Document Detail


Pro-oxidant and cytotoxic activities of atractylenolide I in human promyeloleukemic HL-60 cells.
MedLine Citation:
PMID:  16624472     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The dried rhizome of Bai Zhu (Atractylodes ovata) is widely used as a Chinese herbal medicine. Two sesquiterpenolides of similar structures (atractylenolide I, AT-I; atractylenolide III, AT-III) were isolated from dried rhizome of Atractylodes ovata. Incubation of AT-I with recombinant human Cu,Zn-superoxide dismutase (rhCu,Zn-SOD) resulted in rhCu,Zn-SOD fragmentations and Zn releases. However, these were not observed in the AT-III reaction. The AT-1 showed dose-dependent cytotoxic activities (7.5, 15, and 30 microg/ml) on the human promyeloleukemic HL-60 cells while AT-III did not, and the IC50 of the former being 10.6 microg/ml (corresponding to 46 microM) on 12 h-treated cells. The results of DNA ladder and DNA contents in sub-G1 type revealed that AT-I induced apoptosis in human promyeloleukemic HL-60 cells. The cytotoxic and pharmacological mechanisms of AT-I against human promyeloleukemic HL-60 cells was investigated. The AT-I appeared to exhibit both pro-oxidant and antioxidant properties after an ESR spectrometer was used to detect hydroxyl radical productions in vitro and flow cytometry to detect intracellular ROS productions in AT-I treated cells. The AT-1 also showed dose-dependent Cu,Zn-SOD inhibitory activity in HL-60 cells treated for 12 h, confirmed by activity and immune stainings. However, catalase, Mn-SOD, and glutathione peroxidase did not apparently change activities under the same treatments. The addition of commercial rhCu,Zn-SOD (25-100 U/mL) to the AT-I-treated HL-60 cells (15 microg/ml) resulted in significant differences (p<0.01) and could reduce the AT-I cytotoxicity from 78% to 28% on HL-60 cells. It was proposed that the AT-I might work via Cu,Zn-SOD inhibition in HL-60 cells to induce apoptosis and bring about cytotoxicity.
Authors:
Ching-Chiung Wang; Shyr-Yi Lin; Huey-Chuan Cheng; Wen-Chi Hou
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-02-28
Journal Detail:
Title:  Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association     Volume:  44     ISSN:  0278-6915     ISO Abbreviation:  Food Chem. Toxicol.     Publication Date:  2006 Aug 
Date Detail:
Created Date:  2006-06-23     Completed Date:  2006-09-19     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8207483     Medline TA:  Food Chem Toxicol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1308-15     Citation Subset:  IM    
Affiliation:
Graduate Institute of Pharmacognosy, Taipei Medical University Hospital, No. 250, Wu-Hsing Street, Taipei 110, Taiwan.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / drug effects
Asteraceae / chemistry*
Cell Survival / drug effects,  physiology
DNA Fragmentation / drug effects,  physiology
Drug Interactions
Electron Spin Resonance Spectroscopy
Flow Cytometry
Free Radical Scavengers / pharmacology
HL-60 Cells
Humans
Hydrogen Peroxide
Hydroxyl Radical / metabolism
Inhibitory Concentration 50
Iron
Lactones / pharmacology*
Peroxides / metabolism
Recombinant Proteins / pharmacology
Rhizome / chemistry
Sesquiterpenes / pharmacology*
Superoxide Dismutase / antagonists & inhibitors,  metabolism*,  pharmacology
Zinc / metabolism
Chemical
Reg. No./Substance:
0/Fenton's reagent; 0/Free Radical Scavengers; 0/Lactones; 0/Peroxides; 0/Recombinant Proteins; 0/Sesquiterpenes; 0/atractylenolide I; 0/atractylenolide III; 3352-57-6/Hydroxyl Radical; 7439-89-6/Iron; 7440-66-6/Zinc; 7722-84-1/Hydrogen Peroxide; EC 1.15.1.1/Superoxide Dismutase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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