Phenolic-Containing Organic Extracts of Mulberry (Morus alba L.) Leaves Inhibit HepG2 Hepatoma Cells Through G2/M Phase Arrest, Induction of Apoptosis, and Inhibition of Topoisomerase IIα Activity

被引:83
作者
Naowaratwattana, Wanlaya [2 ]
De-Eknamkul, Wanchai [1 ]
De Mejia, Elvira Gonzalez [3 ]
机构
[1] Chulalongkorn Univ, Fac Pharmaceut Sci, Dept Pharmacognosy, Bangkok 10330, Thailand
[2] Chulalongkorn Univ, Fac Pharmaceut Sci, Dept Biochem, Bangkok 10330, Thailand
[3] Univ Illinois, Dept Food Sci & Human Nutr, Urbana, IL 61801 USA
关键词
antioxidant capacity; apoptosis; cell cycle; chemoprevention; HepG2; cells; Morus alba L; phenolic compounds; topoisomerase II alpha; ANTIOXIDANT; FLAVONOIDS; LIVER; BIOSYNTHESIS; ROLES;
D O I
10.1089/jmf.2010.1021
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
The entire plant of Morus alba L. (Family Moraceae), or mulberry, possesses medical benefits, including anticancer properties. In this study, we investigated the effect of mulberry leaf extracts on the human hepatoma HepG2 cell line, which is related to hepatocellular carcinoma. Mulberry leaf extracts were prepared using four solvents, each with different polarities: 100% methanol (MeOH), 50% aqueous MeOH, 1-butanol (BuOH), and hot water (W). The phenolic profile, total polyphenol content, antioxidant capacity, and effect on human hepatoma HepG2 cells of the leaf extracts were analyzed by examining cytotoxicity, cell cycle progression, apoptosis, expression of topoisomerase II alpha, and proteins involved in cell cycle progression. High-performance liquid chromatography-mass spectrometry analysis revealed that 100% MeOH, 50% MeOH, and BuOH extracts contained rutin, isoquercetin, and various derivatives of kaempferol and quercetin glycosides as their major constituents; the W extract contained primarily chlorogenic acid and caffeoylquinic acid derivatives. Total phenolic content based on rutin equivalents was 17.1%, 9.6%, 8.3%, and 6.5% of dry 100% MeOH, 50% MeOH, BuOH, and W extracts, respectively. 2,2-Diphenyl-1-picrylhydrazyl radical scavenging activities were 70.0%, 45.8%, 41.0%, and 33.6%, and 50% inhibitory concentration values were 33.1, 79.4, 35.6, and 204.2 mu g/mL for HepG2 cell proliferation inhibition for 100% MeOH, 50% MeOH, BuOH, and W extracts, respectively. MeOH extracts caused cell cycle G2/M arrest and induced the caspase cascade and apoptosis, but the W extract had very little effect on cell cycle progression. MeOH extracts reduced the level of topoisomerase II alpha but increased the level of p27(Kip1), with no significant effect on p21(Cip1/waf1). Therefore, we concluded that phenolic-containing organic extracts of mulberry leaves inhibit the growth of HepG2 hepatoma cells through coordinated actions of inducing cell cycle arrest in the G2/M phase (with p27(Kip1) protein expression), inhibiting topoisomerase II alpha activity, and inducing cell apoptosis by activation of caspases.
引用
收藏
页码:1045 / 1056
页数:12
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