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
Rok vydání: 1994
Předmět:
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