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Cadmium‐coordinated supramolecule suppresses tumor growth of T ‐cell leukemia in mice
Author(s) -
Zhou Xiaoping,
Koizumi Yukio,
Zhang Muxin,
Natsui Miyuki,
Koyota Souichi,
Yamada Manabu,
Kondo Yoshihiko,
Hamada Fumio,
Sugiyama Toshihiro
Publication year - 2015
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12651
Subject(s) - jurkat cells , cytotoxicity , cadmium , chemistry , cytotoxic t cell , apoptosis , t cell leukemia , cell culture , leukemia , cisplatin , cell growth , microbiology and biotechnology , cancer research , t cell , biochemistry , biology , immunology , medicine , in vitro , chemotherapy , organic chemistry , genetics , immune system
Cadmium is a toxic pollutant with occupational and environmental significance, due to its diverse toxic effects. Supramolecules that conjugate and decontaminate toxic metals have potential for use in treatment of cadmium intoxication. In addition, metal‐coordinating ability has been postulated to contribute to the cytotoxic effects of anti‐tumor agents such as cisplatin or bleomycin. Thiacalixarenes, cyclic oligomers of p ‐alkylphenol bridged by sulfur atoms, are supramolecules known to have potent coordinating ability to metal ions. In this study, we show that cadmium‐coordinated thiacalix[4]arene tetrasulfate ( TC 4 ATS ‐Cd) exhibits an anti‐proliferative effect against T‐cell leukemia cells. Cadmium exhibited cytotoxicity with IC 50 values ranging from 36 to 129 μM against epithelia‐derived cancer cell lines, while TC 4 ATS ‐Cd elicited no significant cytotoxicity ( IC 50  > 947 μM). However, a number of T‐cell leukemia cell lines exhibited marked sensitivity to TC 4 ATS ‐Cd. In Jurkat cells, toxicity of TC 4 ATS ‐Cd occurred with an IC 50 of 6.9 μM, which is comparable to that of 6.5 μM observed for cadmium alone. TC 4 ATS ‐Cd induced apoptotic cell death through activation of caspase‐3 in Jurkat cells. In a xenograft model, TC 4 ATS ‐Cd (13 mg/kg) treatment significantly suppressed the tumor growth of Jurkat cells in mice. In addition, TC 4 ATS ‐Cd‐treated mice exhibited significantly less cadmium accumulation in liver and kidney compared to equimolar cadmium‐treated mice. These results suggest that cadmium‐coordinated supramolecules may have therapeutic potential for treatment of T‐cell leukemia.

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