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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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(A) Incidence of tumours induced by subcutaneous (s.c.) injection of HT1080 cells (percent of animals bearing tumour higher than 80 mm3). (B) Growth curves of tumour formed, in nude mice (n=6), after s.c. injection of HT1080 cells (1 × 106) mixed with matrigel. The mice were examined twice a week for tumour appearance and measurement.
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fig5: (A) Incidence of tumours induced by subcutaneous (s.c.) injection of HT1080 cells (percent of animals bearing tumour higher than 80 mm3). (B) Growth curves of tumour formed, in nude mice (n=6), after s.c. injection of HT1080 cells (1 × 106) mixed with matrigel. The mice were examined twice a week for tumour appearance and measurement.

Mentions: We next investigated the influence of the two selected compounds 4 and 7 (Y=CH2OCOCH3; X′=Cl and Br) on the development of tumours induced by the injection into nude mice of human breast adenocarcinoma and fibrosarcoma cells. Treatment of mice with bromo derivative (compound 7) was found to reduce both the incidence (log Rank test, P<0.004) and growth of tumours induced by sc injection of HT1080 cells (Figure 5A and BFigure 5


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)

(A) Incidence of tumours induced by subcutaneous (s.c.) injection of HT1080 cells (percent of animals bearing tumour higher than 80 mm3). (B) Growth curves of tumour formed, in nude mice (n=6), after s.c. injection of HT1080 cells (1 × 106) mixed with matrigel. The mice were examined twice a week for tumour appearance and measurement.
© Copyright Policy
Related In: Results  -  Collection

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

fig5: (A) Incidence of tumours induced by subcutaneous (s.c.) injection of HT1080 cells (percent of animals bearing tumour higher than 80 mm3). (B) Growth curves of tumour formed, in nude mice (n=6), after s.c. injection of HT1080 cells (1 × 106) mixed with matrigel. The mice were examined twice a week for tumour appearance and measurement.
Mentions: We next investigated the influence of the two selected compounds 4 and 7 (Y=CH2OCOCH3; X′=Cl and Br) on the development of tumours induced by the injection into nude mice of human breast adenocarcinoma and fibrosarcoma cells. Treatment of mice with bromo derivative (compound 7) was found to reduce both the incidence (log Rank test, P<0.004) and growth of tumours induced by sc injection of HT1080 cells (Figure 5A and BFigure 5

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