Wu Shu-Jing, Ng Lean-Teik, Chen Ching-Hsein, Lin Doung-Liang, Wang Shyh-Shyan, Lin Chun-Ching
Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 807, Taiwan, ROC.
Life Sci. 2004 Mar 5;74(16):2061-73. doi: 10.1016/j.lfs.2003.09.058.
Physalis angulata and P. peruviana are herbs widely used in folk medicine. In this study, the aqueous and ethanol extracts prepared from the whole plant of these species were evaluated for their antihepatoma activity. Using XTT assay, three human hepatoma cells, namely Hep G2, Hep 3B and PLC/PRF/5 were tested. The results showed that ethanol extract of P. peruviana (EEPP) possessed the lowest IC50 value against the Hep G2 cells. Interestingly, all extracts showed no cytotoxic effect on normal mouse liver cells. Treatment with carbonyl cyanide m-chlorophenyl hydrazone, a protonophore, caused a reduction of membrane potential (Deltapsim) by mitochondrial membrane depolarization. At high concentrations, EEPP was shown to induce cell cycle arrest and apoptosis through mitochondrial dysfunction as demonstrated by the following observations: (i) EEPP induced the collapse of Deltapsim and the depletion of glutathione content in a dose dependent manner; (ii) pretreatment with the antioxidant (1.0 microg/ml vitamin E) protected cells from EEPP-induced release of ROS; and (iii) at concentrations 10 to 50 microg/ml, EEPP displayed a dose-dependent accumulation of the Sub-G1 peak (hypoploid) and caused G0/G1-phase arrest. Apoptosis was elicited when the cells were treated with 50 microg/ml EEPP as characterized by the appearance of phosphatidylserine on the outer surface of the plasma membrane. The results conclude that EEPP possesses potent antihepatoma activity and its effect on apoptosis is associated with mitochondrial dysfunction.
酸浆和灯笼果是民间医学中广泛使用的草药。在本研究中，对这些物种全株制备的水提取物和乙醇提取物的抗肝癌活性进行了评估。使用XTT法，对三种人肝癌细胞，即Hep G2、Hep 3B和PLC/PRF/5进行了测试。结果表明，灯笼果乙醇提取物（EEPP）对Hep G2细胞的IC50值最低。有趣的是，所有提取物对正常小鼠肝细胞均无细胞毒性作用。用质子载体间氯苯腙处理导致线粒体膜去极化，从而降低膜电位（Δψm）。在高浓度下，EEPP通过线粒体功能障碍诱导细胞周期停滞和凋亡，如下观察结果所示：（i）EEPP以剂量依赖的方式诱导Δψm的崩溃和谷胱甘肽含量的消耗；（ii）用抗氧化剂（1.0μg/ml维生素E）预处理可保护细胞免受EEPP诱导的ROS释放；（iii）在10至50μg/ml的浓度下，EEPP显示出亚G1峰（亚二倍体）的剂量依赖性积累，并导致G0/G1期停滞。当细胞用50μg/ml EEPP处理时，会引发凋亡，其特征是质膜外表面出现磷脂酰丝氨酸。结果表明，EEPP具有强大的抗肝癌活性，其对凋亡的作用与线粒体功能障碍有关。
