Heterocyclic Organobismuth(III) Compound Targets Tubulin to Induce G_2/M Arrest in HeLa Cells
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概要
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Our previous study showed that organobismuth compounds induce apoptosis in human promyelocytic leukemia cells, although solid tumor cell lines were relatively resistant. Herein, we investigated the primary cellular target of these compounds in HeLa cells. One organobismuth compound, bi-chlorodibenzo[c,f][1,5]thiabismocine (compound 3), arrested the cell cycle at G2/M as assessed by flow cytometry and by upregulating the expression of cyclin B1. At a low concentration (0.5 μM), compound 3 caused cell cycle arrest at the mitotic phase and induced apoptosis. At a higher concentration (>1.0 μM), it induced an arrest in the G2/M phase, leading to apoptosis. In many cells blocked at the M phase, the organization of microtubules was affected, indicating depolymerization of the microtubule network. Western blotting demonstrated that compound 3 depolymerized microtubules similar to colchicine and nocodazole. Experiments in vitro also showed that compound 3 inhibited the assembly of purified tubulin in a concentration-dependent manner by interacting with the colchicine-binding site of tubulin through its SH groups. Heterocyclic organobismuth compounds are novel tubulin ligands.
- 2009-04-20
著者
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Akagi Kiwamu
Division Of Molecular Diagnosis And Cancer Prevention Saitama Cancer Center
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YAGURA Tatsuo
Department of Bioscience, Faculty of Science and Technology, Kwansei-Gakuin University
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Yagura Tatsuo
Department Of Biology Faculty Of Science Hokkaido University:(present)department Of Immunology And V
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IUCHI Katsuya
Department of Bioscience, Faculty of Science and Technology, Kwansei Gakuin University
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Iuchi Katsuya
Department Of Bioscience Faculty Of Science And Technology Kwansei Gakuin University
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