Cucurbitacin B induces differentiation, cell cycle arrest, and actin cytoskeletal alterations in myeloid leukemia cells.
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, multinucleation, 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.
Haritunians
Talin
T
Division of Hematology/Oncology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. haritunianst@cshs.org
Gueller
Saskia
S
Zhang
Ling
L
Badr
Riem
R
Yin
Dong
D
Xing
Hongtao
H
Fung
Ming Chiu
MC
Koeffler
H Phillip
HP
D000199:Actins / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D039481:CD11b Antigen / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000473:pathology*; D006098:Granulocytes / Q000378:metabolism / Q000473:pathology; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000378:metabolism*; D009190:Myelodysplastic Syndromes / Q000188:drug therapy / Q000473:pathology*; D016196:S Phase / Q000187:drug effects*; D014315:Triterpenes / Q000494:pharmacology*
D000199:Actins; D039481:CD11b Antigen; C509295:ITGAM protein, human; D014315:Triterpenes; C041246:cucurbitacin B