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.

References

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