中国病理生理杂志2024,Vol.40Issue(4):594-601,8.DOI:10.3969/j.issn.1000-4718.2024.04.003
N-甲基芸香碱通过调控ERK通路诱导人胶质母细胞瘤细胞凋亡和自噬
Induction of apoptosis and autophagy in human glioblastoma cells by N-methylflindersine:insights into regulatory role of ERK pathway
摘要
Abstract
AIM:Mangrove-associated plants are known for producing natural compounds with antitumor ac-tivity.Despite the potential therapeutic value of these compunds,the molecular mechanisms underlying their antitumor ef-fects remain unclear.This study aimed to investigate the antitumor properties of N-methylflindersine,an alkaloid derived from the mangrove-associated plant,Micromelum falcatum(Lour.)Tan.,and its effects on U87 human glioblastoma cells.METHODS:We identified and isolated 15 compounds from the stem bark of Micromelum falcatum.Among these,we screened N-methylflindersine for its potential inhibitory effects on U87 cell growth.Various assays,including wound healing,Hoechst 33342/PI staining,and protein expression analysis,were conducted to investigate the compound's im-pact on cell migration,apoptosis,and autophagy-related proteins.RESULTS:Within 24 h,N-methylflindersine demon-strated the ability to reduce U87 cell migration and increase the apoptotic U87 cell population.Furthermore,it downregu-lated the anti-apoptosis protein Bcl-2 expression,upregulated the pro-apoptosis protein Bax expression,and elevated the ratio of autophagy-related protein LC3-Ⅱ/LC3-Ⅰ in U87 cells.Additionally,the ERK signaling pathway was found to be down-regulated following N-methylflindersine treatment.CONCLUSION:N-methylflindersine appears to induce both apoptosis and autophagic cell death in U87 cells,resulting in reduced cell growth.This effect seems to be associated with the downregulation of the ERK signaling pathway.关键词
红树林相关植物/N-甲基芸香碱/胶质母细胞瘤Key words
mangrove-associated plants/N-methylflindersine/glioblastoma分类
医药卫生引用本文复制引用
黎思源,刘靖,王宗明,王欣,罗宇悠,罗雄明,王仲宇,陈晖彤,樊东,袁星怡,陈乐,唐佩..N-甲基芸香碱通过调控ERK通路诱导人胶质母细胞瘤细胞凋亡和自噬[J].中国病理生理杂志,2024,40(4):594-601,8.基金项目
Supported by the National Natural Science Foundation of China for Young Scholars(No.81802678),the Guangdong Natural Science Foundation Project(No.2018A030310107),the Guangzhou Basic and Applied Basic Research Founda-tion(No.202102021116 (No.81802678)
No.202201010307 ()
No.202201010299),and the Guangdong Province Administration of Traditional Chi-nese Medicine Project(No.20231210). (No.20231210)