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Antitumor effect of valorphin in vitro and in vivo: combined action with cytostatic drugs.

Abstract
The action of the cytostatic drugs (epirubicin and vincristine) in combination with the endogenous antiproliferative beta-hemoglobin fragment (33-39), valorphin, was studied in tumor (L929 and A549) cell cultures, primary culture of murine bone marrow cells and in murine model of breast carcinoma in vivo. Simultaneous application of 1 microM valorphin and 1 microM epirubicin, in vitro, did not result in an additive suppressive effect on cell culture growth. Additive effects were achieved with alternating applications of the peptide and the drugs, namely, 0.5 microM (but not 1 microM) epirubicin added 24 h prior to 1 microM valorphin; 1 microM valorphin added 48 h prior to 0.1 microM epirubicin, or 0.1 microM vincristine, or 0.05 microM vincristine, which resulted in 100% cell death in the both series with vincristine and up to 78% cell biomass reduction in the experiments with epirubicin. In the in vivo model (female BLRB mice with subcutaneously inoculated syngeneic mammary carcinoma), simultaneous treatment with 25 mg/m(2) epirubicin and 1 mg/kg valorphin resulted in 42% of tumor growth inhibition, as compared with the negative control group and 22% inhibition as compared with the epirubcin-treated group (at 20th day of treatment). Survival was significantly improved (69% compared to 39% in the group treated with epirubicin only) at day 26 after the treatment beginning.
AuthorsElena Yu Blishchenko, Olga V Sazonova, Olga A Kalinina, Ekaterina V Moiseeva, Arpad A Vass, Andrey A Karelin, Vadim T Ivanov
JournalCancer biology & therapy (Cancer Biol Ther) Vol. 4 Issue 1 Pg. 118-24 (Jan 2005) ISSN: 1538-4047 [Print] United States
PMID15662114 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibiotics, Antineoplastic
  • Antineoplastic Agents, Phytogenic
  • Epirubicin
  • Vincristine
  • valorphin
  • Adamantane
Topics
  • Adamantane (analogs & derivatives, pharmacology)
  • Animals
  • Antibiotics, Antineoplastic (pharmacology)
  • Antineoplastic Agents, Phytogenic (pharmacology)
  • Bone Marrow Cells
  • Breast Neoplasms (pathology, veterinary)
  • Carcinoma (pathology, veterinary)
  • Cell Proliferation (drug effects)
  • Drug Interactions
  • Epirubicin (pharmacology)
  • Fibroblasts
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Survival
  • Tumor Cells, Cultured
  • Vincristine (pharmacology)

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