Cytotoxicity of major tanshinones isolated from Danshen (Salvia miltiorrhiza) on HepG2 cells in relation to glutathione perturbation
Cytotoxicity of major tanshinones isolated from Danshen (Salvia miltiorrhiza) on HepG2 cells in relation to glutathione perturbation
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DOI：
10.1016/j.fct.2007.08.013
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发表时间：
2008-01-01
影响因子：
4.3
通讯作者：
Yeung, J. H. K.
中科院分区：
文献类型：
--
作者：
Lee, W. Y. W.;Chiu, L. C. M.;Yeung, J. H. K.
丹参酮是从丹参（一种治疗心血管疾病的著名中药）的根中分离出的松香烷型二萜醌类化合物。在分离出的主要二萜类化合物中，包括隐丹参酮、丹参酮I、丹参酮IIA和二氢丹参酮，丹参酮IIA已被证明具有多种药理活性，包括抗氧化、预防/治疗心绞痛和心肌梗死以及抗癌特性。丹参酮IIA通常是该草药中含量最丰富的丹参酮，其临床潜力一直是研究的焦点，其中包括其抑制癌细胞系增殖的能力。本研究的目的是研究丹参酮在体外对人HepG2细胞的细胞毒性与细胞内谷胱甘肽扰动（还原型谷胱甘肽，GSH和氧化型谷胱甘肽，GSSG）的关系。使用MTT法的研究表明，所有丹参酮都以浓度依赖的方式降低HepG2细胞的活力，在处理24小时和48小时后，细胞活力分别降低到60%和35%。通过流式细胞术对具有碎片化DNA的凋亡细胞进行评估表明，只有丹参酮IIA（12.5和25μM）诱导癌细胞凋亡。丹参酮IIA和隐丹参酮在处理24小时后分别使G₁细胞显著减少23%和13%。G₁细胞的减少由G₂/M（丹参酮IIA为15%）和S细胞（丹参酮IIA和隐丹参酮分别为8%和13%）的增加所补偿。除丹参酮IIA外，所有研究的丹参酮在低浓度（1.56和3.13μM）时都提高了GSH/GSSG比值，但在高浓度（6.25 - 25μM）时该比值降低，表明存在氧化应激。综上所述，丹参酮IIA通过凋亡导致HepG2细胞毒性，而不影响氧化应激，而其他丹参酮在诱导HepG2细胞凋亡方面效果较低。（C）2007爱思唯尔有限公司。保留所有权利。
Tanshinones are abietane type-diterpene quitiones isolated from the roots of Radix Salvia miltiorrhiza (Danshen), a well-known traditional Chinese medicine in the treatment of cardiovascular diseases. Among the major diterpenes isolated, including cryptotanshinone, tanshinone I, tanshinone IIA and dihydrotanshinone, tanshinone IIA had been shown to posses various pharmacological activities including antioxidant, protection/prevention from angina pectoris and myocardial infarction, and anticancer properties. Tanshinone IIA, usually the most abundant tanshinone present in the herb, has been the focus of studies in its clinical potential, among which its ability to inhibit the proliferation of cancer cell lines. The aim of this study was to study the cytotoxicity of the tanshinones on human HepG2 cells in vitro in relation to intracellular glutathione perturbation (reduced glutathione, GSH and oxidized glutathione, GSSG). Studies using MTT assay showed that all tanshinones decreased cell viability of HepG2 cells in a concentration-dependent manner, with the cell viability decreased to 60% and 35% after 24 h and 48 h treatment, respectively. Assessment of apoptotic cells with fragmented DNA by flow cytometry indicated that only tanshinone IIA (12.5 and 25 mu M) induced apoptosis in the cancer cells. Tanshinone IIA and cryptotanshinone caused significant decreases in G, cells by 23% and 13%, respectively, after 24 h treatment. The declines in G(1) cells were compensated by increases in G(2)/M (15% for tanshinone IIA) and S cells (8% and 13% for tanshinone IIA and cryptotanshinone, respectively). All the tanshinones studied, except tanshinone IIA, elevated GSH/GSSG ratio at low concentrations (1.56 and 3.13 mu M), but the ratio decreased, indicating oxidative stress at high concentrations (6.25-25 mu M). Taken together, tanshinone IIA caused HepG2 cytotoxicity through apoptosis without influencing oxidative stress, while the other tanshinones showed lower efficacy in inducing apoptosis in the HepG2 cells. (C) 2007 Elsevier Ltd. All rights reserved.