Daphnane diterpene esters isolated from flower buds of Daphne genkwa induce apoptosis in human myelocytic HL-60 cells and suppress tumor growth in Lewis lung carcinoma (LLC)-inoculated mouse model

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Title
Daphnane diterpene esters isolated from flower buds of Daphne genkwa induce apoptosis in human myelocytic HL-60 cells and suppress tumor growth in Lewis lung carcinoma (LLC)-inoculated mouse model
Author(s)
Bo Young Park; B S Min; Kyung Seop AhnOk Kyong Kwon; Hyouk Joung; K H Bae; Hyeong Kyu Lee; Sei Ryang Oh
Bibliographic Citation
Journal of Ethnopharmacology, vol. 111, no. 3, pp. 496-503
Publication Year
2007
Abstract
In this study, two daphnane diterpene esters isolated from the flower buds of Daphne genkwa, genkwadaphnin (1) and yuanhuacine (2), were assessed with regard to their apoptotic activity in human promyelocytic HL-60 cells. Both 1 and 2 were demonstrated to activate the apoptotic process, including DNA fragmentation, chromatin condensation, and sub-G1 hypodiploidy. In our immunoblotting analysis, treatment with compounds 1 and 2 resulted in the cleavage of procaspase-3 and poly(ADP-ribose)polymerase (PARP) into active forms, and the expression of Bcl-2 proteins was shifted toward apoptosis; the expression of the pro-apoptotic protein, Bax, was increased, and the expression of Bcl-2 and Bcl-XL, both anti-apoptotic proteins, were suppressed in a dose-dependent manner. The administration (ip) of the compounds to Lewis lung carcinoma (LLC)-inoculated mice evidenced a significant inhibition of tumor growth (volume), with reductions of 47.9% and 63.1% (1), and 24.2% and 45.8% (2) at concentrations of 0.1 mg/kg and 0.5 mg/kg, as compared with the control mice. These results indicate that compounds 1 and 2 are potent apoptotic constituents of Daphne genkwa, and might be potent as anti-tumoric agents.
Keyword
ApoptosisCaspase-3Daphne genkwaGenkwadaphninYuanhuacine
ISSN
0378-8741
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.jep.2006.12.023
Type
Article
Appears in Collections:
Ochang Branch Institute > Natural Product Research Center > 1. Journal Articles
Ochang Branch Institute > Division of National Bio-Infrastructure > Bio-Resource Central Bank > 1. Journal Articles
Ochang Branch Institute > 1. Journal Articles
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