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Title: Characterizing the mechanism for ginsenoside-induced cytotoxicity in cultured leukemia (THP-1) cells
Authors: Kitts, D.D.
Popovich, D.G. 
Hu, C.
Keywords: Apoptosis
Cell membrane
Ginseng leaf
Issue Date: Nov-2007
Citation: Kitts, D.D., Popovich, D.G., Hu, C. (2007-11). Characterizing the mechanism for ginsenoside-induced cytotoxicity in cultured leukemia (THP-1) cells. Canadian Journal of Physiology and Pharmacology 85 (11) : 1173-1183. ScholarBank@NUS Repository.
Abstract: 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 ≤ 0.05) increased apoptosis (18% ± 0.4%) after 23 h at a concentration that inhibited cell viability by 50% (LC50 (72 h) = 52 μmg/mL. In comparison, a similar significant (p ≤ 0.05) increase in apoptotic cell numbers occurred at 41 h of exposure for pure ginsenoside standards, PD (LC50 (72 h) = 13 μg/mL), PT (LC50 (72 h) = 19 μg/mL), and Rh2 (LC 50 (72 h) = 15 μg/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 ≤ 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. © 2007 NRC.
Source Title: Canadian Journal of Physiology and Pharmacology
ISSN: 00084212
DOI: 10.1139/Y07-099
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