Supercritical Carbon Dioxide Extraction of Aromatic Turmerone from Curcuma longa Linn. Induces Apoptosis through Reactive Oxygen Species-Triggered Intrinsic and Extrinsic Pathways in Human Hepatocellu
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- 作者：Shao-Bin Cheng ; Li-Chen Wu ; Yun-Chih Hsieh ; Chi-Hao Wu ; Yu-Ju Chan ; Li-Hsun Chang ; Chieh-Ming J. Chang ; Shih-Lan Hsu ; Chieh-Lin Teng ; Chun-Chi Wu
- 刊名：Journal of Agricultural and Food Chemistry
- 出版年：2012
- 出版时间：September 26, 2012
- 年：2012
- 卷：60
- 期：38
- 页码：9620-9630
- 全文大小：615K
- 年卷期：v.60,no.38(September 26, 2012)
- ISSN：1520-5118
文摘
The mechanisms underlying the antiproliferative and antitumor activities of aromatic turmerone (ar-turmerone), a volatile turmeric oil isolated from Curcuma longa Linn., have been largely unknown. In this study, 86% pure ar-turmerone was extracted by supercritical carbon dioxide and liquid鈥搒olid chromatography and its potential effects and molecular mechanisms on cell proliferation studied in human hepatocellular carcinoma cell lines. Ar-turmerone exhibited significant antiproliferative activity, with 50% inhibitory concentrations of 64.8 卤 7.1, 102.5 卤 11.5, and 122.2 卤 7.6 渭g/mL against HepG2, Huh-7, and Hep3B cells, respectively. Ar-turmerone-induced apoptosis, confirmed by increased annexin V binding and DNA fragmentation, was accompanied by reactive oxygen species (ROS) production, mitochondrial membrane potential dissipation, increased Bax and p53 up-regulated modulator of apoptosis (PUMA) levels, Bax mitochondrial translocation, cytochrome c release, Fas and death receptor 4 (DR4) augmentation, and caspase-3, -8, and -9 activation. Exposure to caspase inhibitors, Fas-antagonistic antibody, DR4 antagonist, and furosemide (a blocker of Bax translocation) effectively abolished ar-turmerone-triggered apoptosis. Moreover, ar-turmerone stimulated c-Jun N-terminal kinase (JNK) and extracellular signal-related kinase (ERK) phosphorylation and activation; treatment with JNK and ERK inhibitors markedly reduced PUMA, Bax, Fas, and DR4 levels and reduced apoptosis but not ROS generation. Furthermore, antioxidants attenuated ar-turmerone-mediated ROS production; mitochondrial dysfunction; JNK and ERK activation; PUMA, Bax, Fas, and DR4 expression; and apoptosis. Taken together, these results suggest that ar-turmerone-induced apoptosis in HepG2 cells is through ROS-mediated activation of ERK and JNK kinases and triggers both intrinsic and extrinsic caspase activation, leading to apoptosis. On the basis of these observations, ar-turmerone deserves further investigation as a natural anticancer and cancer-preventive agent.