Cadmium-coordinated supramolecule suppresses tumor growth of T-cell leukemia in mice.
Cadmium-coordinated supramolecule suppresses tumor growth of T-cell leukemia in mice.
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DOI：
10.1111/cas.12651
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发表时间：
2015-05
期刊：
影响因子：
5.7
通讯作者：
Sugiyama T
中科院分区：
文献类型：
--
作者：
Zhou X;Koizumi Y;Zhang M;Natsui M;Koyota S;Yamada M;Kondo Y;Hamada F;Sugiyama T
镉因其多种毒性作用而成为一种具有职业和环境意义的有毒污染物。缀合和净化有毒金属的超分子具有用于治疗镉中毒的潜力。此外，金属配位能力被认为有助于顺铂或博莱霉素等抗肿瘤药物的细胞毒性作用。硫杂杯芳烃是由硫原子桥联的对烷基苯酚的环状低聚物，是已知对金属离子具有有效配位能力的超分子。在这项研究中，我们发现镉配位的硫杂环[4]芳烃四硫酸盐 (TC4ATS-Cd) 对 T 细胞白血病细胞具有抗增殖作用。镉对上皮来源的癌细胞系表现出细胞毒性，IC50 值范围为 36 至 129 μM，而 TC4ATS-Cd 没有引起显着的细胞毒性 (IC50 > 947 μM)。然而，许多 T 细胞白血病细胞系对 TC4ATS-Cd 表现出明显的敏感性。在 Jurkat 细胞中，TC4ATS-Cd 发生毒性，IC50 为 6.9 μM，与单独镉观察到的 6.5 μM 相当。 TC4ATS-Cd 通过激活 Jurkat 细胞中的 caspase-3 诱导细胞凋亡。在异种移植模型中，TC4ATS-Cd (13 mg/kg) 治疗显着抑制小鼠 Jurkat 细胞的肿瘤生长。此外，与等摩尔镉处理的小鼠相比，TC4ATS-Cd处理的小鼠在肝脏和肾脏中的镉积累显着减少。这些结果表明镉配位超分子可能具有治疗 T 细胞白血病的潜力。
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.
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影响因子：
1.8
作者：
Kumagai, H;Hasegawa, M;Miyano, S
通讯作者：
Miyano, S
影响因子：
3.3
作者：
Coleman, Anthony W.;Jebors, Said;Moulin, Marcelle
通讯作者：
Moulin, Marcelle
影响因子：
3.5
作者：
Inaba, T;Kobayashi, E;Nogawa, K
通讯作者：
Nogawa, K
影响因子：
3.9
作者：
Aydin, HH;Celik, HA;Batur, Y
通讯作者：
Batur, Y
影响因子：
3
作者：
MARCOVECCHIO, JE;MORENO, VJ
通讯作者：
MORENO, VJ