Mitochondria as a critical target of the chemotheraputic agent cisplatin in head and neck cancer.
Cisplatin is among the most important chemotherapeutic agents ever developed. It is a critical component of therapeutic regimens in a broad range of malignancies. However, more than a generation after its clinical introduction, the exact mechanism of cisplatin action on tumor cells is not fully defined. The preponderance of research over the last three decades has focused on cisplatin interactions with nuclear DNA which are felt to lead to apoptotic cell death in sensitive cells. However, recent data have shown that cisplatin may have important direct interactions with mitochondria which can induce apoptosis and may account for a significant portion of the clinical activity associated with this drug. These direct interactions between cisplatin and mitochondria may have critical implications for our understanding of this class of drugs and the development of new therapeutic agents.
Cullen
Kevin J
KJ
University of Maryland Marlene and Stewart Greenebaum Cancer Center, Baltimore, MD, USA. kcullen@umm.edu
Yang
Zejia
Z
Schumaker
Lisa
L
Guo
Zhongmin
Z
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use*; D045304:Cytochromes c / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D050994:Voltage-Dependent Anion Channels / Q000502:physiology*
D000970:Antineoplastic Agents; D050994:Voltage-Dependent Anion Channels; D045304:Cytochromes c; D002945:Cisplatin