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3-Bromophenyl 6-acetoxymethyl-2-oxo-2H-1-benzopyran-3-carboxylate inhibits cancer cell invasion in vitro and tumour growth in vivo.

Kempen I, Papapostolou D, Thierry N, Pochet L, Counerotte S, Masereel B, Foidart JM, Reboud-Ravaux M, Noël A, Pirotte B - Br. J. Cancer (2003)

Bottom Line: 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.However, these two coumarin derivatives may serve as new lead compounds of an original class of antitumour agents.

View Article: PubMed Central - PubMed

Affiliation: Centre Interfacultaire de Recherche en Pharmacochimie des substances naturelles et synthétiques, Laboratoire de Chimie Pharmaceutique, Université de Liège, Belgique. I.Kempen@ulg.ac.be

ABSTRACT
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.

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Related in: MedlinePlus

Synthetic coumarin derivatives reduce HT1080 fibrosarcoma cells invasion. HT1080 chemoinvasion was evaluated in Transwell cell culture inserts coated with type IV collagen. HT1080 cells (6 × 104) were seeded in the absence (control) or presence of different concentrations of coumarinic inhibitor (0.1, 1 and 10 μM) and the number of cells that have migrated was determined by visually counting the number of cells present on the lower side of the filters, as described in Materials and Methods: (A) 3-chlorophenyl 2-oxo-2H-1-benzopyran-3-carboxylate derivatives diversally substituted in the 6-position and (B) 6-acetoxymethyl-2-oxo-2H-1-benzopyran-3-carboxylic acid derivatives.
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fig2: Synthetic coumarin derivatives reduce HT1080 fibrosarcoma cells invasion. HT1080 chemoinvasion was evaluated in Transwell cell culture inserts coated with type IV collagen. HT1080 cells (6 × 104) were seeded in the absence (control) or presence of different concentrations of coumarinic inhibitor (0.1, 1 and 10 μM) and the number of cells that have migrated was determined by visually counting the number of cells present on the lower side of the filters, as described in Materials and Methods: (A) 3-chlorophenyl 2-oxo-2H-1-benzopyran-3-carboxylate derivatives diversally substituted in the 6-position and (B) 6-acetoxymethyl-2-oxo-2H-1-benzopyran-3-carboxylic acid derivatives.

Mentions: To determine whether coumarin derivatives could reduce the invasive behaviour of tumour cells, we measured the ability of cells treated or not with the coumarin derivative to pass through type IV collagen-coated Transwell cell culture inserts (chemoinvasion assay). Cell invasion in the absence of coumarin derivative was considered as 100% (Figure 2A and BFigure 2


3-Bromophenyl 6-acetoxymethyl-2-oxo-2H-1-benzopyran-3-carboxylate inhibits cancer cell invasion in vitro and tumour growth in vivo.

Kempen I, Papapostolou D, Thierry N, Pochet L, Counerotte S, Masereel B, Foidart JM, Reboud-Ravaux M, Noël A, Pirotte B - Br. J. Cancer (2003)

Synthetic coumarin derivatives reduce HT1080 fibrosarcoma cells invasion. HT1080 chemoinvasion was evaluated in Transwell cell culture inserts coated with type IV collagen. HT1080 cells (6 × 104) were seeded in the absence (control) or presence of different concentrations of coumarinic inhibitor (0.1, 1 and 10 μM) and the number of cells that have migrated was determined by visually counting the number of cells present on the lower side of the filters, as described in Materials and Methods: (A) 3-chlorophenyl 2-oxo-2H-1-benzopyran-3-carboxylate derivatives diversally substituted in the 6-position and (B) 6-acetoxymethyl-2-oxo-2H-1-benzopyran-3-carboxylic acid derivatives.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2376372&req=5

fig2: Synthetic coumarin derivatives reduce HT1080 fibrosarcoma cells invasion. HT1080 chemoinvasion was evaluated in Transwell cell culture inserts coated with type IV collagen. HT1080 cells (6 × 104) were seeded in the absence (control) or presence of different concentrations of coumarinic inhibitor (0.1, 1 and 10 μM) and the number of cells that have migrated was determined by visually counting the number of cells present on the lower side of the filters, as described in Materials and Methods: (A) 3-chlorophenyl 2-oxo-2H-1-benzopyran-3-carboxylate derivatives diversally substituted in the 6-position and (B) 6-acetoxymethyl-2-oxo-2H-1-benzopyran-3-carboxylic acid derivatives.
Mentions: To determine whether coumarin derivatives could reduce the invasive behaviour of tumour cells, we measured the ability of cells treated or not with the coumarin derivative to pass through type IV collagen-coated Transwell cell culture inserts (chemoinvasion assay). Cell invasion in the absence of coumarin derivative was considered as 100% (Figure 2A and BFigure 2

Bottom Line: 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.However, these two coumarin derivatives may serve as new lead compounds of an original class of antitumour agents.

View Article: PubMed Central - PubMed

Affiliation: Centre Interfacultaire de Recherche en Pharmacochimie des substances naturelles et synthétiques, Laboratoire de Chimie Pharmaceutique, Université de Liège, Belgique. I.Kempen@ulg.ac.be

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus