| Summary: | 碩士 === 中國醫藥大學 === 醫學研究所 === 92 === Emodin, an anthraquinone compound isolated from Rheum palmatum L., has been reported to possess anticancer effect on several human cancers such as liver cancers and breast cancers. However, the molecular mechanisms of emodin-mediated tumor regression are not fully defined. In this study, we found that treatment of human lung adenocarcinoma A549 cells with emodin resulted in dose- and time-dependent decrease in cell viability. Moreover, emodin significantly induced apoptosis evidenced by morphological changes, DAPI staining, and TUNEL assay. We also found that emodin resulted in cell cycle S-phase arrest and subsequently progressed to apoptotic cell death. The emodin-induced S-phase arrest was accompanied by downregulation of cyclin A, B and Cdk1, 2 and upregulation of p53, p21CIP1/WAF1/sdi1, and p27KIP1 proteins. Moreover, emodin stimulated the generation of reactive oxygen species (ROS) generation and the Membrance permibility transition （MPT）change. Pretreatment with ascorbic acid significantly blocked the emodin-induced production and apoptosis. In emodin-treated cells, a marked increase of Bax and decrease of Bcl-2 protein in mitochondrial membrance were detected. Overexpression of Bcl-2 by adeno-Bcl-2 virus infection dramatically protected A549 cells against emodin-triggered apoptosis. Furthermore, administration of emodin resulted in the activation of caspases -2,-3, -8, and -9. Cotreatment with the inhibitor of caspases -2, -3, -8, or -9 significantly prevented emodin-mediated apoptotic cell death. We also observed that the ERK, JNK, and AKT kinase activities are decreased. Preincubation with Aurintricarboxylic acid (ATA), an ERK activator, also markedly blocked the emodin-induced apoptosis. Taken together, our observations demonstrated that regulation of the expression levels of cyclin A and B, Cdk1 and 2, p53, p21CIP/WAF1/sdil , and p27KIP1 proteins might involve in emodin-induced S-phase arrest. In addition generation of ROS, down regulation of the ERK and AKT and activation of Bcl-2 family-dependent mitochondrial downstream caspases contributed to apoptosis in emodin-treated adenocarcinoma A549 cells.
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