| Literature DB >> 15958539 |
Mari Shimura1, Akira Saito, Satoshi Matsuyama, Takahiro Sakuma, Yasuhito Terui, Kazumasa Ueno, Hirokatsu Yumoto, Kazuto Yamauchi, Kazuya Yamamura, Hidekazu Mimura, Yasuhisa Sano, Makina Yabashi, Kenji Tamasaku, Kazuto Nishio, Yoshinori Nishino, Katsuyoshi Endo, Kiyohiko Hatake, Yuzo Mori, Yukihito Ishizaka, Tetsuya Ishikawa.
Abstract
Minerals are important for cellular functions, such as transcription and enzyme activity, and are also involved in the metabolism of anticancer chemotherapeutic compounds. Profiling of intracellular elements in individual cells could help in understanding the mechanism of drug resistance in tumors and possibly provide a new strategy of anticancer chemotherapy. Using a recently developed technique of scanning X-ray fluorescence microscopy (SXFM), we analyzed intracellular elements after treatment with cis-diamminedichloro-platinum(II) (CDDP), a platinum-based anticancer agent. The images obtained by SXFM (element array) revealed that the average Pt content of CDDP-resistant cells was 2.6 times less than that of sensitive cells, and the zinc content was inversely correlated with the intracellular Pt content. Data suggested that Zn-related detoxification is responsible for resistance to CDDP. Of Zn-related excretion factors, glutathione was highly correlated with the amount of Zn. The combined treatment of CDDP and a Zn(II) chelator resulted in the incorporation of thrice more Pt with the concomitant down-regulation of glutathione. We propose that the generation of an element array by SXFM opens up new avenues in cancer biology and treatment.Entities:
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Year: 2005 PMID： 15958539 DOI： 10.1158/0008-5472.CAN-05-0373
Source DB: PubMed Journal: Cancer Res ISSN： 0008-5472 Impact factor: 12.701