Inhibitory mechanism of quercetin and its metabolites on the growth of human hepatoma cells Hep 3B and the effects of quercetun on glutathione-related detoxification and antioxidation system of primary rat hepatocytes
Date Issued
2005
Date
2005
Author(s)
Lee, Yen-Lin
DOI
zh-TW
Abstract
In this study, quercetin and quercetin metabolites, quercetin glucuronides and quercetin sulfates, were used to investigate the anti-proliferation effects and mechanism on human hepatoma cells Hep 3B and the effect on glutathione-related detoxification and antioxidation system of primary rat hepatocytes. We found that after 48 hr treatment, quercetin inhibited the growth of Hep 3B cells and the IC50 value was 335 μM. With much lower IC50 values, two samples containing different amount of quercetin glucuronides and quercetin sulfates showed stronger anti-proliferative effect than quercetin. The IC50 value of sample 1 was 12 μM and sample 2 was 67 μM. Through cell cycle and Western blot analysis, we found that quercetin metabolites arrested Hep 3B cells in G2/M phase while quercetin induced apoptosis of Hep 3B cells by increasing the levels of pro-apoptotic proteins Bax and Bad, decreasing the levels of anti-apoptotic protein Bcl-2, and inducing the cleavages of caspase-3, caspase-9 and PARP. The results of quercetin on glutathione-related detoxification and antioxidation system of primary rat hepatocytes showd that 80 μM quercetin significantly elevated the level of glutathione up to 150 % and increased the activities of glutathione peroxidase to 147 %, glutathione reductase to 141 % and glutathione S-transferase to 115 % as compared with control group (P＜0.05) without causing lipid peroxidation. Quercetin also protected primary rat hepatocytes from 10 mM carbon tetrachloride-induced cytotoxity. The results suggest that quercetin could inhibit the gowth of hepatoma cells, promote the antioxidant defense system and metabolic activity of hepatocytes, and might be a promising agent for the treatment and prevention of human hepatoma.
Subjects
槲皮酮
槲皮酮代謝產物
人類肝癌細胞Hep 3B
大鼠初代肝細胞
麩胱甘肽
quercetin
quercetin metabolites
human hepatoma cells Hep 3B
primary rat hepatocytes
glutathione
Type
thesis
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