Tumor-Selective Cytotoxicity of Nitidine Results from Its Rapid Accumulation into Mitochondria.

We identified a nitidine- (NTD-) accumulating organelle and evaluated the net cytotoxicity of accumulated NTD. To evaluate tumor cell selectivity of the drug, we evaluated its selective cytotoxicity against 39 human cancer cell lines (JFCR39 panel), and the profile was compared with those of known a...

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Publicado en:BioMed Research International Vol. 2017; pp. 1 - 11
Autores principales: Iwasaki, Hironori, Inafuku, Masashi, Taira, Naoyuki, Saito, Seikoh, Oku, Hirosuke
Formato: equations & formulas pictorial research tables/charts Journal Article
Publicado: Wiley-Blackwell 4/26/2017
Acceso en línea:Ver este registro en EBSCOhost
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      dt: 4/26/2017
      vid: 2017
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      pub: Wiley-Blackwell
      place: Malden, Massachusetts
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        10.1155/2017/2130594
        122712334
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        atl: Tumor-Selective Cytotoxicity of Nitidine Results from Its Rapid Accumulation into Mitochondria.
      aug:
        au:
          Iwasaki, Hironori
          Inafuku, Masashi
          Taira, Naoyuki
          Saito, Seikoh
          Oku, Hirosuke
        affil: Tropical Biosphere Research Center, University of the Ryukyus, Nishihara, Okinawa 903-0213, Japan
      sug:
        subj:
          Cytotoxins
          Mitochondria
          Organelles
          Human
          Research Methodology
          Neoplasms Drug Therapy
      ab: We identified a nitidine- (NTD-) accumulating organelle and evaluated the net cytotoxicity of accumulated NTD. To evaluate tumor cell selectivity of the drug, we evaluated its selective cytotoxicity against 39 human cancer cell lines (JFCR39 panel), and the profile was compared with those of known anticancer drugs. Organelle specificity of NTD was visualized using organelle-targeted fluorescent proteins. Real-time analysis of cell growth, proliferation, and cytotoxicity was performed using the xCELLigence system. Selectivity of NTD in the JFCR39 panel was evaluated. Mitochondria-specific accumulation of NTD was observed. Real-time cytotoxicity analysis suggested that the mechanism of NTD-induced cell death is independent of the cell cycle. Short-term treatment indicated that this cytotoxicity only resulted from the accumulation of NTD into the mitochondria. The results from the JFCR39 panel indicated that NTD-mediated cytotoxicity resulted from unique mechanisms compared with those of other known anticancer drugs. These results suggested that the cytotoxicity of NTD is only induced by its accumulation in mitochondria. The drug triggered mitochondrial dysfunction in less than 2 h. Similarity analysis of the selectivity of NTD in 39 tumor cell lines strongly supported the unique tumor cell specificity of NTD. Thus, these features indicate that NTD may be a promising antitumor drug for new combination chemotherapies.
      pubtype: Academic Journal
      doctype:
        equations & formulas
        pictorial
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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