Effects of guggulsterone on proliferation and apoptosis of HepG2 human hepatocellular carcinoma cells
-
摘要:
目的研究没药甾酮对人肝癌细胞HepG2增殖和凋亡的影响。方法以正常人肝细胞L-02作为对照,采用3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐法观察不同浓度没药甾酮(5~100μmol/L)对人肝癌细胞HepG2和L-02细胞增殖的影响并观察细胞形态的变化;应用流式细胞术检测细胞周期变化和凋亡发生。结果不同浓度没药甾酮均可显著抑制人肝癌细胞HepG2生长,并呈时间、剂量依赖性,最大抑制率可达81.9%±1.92%(100μmol/L);没药甾酮可使G0/G1期细胞比例增多,G2/M期细胞比例下降,可将细胞阻滞于G0/G1期;没药甾酮诱导人肝癌细胞HepG2发生凋亡,50μmol/L和75μmol/L没药甾酮早期细胞凋亡率分别为24.91%±2.41%、53.03%±2.28%,与对照组相比,差异均具有统计学意义(P<0.05)。结论没药甾酮可抑制人肝癌细胞HepG2增殖并诱导凋亡,其作用可能与干扰细胞周期有关。
Abstract:Objective To investigate the potential therapeutic effects of the plant-derived polyphenol, guggulsterone, on cell proliferation and apoptosis of hepatocellular carcinoma (HCC) by using an in vitro system with the human hepatoma cell line, HepG2.Methods HepG2 cells and normal human liver L-02 cells were treated with different concentrations of guggulsterone (5-100 μmol/L) for 24-72 hours.Differential effects on cell proliferation were tested by MTT assay and on cell cycle and apoptosis were detected by flow cytometry (FACS) .Results Guggulsterone significantly inhibited HepG2 cell proliferation in a dose-and time-dependent manner, with the maximal inhibition effect being observed with 100 μmol/L guggulsterone (81.9%±1.92%) .FACS analysis indicated that guggulsterone-treated HepG2 cells were arrested in the G0/G1 phase.Guggulsterone also induced apoptosis of HepG2 cells (apoptotic %: 50 μmol/L, 24.91±2.41 and 75 μmol/L, 53.03±2.28) .Conclusion Guggulsterone exerts anticancer effects on HepG2 hepatoma cells by inhibiting cell proliferation and inducing apoptosis.The anti-proliferative effect may be related to interference of the cell cycle.
-
Key words:
- commiphora /
- carcinoma /
- hepatocellular /
- cell proliferation /
- apoptosis
-
[1]Meselhy MR.Inhibition of LPS-induced NO production by theoleogum resin of Commiphora wightti and its constituents[J].Phy-tochemistry, 2003, 62 (2) :213-218. [2]Yang DF, Yang J, Shi DS, et al.Hypolipidemic agent Z-guggul-stersone:metabolism interplays with induction of carboxylesteraseand bile salt export pump[J].J Lipid Res, 2012, 53 (3) :529-539. [3]Dufer M, Horth K, Wagner R, et al.Bile acids acutely stimulateinsulin secretion of mouse beta-cells via farnesoid X receptor acti-vation and K-ATP channel inhibition[J].Diabetes, 2012, 61 (6) :1479-1489. [4]Song JJ, Kwon SK, Cho CG, et al.Guggulsterone suppresses LPSinduced inflammation of human middle ear epithelial cells (HMEEC) [J].Int J Pediat Otorhinolaryngol, 2010, 74 (12) :1384-1387. [5]Lee JY, Lee KT, Lee JK, et al.Farnesoid X receptor, overex-pressed in pancreatic cancer with lymph node metastasis promotescell migration and invasion[J].Br J Cancer, 2011, 104 (6) :1027-1037. [6]Shishodia S, Sethi G, Ahn KS, et al.Guggulsterone inhibits tumorcell proliferation, induces S-phase arrest, and promotes apoptosisthrough activation of c-Jun N-terminal kinase, suppression of Aktpathway, and downregulation of antiapoptotic gene products[J].Biochem Phamacol, 2007, 74 (1) :118-130. [7]Macha MA, Matta A, Chauhan SS, et al.Guggulsteron (GS) Inhibitssmokeless tobacco and nicotine-induced NF-kappa B and STAT3pathways in head and neck cancer cells[J].Carcinogenesis, 2011, 32 (3) :368-380. [8] Parkin DM, Bray F, Ferlay J, et al.Global cancer statistics, 2002[J].CA Cancer J Clin, 2005, 55 (2) :74-108. [9]Chen JG.Trends in the incidence of liver cancer and its primaryprevention in China[J].J Clin Hepatol, 2012, 28 (4) :256-260. (in Chinese) 陈建国.中国肝癌发病趋势和一级预防[J].临床肝胆病杂志, 2012, 28 (4) :256-260. [10]Min JA, Jae HC, Seung WK, et al.Guggulsterone induces apopto-sis in colon cancer cells and inhibits tumor growth in murine colorec-tal cancer xenografts[J].Cancer Lett, 2009, 279 (1) :93-100. [11]Hannun YA.Apoptosis and the dilemma of cancer chemotherapy[J].Blood, 1997, 89:1845-1853. [12]Macha MA, Matta A, Chauhan S, et al.14-3-3 zeta is a molec-ular target in guggulsterone induced apoptosis in Head and Neckcancer cells[J].BMC Cancer, 2010, 30 (10) :655-667. [13]Leeman-Neill RJ, Wheeler SE, Singh SV, et al.Guggulsteroneenhances head and neck cancer therapies via inhibition of signaltransducer and activator of transcription-3[J].Carcinogenesis, 2009, 30 (11) :1848-1856. [14]Dang SS.Collection of common experimental technigues in medicine[M].Xi'an:World Book Publishing Company, 2004:270-271. (in Chinese) 党双锁.医学常用实验技术精编[M].西安:世界图书出版社, 2004:270-271.
计量
- 文章访问数: 3012
- HTML全文浏览量: 10
- PDF下载量: 626
- 被引次数: 0