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Title :Tumor-selective cytotoxicity of nitidine results from its rapid accumulation into mitochondria
Authors :Iwasaki, Hironori
Inafuku, Masashi
Taira, Naoyuki
Saito, Seikoh
Oku, Hirosuke
Issue Date :26-Apr-2017
Abstract :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 ofNTD-induced cell death is independent of the cell cycle. Short-termtreatment 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 fromunique 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.Thedrug 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
URL :https://doi.org/10.1155/2017/2130594
Type Local :雑誌掲載論文
ISSN :2314-6133
Publisher :Hindawi Publishing Corporation
URI :http://hdl.handle.net/20.500.12000/37586
Citation :BioMed Research International Vol.2017
Appears in Collections:Peer-reviewed Journal Articles(Tropical Biosphere Research Center)

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