10 melanoma cells but not in B82 fibroblasts, decreasing their adhesion to extracellular matrix proteins and motility.
This study determined the in vitro effects of 4-hydroxycoumarin (4-HC) employing the melanoma cell line B16-F10 and the non-malignant fibroblastic cell line B82. 4-HC disorganized the actin cytoskeleton in B16-F10 cells, but not in B82 fibroblasts. Cytoskeletal disorganization correlated with reductions in cell adhesion to four extracellular matrix proteins and inhibition of random motility. 4-HC did not modify cell viability or actin expression, but decreased tyrosine phosphorylation of several proteins in melanoma cells. Because adhesion of tumor cells to extracellular matrix is required during the metastatic process, 4-HC might be useful as an adjuvant therapy for melanoma.
Velasco-Velázquez
Marco Antonio
MA
Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, Apdo. Postal 70-297, Ciudad Universitaria, México, DF 04510, Mexico. marcovelasco@correo.unam.mx
Agramonte-Hevia
José
J
Barrera
Diana
D
Jiménez-Orozco
Alejandro
A
García-Mondragón
María Juana
MJ
Mendoza-Patiño
Nicandro
N
Landa
Abraham
A
Mandoki
Juan
J
D015110:4-Hydroxycoumarins / Q000494:pharmacology*; D000199:Actins / Q000187:drug effects*; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects* / Q000648:ultrastructure; D016326:Extracellular Matrix Proteins / Q000187:drug effects / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D008546:Melanoma, Experimental / Q000503:physiopathology; D051379:Mice; D009363:Neoplasm Proteins / Q000187:drug effects / Q000378:metabolism; D019000:Phosphotyrosine / Q000378:metabolism; D014407:Tumor Cells, Cultured
D015110:4-Hydroxycoumarins; D000199:Actins; D016326:Extracellular Matrix Proteins; D009363:Neoplasm Proteins; D019000:Phosphotyrosine; C068805:4-hydroxycoumarin