RRC ID 45439
著者 Zhou X, Koizumi Y, Zhang M, Natsui M, Koyota S, Yamada M, Kondo Y, Hamada F, Sugiyama T.
タイトル Cadmium-coordinated supramolecule suppresses tumor growth of T-cell leukemia in mice.
ジャーナル Cancer Sci
Abstract 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 (TC4ATS-Cd) exhibits an anti-proliferative effect against T-cell leukemia cells. Cadmium exhibited cytotoxicity with IC50 values ranging from 36 to 129 μM against epithelia-derived cancer cell lines, while TC4ATS-Cd elicited no significant cytotoxicity (IC50 > 947 μM). However, a number of T-cell leukemia cell lines exhibited marked sensitivity to TC4ATS-Cd. In Jurkat cells, toxicity of TC4ATS-Cd occurred with an IC50 of 6.9 μM, which is comparable to that of 6.5 μM observed for cadmium alone. TC4ATS-Cd induced apoptotic cell death through activation of caspase-3 in Jurkat cells. In a xenograft model, TC4ATS-Cd (13 mg/kg) treatment significantly suppressed the tumor growth of Jurkat cells in mice. In addition, TC4ATS-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.
巻・号 106(5)
ページ 635-41
公開日 2015-5-1
DOI 10.1111/cas.12651
PMID 25735932
PMC PMC4452166
MeSH Animals Antineoplastic Agents / chemistry Antineoplastic Agents / pharmacology Apoptosis / drug effects Cadmium / pharmacokinetics Cadmium / toxicity Cadmium Compounds / pharmacology* Cell Line, Tumor Cell Proliferation / drug effects Coordination Complexes / chemistry Coordination Complexes / pharmacology Female Humans Inhibitory Concentration 50 Jurkat Cells / drug effects Leukemia, T-Cell / drug therapy* Leukemia, T-Cell / pathology Mice, SCID Phenols / chemistry Phenols / pharmacology* Xenograft Model Antitumor Assays
IF 4.966
引用数 13
WOS 分野 ONCOLOGY
リソース情報
ヒト・動物細胞 HPB-ALL(RCB1935) PEER(RCB1879) TE-4(RCB2097)