Hyperforin inhibits MMP-9 secretion by B-CLL cells and microtubule formation by endothelial cells.
We previously reported that hyperforin (HF), a natural phloroglucinol purified from Saint John's wort, can induce the apoptosis of leukemic cells from patients with B-cell lymphocytic leukemia (B-CLL) ex vivo. We show here that treatment of cultured B-CLL patients' cells with HF results in a marked inhibition of their capacity to secrete matrix metalloproteinase-9, an essential component in neo-angiogenesis through degradation of the extracellular matrix process. The phloroglucinol acts by decreasing the production of the latent 92 kDa pro-enzyme. The inhibitory effect of HF is associated with a decrease in VEGF release by the leukemic cells. Moreover, HF is found to prevent the formation of microtubules by human bone marrow endothelial cells cultured on Matrigel, evidencing its capacity to inhibit vessel formation. Our results show the antiangiogenesis activity of HF and strengthen its potential interest in the therapy of B-CLL.
UMRS 736 INSERM and Université Pierre et Marie Curie-Paris 6, Centre de Recherches Biomédicales des Cordeliers, Paris, France.
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Quiney
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Billard
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Mirshahi
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Fourneron
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JP
Kolb
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000187:drug effects*; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D004354:Drug Screening Assays, Antitumor; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D018093:Gelatinases / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D015448:Leukemia, B-Cell / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism*; D008875:Middle Aged; D010696:Phloroglucinol / Q000031:analogs & derivatives* / Q000494:pharmacology; D013729:Terpenes / Q000494:pharmacology*; D042442:Vascular Endothelial Growth Factors / Q000037:antagonists & inhibitors
D001643:Bridged Bicyclo Compounds; D061965:Matrix Metalloproteinase Inhibitors; D013729:Terpenes; D042442:Vascular Endothelial Growth Factors; D010696:Phloroglucinol; D018093:Gelatinases; D020780:Matrix Metalloproteinase 9; C001654:hyperforin