Tetra-amidines exhibiting anti-proteinase activity: effects on oriented migration and in vitro invasiveness of a Chinese hamster cell line transfected with the activated human T24-Ha-ras-1 oncogene.
In the present paper we have investigated the effects of aromatic tetra-amidines on attachment, oriented migration and in vitro invasiveness of the Chinese Hamster FH06T1-1 fibroblast lung cell line, transformed with the activated human T24-Ha-ras-1 oncogene. The FH06T1-1 cell line is tumorigenic in nude mice and displays growth properties and biological features clearly distinct from those of the FH06N1-1 cell line, obtained after transfection of the same fibroblast cells with the normal Ha-ras-1 proto-oncogene. Attachment, oriented migration and invasiveness were analysed by culturing the cells on a reconstituted extracellular matrix, composed of collagen IV, laminin, entactin and heparan sulphate proteoglycans. The results obtained demonstrate that oriented migration is performed only by FH06T1-1 cells and that tetra-benzamidines are effective inhibitors of oriented migration and "in vitro" invasiveness of these tumorigenic cells. These findings should encourage further studies on the possible antimetastatic effects of these antiproteinase tetra-benzamidines on experimental animals.
Dip. di Scienze Farmaceutiche, Universita di Ferrara, Italy.
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C
Nastruzzi
R
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Barbieri
R
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Ferroni
M
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Guarneri
D
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Spandidos
R
R
Gambari
D000578:Amidines / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents; D001550:Benzamidines / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D006224:Cricetinae; D003412:Cricetulus; D003864:Depression, Chemical; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D011905:Genes, ras / Q000187:drug effects; D006801:Humans; D009361:Neoplasm Invasiveness; D015689:Oncogene Protein p21(ras) / Q000096:biosynthesis; D011480:Protease Inhibitors; D000090063:Proto-Oncogene Mas; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D000578:Amidines; D000970:Antineoplastic Agents; D001550:Benzamidines; C000715470:MAS1 protein, human; D011480:Protease Inhibitors; D000090063:Proto-Oncogene Mas; C057886:4,4'-(2,2-bis((4-(aminoiminomethyl)-2-bromophenoxy)methyl)-1,3-propanediyl)bis(oxy))bis(3-bromobenzenecarboximidamide; D015689:Oncogene Protein p21(ras)