Document Detail


Characterizing the mechanism for ginsenoside-induced cytotoxicity in cultured leukemia (THP-1) cells.
MedLine Citation:
PMID:  18066119     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Pure ginsenoside standards (saponins Rh2, PD, and PT), along with an Rh2-enhanced North American ginseng (Panax quinquefolius) leaf extract (LFRh2), were tested for cytotoxic activity in cultured THP-1 leukemia cells. Thermal treatment of ginseng leaf resulted in production of both Rh2 and Rg3 content that was confirmed by liquid chromatography - mass spectrometry (LC-MS). Flow cytometry of cells stained with annexin V - fluorescein isothiocyanate and propidium iodide showed that the LFRh2 significantly (p < or = 0.05) increased apoptosis (18% +/- 0.4%) after 23 h at a concentration that inhibited cell viability by 50% (LC50 (72 h) = 52 microg/mL. In comparison, a similar significant (p < or = 0.05) increase in apoptotic cell numbers occurred at 41 h of exposure for pure ginsenoside standards, PD (LC50 (72 h) = 13 microg/mL), PT (LC50 (72 h) = 19 microg/mL), and Rh2 (LC50 (72 h) = 15 microg/mL). Although no further increase in apoptosis was observed in THP-1 cells after exposure to increasing concentrations of LFRh2 and pure Rh2, PD, and PT standards, a significant (p < 0.05) increase in the percentage of necrotic cells did occur after exposure of cells to different ginsenosides at elevated concentrations. THP-1 caspase-3 activity was greatest (p <or= 0.05) with Rh2 (7.6 +/- 1.1 nmol/L pNA), followed by LFRh2 (5.9 +/- 1.0 nmol/L pNA) and PT (5.0 +/- 0.8 nmol/L pNA), whereas PD was similar to control cells. We define for the first time the proportion of apoptotic to necrotic events that characterize the relative cytotoxicity and reduced cell proliferation of different ginsenosides in cultured THP-1 cells. Moreover, thermal treatment of North American ginseng leaf produced a marked transformation of ginsenoside, largely attributable to an increase in Rh2 content. This change was associated with cytotoxic properties in THP-1 cell that were related to alterations in cell membrane properties, which were also obtained with the pure ginsenosides PD, PT, and Rh2.
Authors:
David D Kitts; David G Popovich; Chun Hu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Canadian journal of physiology and pharmacology     Volume:  85     ISSN:  0008-4212     ISO Abbreviation:  Can. J. Physiol. Pharmacol.     Publication Date:  2007 Nov 
Date Detail:
Created Date:  2007-12-10     Completed Date:  2008-03-19     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372712     Medline TA:  Can J Physiol Pharmacol     Country:  Canada    
Other Details:
Languages:  eng     Pagination:  1173-83     Citation Subset:  IM    
Affiliation:
Food, Nutrition and Health, University of British Columbia, 2205 East Mall, Vancouver, BC V6T 1Z4, Canada. ddkitts@interchange.ubc.ca
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents, Phytogenic / pharmacology*
Cell Line, Tumor
Chromatography, High Pressure Liquid
Flow Cytometry
Ginsenosides / pharmacology*
Humans
L-Lactate Dehydrogenase / secretion
Leukemia, Monocytic, Acute / drug therapy*,  pathology
Panax / chemistry*
Plant Extracts / pharmacology*
Plant Leaves / chemistry
Chemical
Reg. No./Substance:
0/Antineoplastic Agents, Phytogenic; 0/Ginsenosides; 0/Plant Extracts; 78214-33-2/ginsenoside Rh2; EC 1.1.1.27/L-Lactate Dehydrogenase

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


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