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[Cancer Research 59, 776-780, February 1, 1999]
© 1999 American Association for Cancer Research
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[Cancer Research 59, 776-780, February 15, 1999]
© 1999 American Association for Cancer Research

Advances in Brief

Arsenic Targets Tubulins to Induce Apoptosis in Myeloid Leukemia Cells

Yong Ming Li1 and John D. Broome

Department of Laboratories, North Shore University Hospital, Manhasset, New York 11030 and Department of Pathology, New York University School of Medicine, New York, New York 10016

Arsenic exhibits a differential toxicity to cancer cells. At a high concentration (>5 µM), As2O3 causes acute necrosis in various cell lines. At a lower concentration (0.5–5 µM), it induces myeloid cell maturation and an arrest in metaphase, leading to apoptosis. As2O3-treated cells have features found with both tubulin-assembling enhancers (Taxol) and inhibitors (colchicine). Prior treatment of monomeric tubulin with As2O3 markedly inhibits GTP-induced polymerization and microtubule formation in vitro but does not destabilize GTP-induced tubulin polymers. Cross-inhibition experiments indicate that As2O3 is a noncompetitive inhibitor of GTP binding to tubulin. These observations correlate with the three-dimensional structure of ß-tubulin and suggest that the cross-linking of two vicinal cysteine residues (Cys-12 and Cys-213) by trivalent arsenic inactivates the GTP binding site. Furthermore, exogenous GTP can prevent As2O3-induced mitotic arrest.




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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
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Copyright © 1999 by the American Association for Cancer Research.