Planta Med 2005; 71(12): 1112-1117
DOI: 10.1055/s-2005-873165
Original Paper
Pharmacology
© Georg Thieme Verlag KG Stuttgart · New York

3-Hydrogenkwadaphnin from Dendrostellera lessertii Induces Differentiation and Apoptosis in HL-60 Cells

Razieh Yazdanparast1 , Mohammad Amin Moosavi1 , Majid Mahdavi1 , Mohammad Hasan Sanati2
  • 1Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran
  • 2National Research Center for Genetic Engineering and Biotechnology, Tehran, Iran
Further Information

Publication History

Received: December 20, 2004

Accepted: June 20, 2005

Publication Date:
10 November 2005 (online)

Abstract

3-Hydrogenkwadaphnin (3-HK) is a new diterpene ester, recently isolated from the leaves of Dendrostellera lessertii with potent anti-tumoral and anti-metastatic activities. Herein, we report that 3-HK induces differentiation and apoptosis in HL-60 cells. The drug at 2.5 - 40 nM inhibited proliferation of HL-60 cells after 24 - 96 h of treatment. Cell viability was also decreased by 57 % after 96 h treatment with the drug. NBT reducing assay and phagocytic activity revealed that the inhibition of proliferation is associated with differentiation especially toward macrophages-like morphology. Indeed, the drug at 2.5 - 10 nM induced differentiation by 5 - 49 % in HL-60 cells. Acridine orange/ethidium bromide (AO/EtBr) double staining and DNA fragmentation assays revealed that apoptosis occurred after differentiation of HL-60 cells. Guanosine at 50 μM decreased the apoptotic cell death and the differentiation caused by the drug. Therefore, GTP depletion, as a result of inhibition of inosine monophosphate dehydrogenase (IMPDH), is considered as one of the main reasons for differentiation and apoptotic cell death by this new drug.

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Dr. R. Yazdanparast

Institute of Biochemistry and Biophysics

P. O. Box 13145-1384

University of Tehran

Tehran

Iran

Phone: +98-21-695-6976

Fax: +98-21-640-4680

Email: yazdan@ibb.ut.ac.ir