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GSTP1 affects chemoresistance against camptothecin in human lung adenocarcinoma cells

Takeo Ishii1, Shinji Teramoto, Takeshi Matsuse

  • 1Department of Pulmonary Medicine, Yokohama City University Medical Center, 4-57, Urahune-cho, Minami-ku, Yokohama City 232-0024, Japan.

Cancer Letters
|October 27, 2004
PubMed

Insights

Glutathione S-transferase P1 (GSTP1) protects certain lung cancer cells from camptothecin-induced death. Its protective role in chemoresistance appears linked to glutathione conjugation, not JNK inhibition.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Glutathione S-transferase P1 (GSTP1) functions as a xenobiotic enzyme and a Jun N-terminal kinase (JNK) inhibitor.
  • Lung adenocarcinoma is a significant form of lung cancer with varying responses to chemotherapy.

Purpose of the Study:

  • To investigate the role of GSTP1 in chemoresistance against camptothecin in human lung adenocarcinoma cells.
  • To determine the mechanism by which GSTP1 influences camptothecin-induced cell death.

Main Methods:

  • Investigated GSTP1 expression in response to camptothecin.
  • Utilized gene downregulation techniques to assess GSTP1's impact on camptothecin-induced necrosis.
  • Employed JNK inhibitor (SP600125) and glutathione depletion (l-buthionine-sulfoximine) to elucidate the mechanism.

Main Results:

  • Camptothecin treatment upregulated GSTP1 expression.
  • Downregulation of GSTP1 increased camptothecin-induced necrosis in A549 cells, but not in PC-14 or RERF-LC-KJ cells.
  • The protective effect of GSTP1 in A549 cells was primarily mediated by glutathione conjugation, with minimal involvement of JNK inhibition.

Conclusions:

  • GSTP1 confers protective effects against camptothecin-induced necrosis in a subset of human lung adenocarcinoma cells.
  • The mechanism of protection involves GSTP1's role in glutathione conjugation.
  • Findings highlight GSTP1 as a potential therapeutic target for enhancing lung adenocarcinoma chemotherapy.

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