HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

3-Hydrogenkwadaphnine, a novel diterpene ester from Dendrostellera lessertii, its role in differentiation and apoptosis of KG1 cells.

Abstract
3-Hydrogenkwadaphnin (3-HK) (Fig. 1) is a daphnane-type diterpene ester isolated from the leaves of Dendrostellera lessertii (Thymelaeaceae) with differentiation and apoptotic potency among several leukemic cells without any measurable adverse effects on normal cells [Moosavi, M.A., Yazdanparast, R., Sanati, M.H., Nejad, A.S., 2005a. 3-Hydrogenkwadaphnin targets inosine 5'-monophosphate dehydrogenase and triggers post-G1 arrest apoptosis in human leukemia cell lines. Int. J. Biochem. Cell Biol. 37, 2366-2379]. In this study, we evaluated differentiating and apoptotic efficiency of a second new anti-proliferating agent from the same plant relative to 3-HK using acute myeloid leukemia (AML) KG1 cell line. 3-HK at 5-30 nM inhibited proliferation of KG1 cells after 24-96 h of treatment. NBT reducing assay and expression of cell surface markers (CD11b and CD14) confirmed that the inhibition of proliferation is associated with differentiation toward macrophage-like morphology. Regarding the relatively weaker potency of 3-HK in the induction of differentiation compared to that of the crude extract, we looked for additional compound(s) with similar properties in the crude extract. This effort led to isolation of the second compound from the leaves' extract with higher differentiating potency. The new compound inhibited proliferation of KG1 cells by almost 48+/-3.1% after 72 h of treatment with a single dose of 1.5 microg/ml. The treated cells differentiated along the monocyte/macrophage lineage based on the morphological features apparent after Wright-Giemsa staining, phagocytic activity and expression of cell surface markers as analyzed by flow cytometry. On the other hand, the results indicated that exposure of KG1 cells to either 3-HK or the new compound for 3-4 days induced apoptosis as assayed qualitatively by acridine orange/ethidium bromide (Ao/EtBr) double staining, agarose gel electrophoresis and quantitatively by Annexin-V technique and sub-G1 DNA staining using flow cytometry. Based on the present data, these two active constituents of D. lessertii have the novelty of being further evaluated for pharmaceutical applications.
AuthorsRazieh Yazdanparast, Azadeh Meshkini
JournalPhytomedicine : international journal of phytotherapy and phytopharmacology (Phytomedicine) Vol. 16 Issue 2-3 Pg. 206-14 (Mar 2009) ISSN: 1618-095X [Electronic] Germany
PMID18829278 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • 3-hydrogenkwadaphnin
  • Antineoplastic Agents, Phytogenic
  • Diterpenes
  • Esters
Topics
  • Antineoplastic Agents, Phytogenic (pharmacology, therapeutic use)
  • Apoptosis (drug effects)
  • Cell Differentiation (drug effects)
  • Cell Line, Tumor
  • Cell Proliferation (drug effects)
  • Cell Survival (drug effects)
  • Diterpenes (pharmacology, therapeutic use)
  • Esters (pharmacology)
  • Humans
  • Leukemia (drug therapy)
  • Macrophages
  • Monocytes
  • Phytotherapy
  • Thymelaeaceae

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: