Transcriptome Profiling and Cytological Assessments for Identifying Regulatory Pathways Associated With Diorcinol N-Induced Autophagy in A3 Cells
文献类型: 外文期刊
第一作者: Yuan, Xiao-Long
作者: Yuan, Xiao-Long;Li, Xiu-Qi;Xu, Kuo;Hou, Xiao-Dong;Zhang, Zhong-Feng;Liu, Xin-Min;Zhang, Peng;Li, Xiu-Qi;Xue, Lin
作者机构:
关键词: acute lymphocytic leukemia; autophagy; diorcinol N; G1; S phase arrest; transcriptome profiling
期刊名称:FRONTIERS IN PHARMACOLOGY ( 影响因子:5.81; 五年影响因子:6.005 )
ISSN: 1663-9812
年卷期: 2020 年 11 卷
页码:
收录情况: SCI
摘要: Fungal secondary metabolites serve as a rich resource for exploring lead compounds with medicinal importance. Diorcinol N (DN), a fungal secondary metabolite isolated from an endophytic fungus, Arthrinium arundinis, exhibits robust anticancer activity. However, the anticancer mechanism of DN remains unclear. In this study, we examined the growth-inhibitory effect of DN on different human cancer cell lines. We found that DN decreased the viability of A3 T-cell leukemia cells in a time- and concentration-dependent manner. Transcriptome analysis indicated that DN modulated the transcriptome of A3 cells. In total, 9,340 differentially expressed genes were found, among which 4,378 downregulated genes and 4,962 upregulated genes were mainly involved in autophagy, cell cycle, and DNA replication. Furthermore, we demonstrated that DN induced autophagy, cell cycle arrest in the G1/S phase, and downregulated the expression of autophagy- and cell cycle-related genes in A3 cells. By labeling A3 cells with acridine orange/ethidium bromide, Hoechst 33,258, and monodansylcadaverine and via transmission electron microscopy, we found that DN increased plasma membrane permeability, structural disorganization, vacuolation, and autophagosome formation. Our study provides evidence for the mechanism of anticancer activity of DN in T-cell leukemia (A3) cells and demonstrates the promise of DN as a lead or even candidate molecule for the treatment of acute lymphoblastic leukemia.
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