Significance of nuclear glutathione S-transferase pi in resistance to anti-cancer drugs.
Recent study has shown that nuclear glutathione S-transferase (GST) pi accumulates in cancer cells resistant to doxorubicin hydrochloride (DOX) and may function to prevent nuclear DNA damage caused by DOX (Goto et al., FASEB J., 15, 2702 - 2714 (2001)). It is not clear if the amount of nuclear GSTpi increases in response to other anti-cancer drugs and if so, what is the physiological significance of the nuclear transfer of GSTpi in the acquisition of drug-resistance in cancer cells. In the present study, we employed three cancer cell lines, HCT8 human colonic cancer cells, A549 human lung adenocarcinoma cells, and T98G human glioblastoma cells. We estimated the nuclear transfer of GSTpi induced by the anti-cancer drugs cisplatin (CDDP), irinotecan hydrochloride (CPT-11), etoposide (VP-16) and 5-fluorouracil (5-FU). It was found that: (1) Nuclear GSTpi accumulated in these cancer cells in response to CDDP, DOX, CPT-11, VP-16 and 5-FU. (2) An inhibitor of the nuclear transport of GSTpi, edible mushroom lectin (Agaricus bisporus lectin, ABL), increased the sensitivity of the cancer cells to DOX and CDDP, and partially to CPT-11. Treatment with ABL had no apparent effect on the cytotoxicity of VP-16 and 5-FU. These results suggest that inhibitors of the nuclear transfer of GSTpi have practical value in producing an increase of sensitivity to DOX, CDDP and CPT-11.
D021581:Active Transport, Cell Nucleus; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002467:Cell Nucleus / Q000201:enzymology*; D002945:Cisplatin / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D005472:Fluorouracil / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors / Q000502:physiology*; D006801:Humans; D000077146:Irinotecan; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000502:physiology*; D037102:Lectins / Q000494:pharmacology; D014407:Tumor Cells, Cultured
C041433:Agaricus lectins; D000970:Antineoplastic Agents; D007527:Isoenzymes; D037102:Lectins; D000077146:Irinotecan; D004317:Doxorubicin; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D005978:Glutathione; D002945:Cisplatin; D005472:Fluorouracil; D002166:Camptothecin