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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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Matrix metalloprotease production by HT1080 cells analysed by gelatin zymography of the conditioned medium. The 59 and 120 kDa forms were present as traces.
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fig4: Matrix metalloprotease production by HT1080 cells analysed by gelatin zymography of the conditioned medium. The 59 and 120 kDa forms were present as traces.

Mentions: To further gain insights into the characterisation of the selected coumarin derivatives tested (4 and 7), we have evaluated their activity against serine proteases and MMPs released by HT1080 cells. We first performed plasminogen and gelatin zymographic analysis on HT1080 cell conditioned media. Plasminogen activator activity was detected in all samples. Densitometric analysis of zymograms revealed greater amounts of HMW-uPA than LMW-uPA. Gelatin zymography demonstrated the presence of pro-MMP-2 (66 kDa), pro-MMP-9 (92 kDa), two MMP-2 activated forms (62 and 59 kDa) and a 120 kDa gelatinolytic species (Figure 4Figure 4


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)

Matrix metalloprotease production by HT1080 cells analysed by gelatin zymography of the conditioned medium. The 59 and 120 kDa forms were present as traces.
© Copyright Policy
Related In: Results  -  Collection

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

fig4: Matrix metalloprotease production by HT1080 cells analysed by gelatin zymography of the conditioned medium. The 59 and 120 kDa forms were present as traces.
Mentions: To further gain insights into the characterisation of the selected coumarin derivatives tested (4 and 7), we have evaluated their activity against serine proteases and MMPs released by HT1080 cells. We first performed plasminogen and gelatin zymographic analysis on HT1080 cell conditioned media. Plasminogen activator activity was detected in all samples. Densitometric analysis of zymograms revealed greater amounts of HMW-uPA than LMW-uPA. Gelatin zymography demonstrated the presence of pro-MMP-2 (66 kDa), pro-MMP-9 (92 kDa), two MMP-2 activated forms (62 and 59 kDa) and a 120 kDa gelatinolytic species (Figure 4Figure 4

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