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Mitochondrial Transcription Factor A and Mitochondrial Genome as Molecular Targets for Cisplatin-Based Cancer Chemotherapy.

Kohno K, Wang KY, Takahashi M, Kurita T, Yoshida Y, Hirakawa M, Harada Y, Kuma A, Izumi H, Matsumoto S - Int J Mol Sci (2015)

Bottom Line: Cisplatin is one of the most important chemotherapeutic agents and a key drug in therapeutic regimens for a broad range of solid tumors.Cisplatin may directly interact with mitochondria, which can induce apoptosis.The direct interactions between cisplatin and mitochondria may account for our understanding of the clinical activity of cisplatin and development of resistance.

View Article: PubMed Central - PubMed

Affiliation: Asahi Matsumoto Hospital, Kokuramimami-ku Tsuda, Kitakyushu-shi 800-0242, Japan. k-kohno@med.uoeh-u.ac.jp.

ABSTRACT
Mitochondria are important cellular organelles that function as control centers of the energy supply for highly proliferative cancer cells and regulate apoptosis after cancer chemotherapy. Cisplatin is one of the most important chemotherapeutic agents and a key drug in therapeutic regimens for a broad range of solid tumors. Cisplatin may directly interact with mitochondria, which can induce apoptosis. The direct interactions between cisplatin and mitochondria may account for our understanding of the clinical activity of cisplatin and development of resistance. However, the basis for the roles of mitochondria under treatment with chemotherapy is poorly understood. In this review, we present novel aspects regarding the unique characteristics of the mitochondrial genome in relation to the use of platinum-based chemotherapy and describe our recent work demonstrating the importance of the mitochondrial transcription factor A (mtTFA) expression in cancer cells.

No MeSH data available.


Related in: MedlinePlus

Cellular pathways and apoptosis induced by cisplatin. Cisplatin activates signal transduction pathways and may directly interact with mitochondria, which can induce apoptosis.
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ijms-16-19836-f001: Cellular pathways and apoptosis induced by cisplatin. Cisplatin activates signal transduction pathways and may directly interact with mitochondria, which can induce apoptosis.

Mentions: ROS generation occurs independently of the amount of cisplatin-induced nDNA damage and takes place in mitochondria as a consequence of the impairment of protein synthesis. The contribution of cisplatin-induced mitochondrial dysfunction in determining the cytotoxic effects of this drug varies among cells and depends on the mitochondrial redox status and integrity of mitochondrial DNA (mtDNA). Cisplatin-induced cellular pathways and responses are summarized in Figure 1.


Mitochondrial Transcription Factor A and Mitochondrial Genome as Molecular Targets for Cisplatin-Based Cancer Chemotherapy.

Kohno K, Wang KY, Takahashi M, Kurita T, Yoshida Y, Hirakawa M, Harada Y, Kuma A, Izumi H, Matsumoto S - Int J Mol Sci (2015)

Cellular pathways and apoptosis induced by cisplatin. Cisplatin activates signal transduction pathways and may directly interact with mitochondria, which can induce apoptosis.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4581328&req=5

ijms-16-19836-f001: Cellular pathways and apoptosis induced by cisplatin. Cisplatin activates signal transduction pathways and may directly interact with mitochondria, which can induce apoptosis.
Mentions: ROS generation occurs independently of the amount of cisplatin-induced nDNA damage and takes place in mitochondria as a consequence of the impairment of protein synthesis. The contribution of cisplatin-induced mitochondrial dysfunction in determining the cytotoxic effects of this drug varies among cells and depends on the mitochondrial redox status and integrity of mitochondrial DNA (mtDNA). Cisplatin-induced cellular pathways and responses are summarized in Figure 1.

Bottom Line: Cisplatin is one of the most important chemotherapeutic agents and a key drug in therapeutic regimens for a broad range of solid tumors.Cisplatin may directly interact with mitochondria, which can induce apoptosis.The direct interactions between cisplatin and mitochondria may account for our understanding of the clinical activity of cisplatin and development of resistance.

View Article: PubMed Central - PubMed

Affiliation: Asahi Matsumoto Hospital, Kokuramimami-ku Tsuda, Kitakyushu-shi 800-0242, Japan. k-kohno@med.uoeh-u.ac.jp.

ABSTRACT
Mitochondria are important cellular organelles that function as control centers of the energy supply for highly proliferative cancer cells and regulate apoptosis after cancer chemotherapy. Cisplatin is one of the most important chemotherapeutic agents and a key drug in therapeutic regimens for a broad range of solid tumors. Cisplatin may directly interact with mitochondria, which can induce apoptosis. The direct interactions between cisplatin and mitochondria may account for our understanding of the clinical activity of cisplatin and development of resistance. However, the basis for the roles of mitochondria under treatment with chemotherapy is poorly understood. In this review, we present novel aspects regarding the unique characteristics of the mitochondrial genome in relation to the use of platinum-based chemotherapy and describe our recent work demonstrating the importance of the mitochondrial transcription factor A (mtTFA) expression in cancer cells.

No MeSH data available.


Related in: MedlinePlus