Kang Ning, Jian Jun-Feng, Cao Shi-Jie, Zhang Qiang, Mao Yi-Wei, Huang Yi-Yuan, Peng Yan-Fei, Qiu Feng, Gao Xiu-Mei
School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, 312 Anshanxi Road, Nankai District, Tianjin, 300193, People's Republic of China.
Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 312 Anshanxi Road, Nankai District, Tianjin, 300193, People's Republic of China.
Mol Cell Biochem. 2016 Apr;415(1-2):145-55. doi: 10.1007/s11010-016-2686-1. Epub 2016 Mar 21.
Physalin A (PA) is an active withanolide isolated from Physalis alkekengi var. franchetii, a traditional Chinese herbal medicine named Jindenglong, which has long been used for the treatment of sore throat, hepatitis, and tumors in China. In the present study, we firstly investigated the effects of PA on proliferation and cell cycle distribution of the human non-small cell lung cancer (NSCLC) A549 cell line, and the potential mechanisms involved. Here, PA inhibited cell growth in dose- and time-dependent manners. Treatment of A549 cells with 28.4 μM PA for 24 h resulted in approximately 50 % cell death. PA increased the amount of intracellular ROS and the proportion of cells in G2/M. G2/M arrest was attenuated by the addition of ROS scavenger NAC. ERK and P38 were triggered by PA through phosphorylation in a time-dependent manner. The phosphorylation of ERK and P38 were not attenuated by the addition of NAC, but the use of the p38 inhibitor could reduce, at least in part, PA-induced ROS and the proportion of cells in G2/M. PA induces G2/M cell cycle arrest in A549 cells involving in the p38 MAPK/ROS pathway. This study suggests that PA might be a promising therapeutic agent against NSCLC.
酸浆苦素A(PA)是从酸浆(一种名为锦灯笼的传统中草药)中分离出的一种活性醉茄内酯,在中国长期用于治疗咽喉痛、肝炎和肿瘤。在本研究中,我们首先研究了PA对人非小细胞肺癌(NSCLC)A549细胞系增殖和细胞周期分布的影响及其潜在机制。在此,PA以剂量和时间依赖性方式抑制细胞生长。用28.4 μM PA处理A549细胞24小时导致约50%的细胞死亡。PA增加了细胞内活性氧(ROS)的含量以及G2/M期细胞的比例。添加ROS清除剂NAC可减弱G2/M期阻滞。PA以时间依赖性方式通过磷酸化激活ERK和P38。添加NAC并未减弱ERK和P38的磷酸化,但使用p38抑制剂可至少部分降低PA诱导的ROS以及G2/M期细胞的比例。PA通过p38丝裂原活化蛋白激酶/ROS途径诱导A549细胞发生G2/M期细胞周期阻滞。本研究表明,PA可能是一种有前景的抗NSCLC治疗药物。