Biochemical and Biophysical Research Communications ( IF 2.5 ) Pub Date : 2021-12-01 , DOI: 10.1016/j.bbrc.2021.11.101 Chun-Xiao Wang 1 , Li-Hua Chen 1 , Hai-Bin Zhuang 1 , Ze-Sheng Shi 1 , Zhi Chuan Chen 1 , Jian-Peng Pan 1 , Zhong-Shi Hong 1
Colorectal cancer (CRC) is one of the most common malignant tumors in the digestive system, and Chinese herbal medicine plays an important role in tumor treatment. The in-depth study of auriculasin isolated from Flemingia philippinensis showed that auriculasin promoted reactive oxygen species (ROS) generation in a concentration-dependent manner; when ROS scavenger NAC was added, the effects of auriculasin in promoting ROS generation and inhibiting cell viability were blocked. Auriculasin induced CRC cell apoptosis, led to mitochondrial shrinkage, and increased the intracellular accumulation of Fe2+ and MDA. When auriculasin and NAC were added simultaneously, the levels of apoptosis, Fe2+ and MDA returned to the control group levels, indicating that auriculasin activated apoptosis and ferroptosis by inducing ROS generation. In addition, auriculasin promoted the expression of Keap1 and AIFM1, but significantly reduced the phosphorylation level of AIFM1, while NAC significantly blocked the regulation of Keap1 and AIFM1 by auriculasin, which indicates that auriculasin can also induce oxeiptosis through ROS. When Z-VAD-FMK, Ferrostatin-1, Keap1 siRNA, PGAM5 siRNA and AIFM1 siRNA were added respectively, the inhibitory effect of auriculasin on cell viability was significantly weakened, indicating that auriculasin inhibits cell viability by inducing apoptosis, ferroptosis and oxeiptosis. Auriculasin also inhibited the invasion and clone forming ability of CRC cells, while NAC blocked the above effects of auriculasin. Therefore, auriculasin can promote CRC cell apoptosis, ferroptosis and oxeiptosis by inducing ROS generation, thereby inhibiting cell viability, invasion and clone formation, indicating that auriculasin has a significant antitumor effect.
中文翻译:
Auriculasin 增强 ROS 生成以调节结直肠癌细胞凋亡、铁死亡、oxeiptosis、侵袭和集落形成
结直肠癌(CRC)是消化系统最常见的恶性肿瘤之一,中草药在肿瘤治疗中发挥着重要作用。对从Flemingia philippinensis中分离得到的 auriculasin 的深入研究表明,auriculasin 以浓度依赖性方式促进活性氧 (ROS) 的产生;添加 ROS 清除剂 NAC 后,木耳素促进 ROS 生成和抑制细胞活力的作用被阻断。Auriculasin诱导CRC细胞凋亡,导致线粒体收缩,并增加细胞内Fe 2+和MDA的积累。同时加入金针菇和NAC时,细胞凋亡、Fe 2+和MDA恢复到对照组水平,表明auriculasin通过诱导ROS产生激活细胞凋亡和铁死亡。此外,auriculasin 促进 Keap1 和 AIFM1 的表达,但显着降低了 AIFM1 的磷酸化水平,而 NAC 显着阻断了 auriculasin 对 Keap1 和 AIFM1 的调节,这表明 auriculasin 还可以通过 ROS 诱导 oxeiptosis。当分别加入Z-VAD-FMK、Ferrostatin-1、Keap1 siRNA、PGAM5 siRNA和AIFM1 siRNA时,木耳素对细胞活力的抑制作用明显减弱,说明木耳素通过诱导细胞凋亡、铁死亡和去细胞凋亡来抑制细胞活力。Auriculasin还抑制CRC细胞的侵袭和克隆形成能力,而NAC阻断了auriculasin的上述作用。所以,