[Cisplatin sensitivity transcriptional factor and mitochondrial DNA maintenance protein].
Cisplatin is one of the most commonly used chemotherapeutic agents, with demonstrated activity against a diverse spectrum of malignancies, including testicular cancer, ovarian carcinoma, and head/neck tumors. However, the therapeutic efficacy of the drug is limited by the severity of its side effects and the potential progression of tumor cells to a cisplatin-resistant state. We found that the transcription factors of genes involved in cisplatin resistance are often overexpressed or activated in cisplatin-resistant cells. In this paper, we describe ATF4, Clock, ZNF143, and YB-1 as cisplatin resistance genes. Clock and the ATF4 transcription system might play an important role in multidrug resistance through the glutathione-dependent redox system, and the physiological potential of the Clock-controlled redox system might be important to better understand oxidative stress-associated disorders including cancer and systemic chronotherapy. We also describe the basis for understanding the effects of cisplatin on mitochondrial activity and the mechanisms of cellular toxicity and resistance caused by this drug.
Uchiumi
Takeshi
T
Department of Clinical Chemistry and Laboratory Medicine, Graduated School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. uchiumi@cclm.med.kyushu-u.ac.jp
Knag
Donchon
D
D051701:Activating Transcription Factor 4 / Q000502:physiology; D056926:CLOCK Proteins; D002945:Cisplatin / Q000494:pharmacology*; D018432:Drug Resistance, Multiple / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D006801:Humans; D024101:Mitochondrial Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics; D014157:Transcription Factors / Q000032:analysis*; D016335:Zinc Fingers / Q000502:physiology
D024101:Mitochondrial Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D051701:Activating Transcription Factor 4; D056926:CLOCK Proteins; D002945:Cisplatin