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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

Cisplatin-induced signaling, cisplatin resistance and transcription system in cancer cells discussed in this review. mtTFA functions in both nuclei and mitochondria to not only interact with cisplatin-modified DNA, but also regulate the nuclear and mitochondrial gene expression.
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ijms-16-19836-f002: Cisplatin-induced signaling, cisplatin resistance and transcription system in cancer cells discussed in this review. mtTFA functions in both nuclei and mitochondria to not only interact with cisplatin-modified DNA, but also regulate the nuclear and mitochondrial gene expression.

Mentions: ZNF143 has been shown to be a cisplatin-inducible gene that regulates the mitochondrial ribosomal protein S11 [57]. Interestingly, there is one ZNF143 binding region in the promoter region of the mtTFA gene. The involvement of ZNF143 in cell growth and the protection of cells from oxidative damage, as well as the effects of cisplatin treatment, has recently been reported [35,58,59]. Furthermore, a strong ZNF143 expression was previously found to show a significant correlation with pathologically moderate to poor differentiation and highly invasive characteristics in 183 paraffin-embedded tumor samples from patients with lung adenocarcinoma [60]. Based on these reports, we next discuss the clinical implications of mtTFA. A schematic summary of the mutual relationship of transcription factors, including mtTFA, is shown in Figure 2 and the major factors described in this review are listed with detailed information in Table 2.


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)

Cisplatin-induced signaling, cisplatin resistance and transcription system in cancer cells discussed in this review. mtTFA functions in both nuclei and mitochondria to not only interact with cisplatin-modified DNA, but also regulate the nuclear and mitochondrial gene expression.
© Copyright Policy
Related In: Results  -  Collection

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

ijms-16-19836-f002: Cisplatin-induced signaling, cisplatin resistance and transcription system in cancer cells discussed in this review. mtTFA functions in both nuclei and mitochondria to not only interact with cisplatin-modified DNA, but also regulate the nuclear and mitochondrial gene expression.
Mentions: ZNF143 has been shown to be a cisplatin-inducible gene that regulates the mitochondrial ribosomal protein S11 [57]. Interestingly, there is one ZNF143 binding region in the promoter region of the mtTFA gene. The involvement of ZNF143 in cell growth and the protection of cells from oxidative damage, as well as the effects of cisplatin treatment, has recently been reported [35,58,59]. Furthermore, a strong ZNF143 expression was previously found to show a significant correlation with pathologically moderate to poor differentiation and highly invasive characteristics in 183 paraffin-embedded tumor samples from patients with lung adenocarcinoma [60]. Based on these reports, we next discuss the clinical implications of mtTFA. A schematic summary of the mutual relationship of transcription factors, including mtTFA, is shown in Figure 2 and the major factors described in this review are listed with detailed information in Table 2.

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