Department of Pathology, College of Oriental Medicine and Research Institute of Oriental Medicine, Dongeui University, Busan 614-052, Republic of Korea.
Int J Oncol. 2012 Jun;40(6):1929-40. doi: 10.3892/ijo.2012.1386. Epub 2012 Feb 22.
The root of Mori cortex has traditionally been used in Korea for the treatment of cutaneous inflammation, pulmonary asthma, and congestion for thousands of years. The present study was designed to validate the anticancer effects of methylene chloride extracts of the M. cortex root (MEMC) in NCI-H460 human lung carcinoma cells. Exposure to MEMC was found to result in growth inhibition by the induction of caspase‑dependent apoptosis in NCI-H460 cells, which correlated with upregulated expression of death receptor (DR)4, DR5 and FasL, downregulation of anti-apoptotic Bcl-2 and Bcl-xL expression, cleavage of Bid, and loss of mitochondrial membrane potential. In addition, autophagosomes, a characteristic finding of autophagy, and markers of autophagy, conversion of microtubule-associated protein light chain-3 (LC3)-I to LC3-II and increased beclin-1 accumulation, were observed in MEMC-treated NCI-H460 cells. Inhibition of autophagy by 3-methyladenine or LC3B small interfering (siRNA) resulted in enhanced apoptotic cell death, suggesting that MEMC-induced autophagy functions as a suppressor of apoptosis. MEMC-induced autophagy was also blocked by N-acetyl-cysteine (NAC) and catalase, indicating that H2O2 can regulate autophagy. Our data demonstrate that MEMC triggers both ROS-mediated autophagy and caspase-dependent apoptosis, and that autophagy plays a protective role against apoptotic cell death.
桑白皮在韩国传统上被用于治疗皮肤炎症、哮喘和充血已有数千年的历史。本研究旨在验证桑白皮甲叉氯（MEMC）提取物对 NCI-H460 人肺癌细胞的抗癌作用。结果发现，MEMC 暴露会导致 NCI-H460 细胞中 caspase 依赖性凋亡的诱导，从而导致细胞生长抑制，这与死亡受体（DR）4、DR5 和 FasL 的上调表达、抗凋亡 Bcl-2 和 Bcl-xL 表达的下调、Bid 的切割以及线粒体膜电位的丧失有关。此外，在 MEMC 处理的 NCI-H460 细胞中观察到自噬的特征发现自噬体和自噬标志物，微管相关蛋白轻链-3（LC3）-I 向 LC3-II 的转化以及 beclin-1 积累的增加。3-甲基腺嘌呤或 LC3B 小干扰（siRNA）抑制自噬会导致凋亡细胞死亡增加，表明 MEMC 诱导的自噬作为凋亡的抑制剂发挥作用。N-乙酰半胱氨酸（NAC）和过氧化氢酶也阻断了 MEMC 诱导的自噬，表明 H2O2 可以调节自噬。我们的数据表明，MEMC 触发 ROS 介导的自噬和 caspase 依赖性凋亡，并且自噬对凋亡细胞死亡起保护作用。
