Anticancer Effects of Imperatorin Isolated from Angelica dahurica: Induction of Apoptosis in HepG2 Cells through both Death-Receptor- and Mitochondria-Mediated Pathways
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摘要Background: Imperatorin (IM) is a furanocoumarin isolated from the root of Angelica dahurica, which is reported to have anticonvulsant and anticancer effects. In this study, the antiproliferative effect of IM on 9 human cancer cell lines was examined, and human hepatoma HepG2 cells were chosen as the target for preferential killing by IM. Particularly, the mechanism of IM-induced apoptosis and in vivo animal effects were also studied. Methods: Cell viability was measured using MTT assay, and apoptosis was detected by Hoechst staining, annexin V-PI staining, and DNA laddering assay. Mitochondrial membrane potential was detected by JC-1 staining. Western blot analysis was employed to detect the expression of apoptosis-related proteins. In addition, the in vivo anticancer effect of IM was examined in nude mice bearing HepG2 cells. Results: IM inhibited the proliferation of HepG2 cells through apoptosis induction in a time-and dose-dependent manner by observation of the nuclear morphology, DNA fragmentation, phosphatidylserine externalization, loss of mitochondrial membrane potential, release of cytochrome c into cytosol, and activation of caspase-3, caspase-8, caspase-9, and poly(ADP-ribose) polymerase cleavage. As cell death could partly be prevented by the caspase-8 or caspase-9 inhibitor and was evidenced by the results of Western blot analysis, our results also suggest that IM-induced apoptosis is mediated through both death receptor and mitochondrial pathways. In the animal model, IM was found to effectively suppress tumor growth by 31.93 and 63.18% at dosages of 50 and 100 mg/kg, respectively, after treatment for 14 days. No significant weight loss or toxicity to the hosts was found. Conclusions: IM can function as a cancer suppressor by inducing apoptosis in HepG2 cells through both death-receptor-and mitochondria-mediated pathways. Furthermore, the in vivo antitumor activities of IM are significant with negligible weight loss and damage to the host. Copyright (C) 2011 S. Karger AG, Basel
著者Luo KW, Sun JG, Chan JYW, Yang L, Wu SH, Fung KP, Liu FY
期刊名稱Chemotherapy
詳細描述To ORKTS: DOI:10.1159/000331641.
出版年份2011
月份1
日期1
卷號57
期次6
出版社KARGER
頁次449 - 459
國際標準期刊號0009-3157
語言英式英語
關鍵詞Anticancer effect; Apoptosis; HepG2; Imperatorin
Web of Science 學科類別Oncology; ONCOLOGY; Pharmacology & Pharmacy; PHARMACOLOGY & PHARMACY

上次更新時間 2021-15-09 於 00:07