Cytotoxicity of major tanshinones isolated from Danshen (Salvia miltiorrhiza) on HepG2 cells in relation to glutathione perturbation
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AbstractTanshinones 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.
All Author(s) ListLee WYW, Chiu LCM, Yeung JHK
Journal nameFood and Chemical Toxicology
Year2008
Month1
Day1
Volume Number46
Issue Number1
PublisherPERGAMON-ELSEVIER SCIENCE LTD
Pages328 - 338
ISSN0278-6915
eISSN1873-6351
LanguagesEnglish-United Kingdom
Keywordscryptotanshinone; cytotoxicity; Danshen; dihydrotanshinone; glutathione; GSH/GSSG ratio; HepG2 cells; Salvia miltiorrhiza; tanshinone I; tanshinone IIA
Web of Science Subject CategoriesFood Science & Technology; FOOD SCIENCE & TECHNOLOGY; Toxicology; TOXICOLOGY

Last updated on 2024-23-08 at 00:22