3-Bromophenyl 6-acetoxymethyl-2-oxo-2H-1-benzopyran-3-carboxylate inhibits cancer cell invasion in vitro and tumour growth in vivo.
In search for new anticancer agents, we have evaluated the antiinvasive and antimigrative properties of recently developed synthetic coumarin derivatives among which two compounds revealed important activity: 3-chlorophenyl 6-acetoxymethyl-2-oxo-2H-1-benzopyran-3-carboxylate and 3-bromophenyl 6-acetoxymethyl-2-oxo-2H-1-benzopyran-3-carboxylate. Both drugs were able to inhibit cell invasion markedly in a Boyden chamber assay, the bromo derivative being more potent than the reference matrix metalloprotease (MMP) inhibitor GI 129471. In vivo, tumour growth was reduced when nude mice grafted with HT1080 or MDA-MB231 cells were treated i.p. 3 days week(-1) with the bromo coumarin derivative. These effects were not associated with the inhibition of urokinase, plasmin, MMP-2 or MMP-9. The mechanism of action of the drugs remains to be elucidated. However, these two coumarin derivatives may serve as new lead compounds of an original class of antitumour agents.
Kempen
I
I
Centre Interfacultaire de Recherche en Pharmacochimie des substances naturelles et synthétiques, Laboratoire de Chimie Pharmaceutique, Université de Liège, Belgique. I.Kempen@ulg.ac.be
Papapostolou
D
D
Thierry
N
N
Pochet
L
L
Counerotte
S
S
Masereel
B
B
Foidart
J-M
JM
Reboud-Ravaux
M
M
Noël
A
A
Pirotte
B
B
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001578:Benzopyrans / Q000494:pharmacology*; D002264:Carboxylic Acids / Q000494:pharmacology*; D003374:Coumarins / Q000494:pharmacology*; D005260:Female; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D051379:Mice; D009361:Neoplasm Invasiveness; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
C474005:3-bromophenyl-6-acetoxymethyl-2-oxo-2H-1-benzopyran-3-carboxylate; D000970:Antineoplastic Agents; D001578:Benzopyrans; D002264:Carboxylic Acids; D003374:Coumarins; D014568:Urokinase-Type Plasminogen Activator; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9