Journal
LEUKEMIA RESEARCH
Volume 32, Issue 9, Pages 1366-1373Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.leukres.2008.01.019
Keywords
cucurbitacin; leukemia; myelodysplastic syndrome; actin cytoskeleton
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Cucurbitacins have long been utilized for their abortifacient and anti-inflammatory effects; however, little is known about their mechanism of action. In this study, we have demonstrated robust antiproliferative effects of CuB on various leukemia and lymphoma cell lines, as well as on primary mononuclear bone marrow cells derived from patients with acute myeloid leukemia or myelodysplastic syndrome. Myeloid leukemic cells treated with CuB exhibit significant S-phase cell cycle arrest, enlarged cell size, multi nucleation, and enhanced expression of a monocytic-and granulocytic-specific CD11b. Moreover, our data demonstrate that CuB prominently alters the cytoskeletal network of leukemic cells, inducing rapid and improper polymerization of the F-actin network. These encouraging results suggest the appropriateness of clinical trials of cucurbitacins for the treatment of hematopoietic malignancies. (C) 2008 Elsevier Ltd. All rights reserved.
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