Glutathione S-transferase P1 has protective effects on cell viability against camptothecin

Hara, Takamitsu; Ishii, Takeo; Fujishiro, Mina; Masuda, Michiaki; Ito, Takaaki; Nakajima, Jun; Inoue, Tomio; Matsuse, Takeshi

doi:10.1016/j.canlet.2003.09.005

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Volume 203, Issue 2 , Pages 199-207, January 2004

Glutathione S-transferase P1 has protective effects on cell viability against camptothecin

Takamitsu Hara
- Department of Radiology, Yokohama City University School of Medicine, Yokohama City, Japan
Takeo Ishii
- Department of Pulmonary Medicine, Yokohama City University Medical Center, 4-57, Urahune-cho, Minami-ku, Yokohama City 232-0024, Japan
- Research Fellow of the Japan Society for the Promotion of Science.
Mina Fujishiro
- Department of Pulmonary Medicine, Yokohama City University Medical Center, 4-57, Urahune-cho, Minami-ku, Yokohama City 232-0024, Japan
Michiaki Masuda
- Department of Microbiology, Dokkyo University School of Medicine, Dokkyo, Japan
Takaaki Ito
- Department of Pathology, Yokohama City University School of Medicine, Yokohama City, Japan
Jun Nakajima
- Department of Cardiothoracic Surgery, University of Tokyo, Tokyo, Japan
Tomio Inoue
- Department of Radiology, Yokohama City University School of Medicine, Yokohama City, Japan
Takeshi Matsuse
- Department of Pulmonary Medicine, Yokohama City University Medical Center, 4-57, Urahune-cho, Minami-ku, Yokohama City 232-0024, Japan
- Corresponding author. Tel.: +81-45-261-5656; fax: +81-45-241-2812

Received 17 June 2003; received in revised form 25 August 2003; accepted 1 September 2003.

Abstract

Glutathione S-transferase P1 (GSTP1) is one of the important xenobiotic-metabolizing enzymes. It was reported that GSTP1 was overexpressed in malignant tissues, and its expression level was associated with resistance to chemotherapeutics.

We carried out transfection of GSTP1 sense and antisense vectors to examine effects of GSTP1 on cell cycle arrest and apoptosis induced by camptothecin in HeLa cells.

Transfection of GSTP1 antisense vector induced apoptosis. Camptothecin-induced S- or G2/M arrest was intensified by transfection of GSTP1 antisense vector, and subsequent apoptosis was attenuated by transfection of GSTP1 sense vector. These results suggest that GSTP1 has protective effects against camptothecin-induced cytotoxicity.

Keywords: Glutathione S-transferase P1, Camptothecin, Cell cycle arrest, Apoptosis