Glutathione derivatives enhance adriamycin cytotoxicity in a human lung adenocarcinoma cell line

Yoichi Nakanishi, Hiroaki Matsuki, Koichi Takayama, Jun Yatsunami, Masayuki Kawasaki, Masayoshi Abe, Nobuyuki Hara

Research output: Contribution to journalArticle

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Abstract

We evaluated the effects of a panel of glutathione derivative (S-butyl, S-decyl, S-ethyl, S-heptyl, S-hexyl, S-methyl, S-nonyl, S-octyl, S-propyl and S-pentyl glutathiones) on glutathione-S-transferase activity in the cell lysates of a human lung cancer, PC-9. Glutathione derivatives inhibited glutathione S-transferase activity in PC-9 cell lysates by up to 67%. When PC-9 cells were incubated with the IC50 concentr ation of adriamycin (200 nM) and with nontoxic concentrations (1 μM) of the glutathione derivatives, cytotoxicity ranged from -20% to +55% of the control levels. Enhancement of adriamycin toxicity by glutathione derivatives was significantly correlated with the inhibition of glutathione-S-transferase activity. S-decyl-glutathione, which was one of the most potent inhibitors of glutathione-S-transferase activity, significantly enhanced the adriamycin-induced antitumor effect in vivo. Findings suggest that some glutathione derivatives, including the S-decyl, S-octyl, and S-hexyl glutathiones, enhance adriamycin-induced cytotoxicity, in part by inhibiting glutathione-S-transferase and that these agents may be useful as chemosensitizers for adriamycin therapy. In conclusion, the present results showed that some glutathione derivatives enhanced sensitivity of tumor cells to ADR by inhibiting GST activity. The use of BSO and EA as sensitizers to chemotherapy is currently being evaluated in clinical trials. The present data suggest that the use of GSH derivatives to modulate GST activity may improve the response to ADR.

Original languageEnglish
Pages (from-to)2129-2134
Number of pages6
JournalAnticancer Research
Volume17
Issue number3 C
Publication statusPublished - Aug 13 1997

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Doxorubicin
Glutathione
Cell Line
Glutathione Transferase
Adenocarcinoma of lung
Inhibitory Concentration 50
Lung Neoplasms
Clinical Trials
Drug Therapy
Neoplasms

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Nakanishi, Y., Matsuki, H., Takayama, K., Yatsunami, J., Kawasaki, M., Abe, M., & Hara, N. (1997). Glutathione derivatives enhance adriamycin cytotoxicity in a human lung adenocarcinoma cell line. Anticancer Research, 17(3 C), 2129-2134.

Glutathione derivatives enhance adriamycin cytotoxicity in a human lung adenocarcinoma cell line. / Nakanishi, Yoichi; Matsuki, Hiroaki; Takayama, Koichi; Yatsunami, Jun; Kawasaki, Masayuki; Abe, Masayoshi; Hara, Nobuyuki.

In: Anticancer Research, Vol. 17, No. 3 C, 13.08.1997, p. 2129-2134.

Research output: Contribution to journalArticle

Nakanishi, Y, Matsuki, H, Takayama, K, Yatsunami, J, Kawasaki, M, Abe, M & Hara, N 1997, 'Glutathione derivatives enhance adriamycin cytotoxicity in a human lung adenocarcinoma cell line', Anticancer Research, vol. 17, no. 3 C, pp. 2129-2134.
Nakanishi Y, Matsuki H, Takayama K, Yatsunami J, Kawasaki M, Abe M et al. Glutathione derivatives enhance adriamycin cytotoxicity in a human lung adenocarcinoma cell line. Anticancer Research. 1997 Aug 13;17(3 C):2129-2134.
Nakanishi, Yoichi ; Matsuki, Hiroaki ; Takayama, Koichi ; Yatsunami, Jun ; Kawasaki, Masayuki ; Abe, Masayoshi ; Hara, Nobuyuki. / Glutathione derivatives enhance adriamycin cytotoxicity in a human lung adenocarcinoma cell line. In: Anticancer Research. 1997 ; Vol. 17, No. 3 C. pp. 2129-2134.
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