Shieh Den-En, Chen Yuan-Ying, Yen Ming-Hong, Chiang Lien-Chai, Lin Chun-Ching
Graduate Institute of Pharmaceutical Sciences, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC.
Life Sci. 2004 Mar 19;74(18):2279-90. doi: 10.1016/j.lfs.2003.09.060.
Most of the commonly used cytotoxic anticancer drugs have been shown to induce apoptosis in susceptible cells. However, the signaling pathway of their apoptotic effects remains undefined. In this study, the cytotoxic effect of emodin on various human hepatoma cell lines was investigated. Results demonstrated that emodin exhibited strongly suppressing effect on HepG2/C3A, PLC/PRF/5, and SK-HEP-1 cells, with the IC(50) value of 42.5, 46.6, and 53.1 microM, respectively. Furthermore, emodin induced apoptosis in HepG2/C3A cells was clearly verified by the appearance of DNA fragmentation and sub-G(1) accumulation. Besides, HepG2/C3A cells were found to be arrested in G(2)/M phase after the cells were treated with 60 microM emodin for 48 h. Moreover, significant increase in the levels of apoptosis-related signals such as p53 (419.3 pg/ml), p21 (437.4 units/ml), Fas (6.6 units/ml), and caspase-3 (35.4 pmol/min) were observed in emodin treated HepG2/C3A cells. Taken together, emodin displays effective inhibitory effects on the growth of various human hepatoma cell lines and stimulates the expression of p53 and p21 that resulted in the cell cycle arrest of HepG2/C3A cells at G(2)/M phase. Results also suggest that emodin-induced apoptosis in HepG2/C3A cells were mediated through the activation of p53, p21, Fas/APO-1, and caspase-3. It implies that emodin could be a useful chemotherapeutical agent for treatment of hepatocellular carcinoma (HCC).
大多数常用的细胞毒性抗癌药物已被证明可诱导敏感细胞凋亡。然而，其凋亡作用的信号通路仍不明确。本研究调查了大黄素对各种人肝癌细胞系的细胞毒性作用。结果表明，大黄素对HepG2/C3A、PLC/PRF/5和SK-HEP-1细胞具有强烈的抑制作用，IC(50)值分别为42.5、46.6和53.1 microM。此外，DNA片段化和亚G(1)期积累的出现清楚地证实了大黄素诱导HepG2/C3A细胞凋亡。此外，在用60 microM大黄素处理细胞48小时后，发现HepG2/C3A细胞停滞在G(2)/M期。此外，在大黄素处理的HepG2/C3A细胞中观察到凋亡相关信号如p53（419.3 pg/ml）、p21（437.4单位/ml）、Fas（6.6单位/ml）和caspase-3（35.4 pmol/min）水平显著增加。综上所述，大黄素对各种人肝癌细胞系的生长显示出有效的抑制作用，并刺激p53和p21的表达，导致HepG2/C3A细胞在G(2)/M期停滞。结果还表明，大黄素诱导HepG2/C3A细胞凋亡是通过激活p53、p21、Fas/APO-1和caspase-3介导的。这意味着大黄素可能是一种治疗肝细胞癌（HCC）的有用化疗药物。
