https://scholars.lib.ntu.edu.tw/handle/123456789/562949
標題: | Arsenic trioxide sensitivity is associated with low level of glutathione in cancer cells | 作者: | CHIH-HSIN YANG Kuo M.-L. Chen J.-C. YAO-CHANG CHEN |
公開日期: | 1999 | 卷: | 81 | 期: | 5 | 起(迄)頁: | 796-799 | 來源出版物: | British Journal of Cancer | 摘要: | Arsenic trioxide (As2O3) is a novel anticancer agent, which has been found to induce remission in acute promyelocytic leukaemic patients following daily intravenous administration. The therapeutic Value of As2O3 in other cancers is still largely unknown. Cytotoxic tests in a panel of cancer cell lines showed that bladder cancer, acute promyelocytic leukaemic and gastrointestinal cancer cells were the most sensitive to As2O3 among 17 cell lines tested. Cellular glutathione (GSH) system plays an important role in arsenic detoxification in mammalian cells. Cancer cells that were intrinsically sensitive to As2O3 contained lower levels of GSH, whereas resistant cancer cells contained higher levels of GSH. On the other hand, there was no association of glutathione-S-transferase-Π or multidrug resistance-associated protein 1 levels with arsenic sensitivity in these cancer cells. Multidrug-resistant cancer cells that were cross-resistant to arsenic contained higher levels of GSH or multidrug-resisiance-associated protein 1 than their drug-sensitive parental cells. Cancer cells become more sensitive to arsenic after depletion of cellular GSH with L-buthionine sulphoximine. We concluded that cellular GSH level is the most important determinant of arsenic sensitivity in cancer cells. Cellular GSH level and its modulation by buthionine sulphoximine should be considered in designing clinical trials using arsenic in solid tumours. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/562949 | ISSN: | 0007-0920 | DOI: | 10.1038/sj.bjc.6690766 | SDG/關鍵字: | antineoplastic agent; arsenic trioxide; glutathione; glutathione transferase; imine; multidrug resistance protein; acute myeloblastic leukemia; article; bladder cancer; cancer cell culture; cancer regression; cell level; cross resistance; digestive system cancer; drug cytotoxicity; drug detoxification; drug sensitivity; human; human cell; intravenous drug administration; mammal cell; priority journal; Antimetabolites, Antineoplastic; Antineoplastic Agents; Arsenicals; Buthionine Sulfoximine; DNA-Binding Proteins; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Glutathione; Glutathione S-Transferase pi; Glutathione Transferase; Humans; Isoenzymes; Multidrug Resistance-Associated Proteins; Oxides; Tumor Cells, Cultured |
顯示於: | 醫學院附設醫院 (臺大醫院) |
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