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Cotylenin A-induced differentiation is independent of the transforming growth factor-beta signaling system in human myeloid leukemia HL-60 cells.

Abstract
Cotylenin A, which has been isolated as a plant growth regulator, potently induces the differentiation of human myeloid leukemia cells. Treatment of HL-60 cells with a combination of transforming growth factor (TGF)-beta and 1alpha, 25-dihydroxyvitamin D(3) (VD3) resulted in increased differentiation compared to separate treatments, but TGF-beta did not affect the cotylenin A-induced differentiation of HL-60 cells. It is possible that the signal transduction pathway used by cotylenin A for inducing the differentiation of leukemia cells is the same as that used by TGF-beta. However, cotylenin A did not affect the expression of TGF superfamily or Smad genes in HL-60 cells. Treatment with neutralizing anti-TGF-beta antibody or an inhibitor of TGF-beta signaling did not inhibit cotylenin A-induced differentiation, although VD3-induced differentiation was significantly suppressed by these treatments. The subcellular distribution of Smad3 was also unaffected by cotylenin A. These results suggest that the cotylenin A-induced differentiation of leukemia cells is independent of the TGF-beta signaling system, although TGF-beta acts as an autocrine mediator of the growth arrest and differentiation of leukemia cells induced by VD3 and other inducers.
AuthorsManabu Matsunawa, Yuki Ishii, Takashi Kasukabe, Shigeru Tomoyasu, Hidekazu Ota, Yoshio Honma
JournalLeukemia & lymphoma (Leuk Lymphoma) Vol. 47 Issue 4 Pg. 733-40 (Apr 2006) ISSN: 1042-8194 [Print] United States
PMID16690533 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Diterpenes
  • RNA, Messenger
  • Smad3 Protein
  • Transforming Growth Factor beta
  • cotylenin A
Topics
  • Cell Differentiation
  • Cell Line, Tumor
  • Diterpenes (pharmacology)
  • Gene Expression Regulation, Neoplastic
  • HL-60 Cells
  • Humans
  • Immunohistochemistry
  • Leukemia, Myeloid, Acute (drug therapy)
  • Models, Biological
  • RNA, Messenger (metabolism)
  • Signal Transduction
  • Smad3 Protein (metabolism)
  • Transforming Growth Factor beta (metabolism)
  • U937 Cells

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