Cadmium-coordinated supramolecule suppresses tumor growth of T-cell leukemia in mice.
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.
Department of Biochemistry, Akita University Graduate School of Medicine, Akita, Japan.|Venture Business Laboratory, Akita University, Akita, Japan.
Xiaoping
X
Zhou
Department of Biochemistry, Akita University Graduate School of Medicine, Akita, Japan.
Yukio
Y
Koizumi
Department of Biochemistry, Akita University Graduate School of Medicine, Akita, Japan.
Muxin
M
Zhang
Department of Biochemistry, Akita University Graduate School of Medicine, Akita, Japan.
Miyuki
M
Natsui
Department of Biochemistry, Akita University Graduate School of Medicine, Akita, Japan.
Souichi
S
Koyota
Research Center for Engineering Science, Graduate School of Engineering and Resource Science, Akita University, Akita, Japan.
Manabu
M
Yamada
Department of Life Science, Graduate School of Engineering and Resource Science, Akita University, Akita, Japan.
Yoshihiko
Y
Kondo
Applied Chemistry, Graduate School of Engineering and Resource Science, Akita University, Akita, Japan.
Fumio
F
Hamada
Department of Biochemistry, Akita University Graduate School of Medicine, Akita, Japan.
Toshihiro
T
Sugiyama
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002104:Cadmium / Q000493:pharmacokinetics / Q000633:toxicity; D019187:Cadmium Compounds / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D019169:Jurkat Cells / Q000187:drug effects; D015458:Leukemia, T-Cell / Q000188:drug therapy* / Q000473:pathology; D016513:Mice, SCID; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D019187:Cadmium Compounds; D056831:Coordination Complexes; D010636:Phenols; C446239:thiacalix(4)arenetetrasulfonate; D002104:Cadmium
Cadmium; T-cell receptor; leukemia; supramolecule; thiacalixarene