Journal of Nippon Medical School: Vol.70 No.4 page.367

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ArticleTitle Cisplatin May Induce Frataxin Expression

AuthorList Mohammad Ghazizadeh

Affiliation Department of Molecular Pathology, Institute of Gerontology, Nippon Medical School

Language EN

Volume 70

Issue 4

Year 2003

Page 367-371

Received July 2, 2003

Accepted July 8, 2003

Keywords Cisplatin, resistance, reactive oxygen species, glutathione, Friedreich's ataxia, FRDA, frataxin, ovarian carcinoma cell line A2780

Abstract Cisplatin is a widely used drug in cancer chemotherapy and resistance to cisplatin is a major limitation for its successful application. Intracellular inactivation of cisplatin and detoxification of reactive oxygen species (ROS) by glutathione (a crucial cellular antioxidant) is a mechanism for cisplatin resistance. During cDNA microarray analyses of differential gene expression between a cisplatin-resistant A2780CP70 human ovarian carcinoma cell line and its parental A2780 cell line, we discovered that frataxin gene expression was frequently overexpressed in the cisplatin-resistant variant. Decreased expression of frataxin protein is associated with Friedreich's ataxia (FRDA) which is a neurodegenerative disease involving ROS-mediated cellular damage. Recent evidence suggests that frataxin might detoxify ROS via activation of glutathione peroxidase and elevation of thiols. To exploit potential involvement of frataxin gene in the development of resistance to cisplatin, we compared the levels of frataxin gene and protein in the cisplatin-resistant A2780CP70 ovarian carcinoma cell line and its parental A2780 cell line. We found that frataxin mRNA and protein expressions were elevated in the cisplatin-resistant cells. Our results suggest a potential role for cisplatin as an inducer of frataxin expression and implies that this gene may be a potential target for modulating the response to cisplatin. This is the first report showing an association between frataxin exprression and cisplatin resistance.

Correspondence to M. Ghazizadeh, MD, Department of Molecular Pathology, Institute of Gerontology, Nippon Medical School, 1-396 Kosugi-cho, Nakahara-ku, Kawasaki 211-8533, Japan
ciem@nms.ac.jp

ArticleTitle	Cisplatin May Induce Frataxin Expression
AuthorList	Mohammad Ghazizadeh
Affiliation	Department of Molecular Pathology, Institute of Gerontology, Nippon Medical School
Language	EN
Volume	70
Issue	4
Year	2003
Page	367-371
Received	July 2, 2003
Accepted	July 8, 2003
Keywords	Cisplatin, resistance, reactive oxygen species, glutathione, Friedreich's ataxia, FRDA, frataxin, ovarian carcinoma cell line A2780
Abstract	Cisplatin is a widely used drug in cancer chemotherapy and resistance to cisplatin is a major limitation for its successful application. Intracellular inactivation of cisplatin and detoxification of reactive oxygen species (ROS) by glutathione (a crucial cellular antioxidant) is a mechanism for cisplatin resistance. During cDNA microarray analyses of differential gene expression between a cisplatin-resistant A2780CP70 human ovarian carcinoma cell line and its parental A2780 cell line, we discovered that frataxin gene expression was frequently overexpressed in the cisplatin-resistant variant. Decreased expression of frataxin protein is associated with Friedreich's ataxia (FRDA) which is a neurodegenerative disease involving ROS-mediated cellular damage. Recent evidence suggests that frataxin might detoxify ROS via activation of glutathione peroxidase and elevation of thiols. To exploit potential involvement of frataxin gene in the development of resistance to cisplatin, we compared the levels of frataxin gene and protein in the cisplatin-resistant A2780CP70 ovarian carcinoma cell line and its parental A2780 cell line. We found that frataxin mRNA and protein expressions were elevated in the cisplatin-resistant cells. Our results suggest a potential role for cisplatin as an inducer of frataxin expression and implies that this gene may be a potential target for modulating the response to cisplatin. This is the first report showing an association between frataxin exprression and cisplatin resistance.
Correspondence to	M. Ghazizadeh, MD, Department of Molecular Pathology, Institute of Gerontology, Nippon Medical School, 1-396 Kosugi-cho, Nakahara-ku, Kawasaki 211-8533, Japan ciem@nms.ac.jp