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Molecular Targets for Therapy (MTT)

Hyperforin inhibits MMP-9 secretion by B-CLL cells and microtubule formation by endothelial cells

Abstract

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.

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Acknowledgements

This work was supported by INSERM, Canceropôle Ile-de-France and by a grant from ARC (#3322). CQ was supported by a grant of the Société Française d'Hématologie. We thank the clinicians of the Department of Hematology of the Hôtel-Dieu hospital, and Mrs S Pasco-Dubrulle for technical assistance.

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Correspondence to J-P Kolb.

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Quiney, C., Billard, C., Mirshahi, P. et al. Hyperforin inhibits MMP-9 secretion by B-CLL cells and microtubule formation by endothelial cells. Leukemia 20, 583–589 (2006). https://doi.org/10.1038/sj.leu.2404134

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  • DOI: https://doi.org/10.1038/sj.leu.2404134

Keywords

  • hyperforin
  • B-CLL
  • MMP-9
  • VEGF
  • angiogenesis
  • endothelial cells

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