Document Detail


Antiproliferation effects of ponicidin on human myeloid leukemia cells in vitro.
MedLine Citation:
PMID:  15756438     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Ponicidin, an extract from the Chinese herb Rabdosia rubescens, is currently one of the most important traditional Chinese herbal medicines. Ponicidin has been reported to have anti-tumor effects on a large variety of malignant diseases. In this study, we investigated the anti-proliferation effects of ponicidin on human myeloid K562 and HL-60 cells. Cell viability was measured by MTT assay; cell apoptosis was assessed by flow cytometry, DNA fragmentation analysis and Hoechst 33258 staining. Caspase-3 and poly(ADP-ribose) polymerase (PARP) activation and Bax and Bcl-2 expression were detected by Western blot analysis. The results revealed that ponicidin could significantly inhibit the growth of K562 and HL-60 cells by induction of apoptosis. The suppression was both time- and dose-dependent. Cell apoptosis was observed clearly after the cells were treated with ponicidin for 48-72 h. Western blotting showed cleavage of the caspase-3 zymogen protein (32 kDa) with the appearance of its 17 kDa subunit, together with a cleaved 89-kDa fragment of 116 kDa PARP when apoptosis occurred. Bcl-2 expression was down-regulated while Bax expression up-regulated concurrently when the cells were treated with ponicidin for 24-48 h. Therefore, we conclude that ponicidin has significant anti-proliferation effects by induction of apoptosis on myeloid leukemia cells in vitro, down-regulation of Bcl-2, and up-regulation of Bax, and that activation of caspase-3 and PARP may be an important apoptosis-inducing mechanism. The results suggest that ponicidin may serve as a potential therapeutic agent for leukemia.
Authors:
Jia-Jun Liu; Ren-Wei Huang; Dong-Jun Lin; Xiang-Yuan Wu; Qu Lin; Jun Peng; Xianglin Pan; Yu-Qin Song; Mao-Hong Zhang; Ming Hou; Feng Chen
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Oncology reports     Volume:  13     ISSN:  1021-335X     ISO Abbreviation:  Oncol. Rep.     Publication Date:  2005 Apr 
Date Detail:
Created Date:  2005-03-09     Completed Date:  2005-08-26     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  9422756     Medline TA:  Oncol Rep     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  653-7     Citation Subset:  IM    
Affiliation:
Sun Yat-sen University, Department of Haematology and Oncology, The Third Affiliated Hospital of Sun Yat-sen University, Tian-He Road 600, Guangzhou, Guangdong 510630, PR China. liujj@gzsums.edu.cn
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / pharmacology*
Apoptosis
Bisbenzimidazole / pharmacology
Blotting, Western
Caspase 3
Caspases / metabolism
Cell Proliferation
Cell Survival
DNA Fragmentation
Diterpenes / pharmacology*
Dose-Response Relationship, Drug
Down-Regulation
Drugs, Chinese Herbal
Flow Cytometry
HL-60 Cells
Humans
K562 Cells
Leukemia, Myeloid / drug therapy*,  metabolism*
Models, Chemical
Plant Extracts / pharmacology
Poly(ADP-ribose) Polymerases / metabolism
Proto-Oncogene Proteins c-bcl-2 / biosynthesis
Time Factors
Up-Regulation
bcl-2-Associated X Protein
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/BAX protein, human; 0/Diterpenes; 0/Drugs, Chinese Herbal; 0/Plant Extracts; 0/Proto-Oncogene Proteins c-bcl-2; 0/bcl-2-Associated X Protein; 23491-44-3/Bisbenzimidazole; 52617-37-5/ponicidin; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases

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