Effect of Buthionine Sulfoximine on the Sensitivity to Doxorubicin of Parent and MDR Tumor Cell Lines
Autor: | A. Flugy, Marilena Crescimanno, Flandina C, Nicolò Borsellino, V. Leonardi, Luciano Rausa, N D'Alessandro |
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Rok vydání: | 1994 |
Předmět: |
0301 basic medicine
Vincristine Friend leukemia 030106 microbiology Pharmacology Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Methionine Sulfoximine hemic and lymphatic diseases Tumor Cells Cultured medicine Animals Humans Pharmacology (medical) Doxorubicin Buthionine sulfoximine Buthionine Sulfoximine Chemistry Drug Synergism Glutathione medicine.disease Drug Resistance Multiple Multiple drug resistance Leukemia Infectious Diseases Oncology 030220 oncology & carcinogenesis medicine.drug K562 cells |
Zdroj: | Journal of Chemotherapy. 6:343-348 |
ISSN: | 1973-9478 1120-009X |
DOI: | 10.1080/1120009x.1994.11741170 |
Popis: | We have studied the interaction of glutathione-depleting concentrations of buthionine sulfoximine (BSO) with the anti-proliferative activity of doxorubicin (DXR) in three tumor lines, the mouse B16 melanoma. Friend erythroleukemia and the human K562 leukemia, both as DXR-sensitive and-resistant (with typical multidrug resistance) variants. BSO significantly enhanced the DXR effects in the wild-type Friend and K562 leukemias, and especially in the drug-resistant subline of Friend leukemia. BSO did not modify DXR accumulation and retention in the latter clone. Moreover, neither BSO nor verapamil used alone completely reversed the resistance to DXR of this cell line; their combination was more efficient and increased its drug sensitivity to a level closer to that of the parental counterpart. These results seem to indicate that the status of glutathione and of the enzymes related to it contributes to the resistance of Friend leukemia to DXR. An interesting additional finding was that BSO significantly synergizes with the antiproliferative effects of vincristine in the drug-sensitive variants of Friend and K562 leukemias. |
Databáze: | OpenAIRE |
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