The close association of π-class glutathione S-transferase with drug sensitivity to alkylating agents and cisplatin in human cancer cells

Toshiya Tanaka, Akira Yokomizo, Takeshi Uchiumi, Manabu Furukawa, Morimasa Wada, Michihiko Kuwano

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Abstract

Buthionine sulfoximine (BSO) is a synthetic amino acid that irreversibly inhibits glutathione biosynthesis. A BSO-resistant line, KB/BSO3, was established from human epidermoid cancer KB cells; and other BSO-resistant lines, HLE/BSO1 and HLE/BSO2, were from human hepatic cancer HLE cells. Cellular level of π-class glutathione S-transferase (GSTP1) in KB/BSO3 was less than 10% of the parental KB, and those in HLE/BSO1 and HLE/BSO2 was 30-40% of the parental HLE cells. KB/BSO3, HLE/BSO1 and HLE/BSO2 had collateral sensitivities to a potent anticancer agent, cisplatin, and alkylating agents including melphalan and nitrosourea. The GSTP1 cDNA transfectant KB/BSO3-π established from KB/BSO3, and also HLE/BSO1-π and HLE/BSO2-π established from HLE/BSO1 and HLE/BSO2, restored cellular sensitivities to cisplatin and alkylating agents to similar levels as KB and HLE cells. Our present results indicate that GSTP1 levels apparently limit cellular sensitivities to cisplatin and alkylating agents, suggesting that GSTP1 is a useful diagnostic marker for drug sensitivities to these agents in human cancer cells.

Original languageEnglish
Pages (from-to)1009-1014
Number of pages6
JournalInternational journal of oncology
Volume10
Issue number5
Publication statusPublished - Jan 1 1997

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Buthionine Sulfoximine
Alkylating Agents
Glutathione Transferase
Cisplatin
KB Cells
Pharmaceutical Preparations
Neoplasms
Melphalan
Liver Neoplasms
Antineoplastic Agents
Glutathione
Complementary DNA
Amino Acids

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

The close association of π-class glutathione S-transferase with drug sensitivity to alkylating agents and cisplatin in human cancer cells. / Tanaka, Toshiya; Yokomizo, Akira; Uchiumi, Takeshi; Furukawa, Manabu; Wada, Morimasa; Kuwano, Michihiko.

In: International journal of oncology, Vol. 10, No. 5, 01.01.1997, p. 1009-1014.

Research output: Contribution to journalArticle

Tanaka, Toshiya ; Yokomizo, Akira ; Uchiumi, Takeshi ; Furukawa, Manabu ; Wada, Morimasa ; Kuwano, Michihiko. / The close association of π-class glutathione S-transferase with drug sensitivity to alkylating agents and cisplatin in human cancer cells. In: International journal of oncology. 1997 ; Vol. 10, No. 5. pp. 1009-1014.
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