School of Life Sciences, Shanxi University, Taiyuan, Shanxi, China.
College of Horticulture, Shanxi Agricultural University, Taigu, China.
Anticancer Agents Med Chem. 2021;21(1):61-70. doi: 10.2174/1871520620666200708104559.
Periplogenin (PPG), a natural compound isolated from traditional Chinese herb Cortex Periplocae, has been reported to possess anti-inflammatory and anti-cancer properties.
The present study aims to investigate the antitumor effects of PPG and the underlying mechanism in human colorectal cancer cells.
The inhibition of cell growth in vitro was assessed by MTT assay. The induction of apoptosis and the ROS production induced by PPG was investigated by flow cytometry analysis. Western blotting was applied to measure the protein expression. Small interference RNA (siRNA) and a specific pharmacological inhibitor were used to knock down or inhibit the expression of related genes.
PPG was able to cause the production of ROS, inhibit the cancer cell growth and induce apoptosis. Nacetylcysteine was able to inhibit ROS production and apoptosis. PPG up-regulated the protein levels of BIP, peIF2α and CHOP as well as IRE1α and p-JNK, and down-regulated the protein level of p-ASK1, all of which were reversed by N-acetylcysteine. Importantly, knockdown of CHOP or JNK protein level attenuated the PPGelicited apoptosis.
PPG-induced apoptosis was regulated by ROS-mediated BIP/eIF2α/CHOP and BIP/ASK1/JNK signaling pathways in colon cancer cells, suggesting that PPG is a promising therapeutic agent for the treatment of human colon cancer.
从传统中药杠柳皮中分离得到的天然化合物杠柳苷元（PPG）已被报道具有抗炎和抗癌特性。
本研究旨在探讨 PPG 在人结直肠癌细胞中的抗肿瘤作用及其机制。
通过 MTT 法评估体外细胞生长抑制。通过流式细胞术分析检测 PPG 诱导的细胞凋亡和 ROS 产生。Western blot 用于测量蛋白表达。采用小干扰 RNA（siRNA）和特定的药理学抑制剂敲低或抑制相关基因的表达。
PPG 能引起 ROS 产生，抑制癌细胞生长并诱导细胞凋亡。N-乙酰半胱氨酸可抑制 ROS 产生和细胞凋亡。PPG 上调 BIP、peIF2α 和 CHOP 以及 IRE1α 和 p-JNK 的蛋白水平，并下调 p-ASK1 的蛋白水平，这些均被 N-乙酰半胱氨酸逆转。重要的是，CHOP 或 JNK 蛋白水平的敲低减弱了 PPG 诱导的细胞凋亡。
PPG 诱导的细胞凋亡是通过 ROS 介导的 BIP/eIF2α/CHOP 和 BIP/ASK1/JNK 信号通路调节的，提示 PPG 是治疗人类结肠癌的一种有前途的治疗剂。
