Details

Autor(en) / Beteiligte

• Hamilton, Thomas C.
• Winker, Margaret A.
• Louie, Karen G.
• Batist, Gerald
• Behrens, Brent C.
• Tsuruo, Takashi
• Grotzinger, Karen R.
• McKoy, Wilma M.
• Young, Robert C.
• Ozols, Robert F.

Titel

Augmentation of adriamycin, melphalan, and cisplatin cytotoxicity in drug-resistant and -sensitive human ovarian carcinoma cell lines by buthionine sulfoximine mediated glutathione depletion

Ist Teil von

• Biochemical pharmacology, 1985-07, Vol.34 (14), p.2583-2586

Ort / Verlag

New York, NY: Elsevier Inc

Erscheinungsjahr

1985

Quelle

Access via ScienceDirect (Elsevier)

Beschreibungen/Notizen

• The development of acquired resistance to antineoplastic drugs and the associated broad cross-resistance to other agents frequently limits the effectiveness of chemotherapy. Ling and coworkers have demonstrated that Chinese hamster ovary (CHO) cells develop the phenotype of pleiotropic drug resistance which is manifest by a decrease in drug accumulation in these cells and hence a decrease in cytotoxicity (1). The role of drug accumulation and membrane glycoproteins in the expression of primary resistance and cross-resistance in human tumors is an area of active investigation (2–4). We have developed a series of human ovarian cancer cell lines with acquired resistance to melphalan, cisplatin, or adriamycin (5). These cell lines exhibit sensitivity/resistance profiles characteristic of pleiotropic drug resistance. In addition, the melphalan and cisplatin resistant variants are also cross-resistant to irradiation (6). Both the primary resistance to melphalan and the cross-resistance to irradiation in these cell lines can be reversed by lowering glutathione (GSH) levels in the cells with buthionine sulfoximine (BSO) (6,7). In the present study, the role of GSH in the expression of sensitivity to agents other than melphalan was examined by BSO-mediated depletion of GSH. In addition, the patterns of both primary resistance and cross-resistance were compared following GSH depletion in these cell lines.