Relationship of glutathione and glutathione-S-transferase to cisplatin sensitivity in human head and neck squamous carcinoma cell lines Journal Article
| Authors: | Yellin, S. A.; Davidson, B. J.; Pinto, J. T.; Sacks, P. G.; Qiao, C.; Schantz, S. P. |
| Article Title: | Relationship of glutathione and glutathione-S-transferase to cisplatin sensitivity in human head and neck squamous carcinoma cell lines |
| Abstract: | Factors controlling glutathione metabolism may govern sensitivity to chemotherapeutic agents such as cisplatin. Using a battery of cell lines derived from previously untreated head and neck squamous cell carcinomas, we examined cisplatin resistance relative to (a) glutathione-S-transferase (GST)-π gene amplification and expression, (b) basal and inducible GST-total and GST-π enzymatic activity, and (c) cellular levels of reduced glutathione (GSH). Using Southern blot analysis and northern blot hybridization, no relationship between GST-π gene amplification, mRNA expression and drug resistance could be identified. Despite the capacity of cisplatin to induce GST enzyme activity, the response was variable and unrelated to cisplatin responsiveness. However, an inverse relationship between GSH levels and cisplatin sensitivity was identified. To further clarify these effects, cells were treated with S-allyl cysteine (SAC), a thioallyl derivative isolated from garlic (Allium sativum), which altered cellular GSH in a biphasic manner. Pretreatment with SAC to lower cellular GSH levels followed by exposure to cisplatin significantly enhanced the cytotoxic effects of cisplatin, while SAC alone had no effect on cell growth. © 1994. |
| Keywords: | controlled study; human cell; squamous cell carcinoma; carcinoma, squamous cell; cisplatin; cell survival; gene amplification; gene expression; antineoplastic activity; drug effect; drug resistance; tumor cells, cultured; enzyme activity; gene expression regulation, neoplastic; antiinfective agent; messenger rna; head and neck neoplasms; rna, messenger; glutathione transferase; drug cytotoxicity; drug sensitivity; chromosomes, human, pair 11; allium sativum; glutathione; cysteine; head and neck carcinoma; in vitro; northern blotting; southern blotting; cysteine derivative; glutathione-s-transferase; human; priority journal; article; support, u.s. gov't, p.h.s.; glutathione metabolism; s-allyl cysteine; sativum |
| Journal Title: | Cancer Letters |
| Volume: | 85 |
| Issue: | 2 |
| ISSN: | 0304-3835 |
| Publisher: | Elsevier Ireland Ltd. |
| Date Published: | 1994-10-14 |
| Start Page: | 223 |
| End Page: | 232 |
| Language: | English |
| DOI: | 10.1016/0304-3835(94)90279-8 |
| PROVIDER: | scopus |
| PUBMED: | 7954341 |
| DOI/URL: | |
| Notes: | Corrigendum issued, see DOI 10.1016/0304-3835(95)03728-F -- Export Date: 14 January 2019 -- Article -- Source: Scopus |
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