Cyclopamine induces eosinophilic differentiation and upregulates CD44 expression in myeloid leukemia cells.
Cyclopamine, a plant-derived steroidal alkaloid, inhibits the hedgehog (Hh) signaling pathway by antagonizing Smoothened. This drug can induce the differentiation of myeloid leukemia cell lines and acute myeloid leukemia (AML) cells in primary culture. The treated cells were stained with Luxol-fast-blue, which is specific for eosinophilic granules. Ligation of CD44 with some specific monoclonal antibodies can reverse the differentiation of AML cells. Combined treatment with cyclopamine and a monoclonal antibody to ligate CD44 more than additively induced the differentiation of HL-60 cells. These results may provide useful information for the development of a CD44-targeted therapy in AML.
Takahashi
Tsutomu
T
Department of Life Science, Shimane University School of Medicine, 89-1 Enya, Izumo, Shimane 693-8501, Japan.
Kawakami
Koshi
K
Mishima
Seiji
S
Akimoto
Miho
M
Takenaga
Keizo
K
Suzumiya
Junji
J
Honma
Yoshio
Y
D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004804:Eosinophils / Q000187:drug effects* / Q000502:physiology; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D007951:Leukemia, Myeloid / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects; D014704:Veratrum Alkaloids / Q000008:administration & dosage / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D014704:Veratrum Alkaloids; C000541:cyclopamine