Relationship of glutathione and glutathione-S-transferase to cisplatin sensitivity in human head and neck squamous carcinoma cell lines

Seth A. Yellin, Bruce J. Davidson, John T. Pinto, Peter G. Sacks, Changhong Qiao, Stimson P. Schantz

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

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.

Original languageEnglish
Pages (from-to)223-232
Number of pages10
JournalCancer Letters
Volume85
Issue number2
DOIs
StatePublished - 14 Oct 1994
Externally publishedYes

Keywords

  • Cisplatin
  • Glutathione
  • Glutathione-S-transferase
  • Head and neck carcinoma
  • S-Allyl cysteine

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