Element array by scanning X-ray fluorescence microscopy after cis-diamminedichloro-platinum(II) treatment.
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.
Shimura
Mari
M
Department of Intractable Diseases, International Medical Center of Japan, Tokyo.
Saito
Akira
A
Matsuyama
Satoshi
S
Sakuma
Takahiro
T
Terui
Yasuhito
Y
Ueno
Kazumasa
K
Yumoto
Hirokatsu
H
Yamauchi
Kazuto
K
Yamamura
Kazuya
K
Mimura
Hidekazu
H
Sano
Yasuhisa
Y
Yabashi
Makina
M
Tamasaku
Kenji
K
Nishio
Kazuto
K
Nishino
Yoshinori
Y
Endo
Katsuyoshi
K
Hatake
Kiyohiko
K
Mori
Yuzo
Y
Ishizaka
Yukihito
Y
Ishikawa
Tetsuya
T
D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000494:pharmacology; D002945:Cisplatin / Q000493:pharmacokinetics / Q000494:pharmacology*; D004347:Drug Interactions; D019008:Drug Resistance, Neoplasm; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008658:Inactivation, Metabolic; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D008668:Metallothionein / Q000378:metabolism; D008856:Microscopy, Fluorescence / Q000379:methods; D010984:Platinum / Q000493:pharmacokinetics; D013052:Spectrometry, X-Ray Emission / Q000379:methods; D015032:Zinc / Q000378:metabolism
D000970:Antineoplastic Agents; D002614:Chelating Agents; D010984:Platinum; D008668:Metallothionein; D005978:Glutathione; D015032:Zinc; D002945:Cisplatin