The tetrapeptide acetyl-N-Ser-Asp-Lys-Pro (Goralatide) protects from doxorubicin-induced toxicity: improvement in mice survival and protection of bone marrow stem cells and progenitors. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Blood Année : 1998

The tetrapeptide acetyl-N-Ser-Asp-Lys-Pro (Goralatide) protects from doxorubicin-induced toxicity: improvement in mice survival and protection of bone marrow stem cells and progenitors.

A. Massé
  • Fonction : Auteur
L. Ramirez
  • Fonction : Auteur
G Bindoula
  • Fonction : Auteur
K Raddassi
  • Fonction : Auteur
P Deschamps de Paillette
  • Fonction : Auteur
J Mencia-Huerta
  • Fonction : Auteur
S. Koscielny
  • Fonction : Auteur
P. Potier
  • Fonction : Auteur
F Sainteny
  • Fonction : Auteur
P. Carde
  • Fonction : Auteur

Résumé

The tetrapeptide Acetyl-N-Ser-Asp-Lys-Pro (AcSDKP or Goralatide), a physiological regulator of hematopoiesis, inhibits the entry into the S-phase of murine and human hematopoietic stem cells. It has been shown to reduce the damage to specific compartments in the bone marrow resulting from treatment with chemotherapeutic agents, ionizing radiations, hyperthermy, or phototherapy. The present study was performed to assess the therapeutic potential of AcSDKP in vivo in reducing both the toxicity and the hematopoietic damage induced by fractionated administration of doxorubicin (DOX), a widely used anticancer drug. Here we showed that AcSDKP could reduce DOX-induced mortality in mice and could protect particularly the long-term reconstituting cells (LTRCs) in addition to colony forming units-spleen, high proliferative potential colony-forming cells, and colony-forming units-granulocyte-macrophage (CFU-GM) from DOX toxicity. The protection against DOX-induced mortality in mice was improved when AcSDKP was administered for 3 days, at a dose of 2.4 micrograms/d, by continuous subcutaneous (SC) infusion or fractionated s.c. injections starting 48 hours before DOX treatment. Moreover, the recovery of the CFU-GM population in the AcSDKP-DOX-treated mice was optimized by the subsequent administration of granulocyte colony-stimulating factor (G-CSF). The coadministration of AcSDKP with DOX may improve its therapeutic index by reducing both acute hematotoxicity on late stem cells and progenitors and long-term toxicity on LTRCs. Optimization of these treatments combined with G-CSF may provide an additional approach to facilitate hematopoietic recovery after cancer chemotherapy.
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Dates et versions

hal-02114623 , version 1 (29-04-2019)

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  • HAL Id : hal-02114623 , version 1
  • PUBMED : 9427696

Citer

A. Massé, L. Ramirez, G Bindoula, Catherine Grillon, J. Wdzieczak-Bakala, et al.. The tetrapeptide acetyl-N-Ser-Asp-Lys-Pro (Goralatide) protects from doxorubicin-induced toxicity: improvement in mice survival and protection of bone marrow stem cells and progenitors.. Blood, 1998, 91 (2), pp.441-9. ⟨hal-02114623⟩
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