Transcriptome Profiling and Cytological Assessments for Identifying Regulatory Pathways Associated With Diorcinol N-Induced Autophagy in A3 Cells.
Transcriptome Profiling and Cytological Assessments for Identifying Regulatory Pathways Associated With Diorcinol N-Induced Autophagy in A3 Cells.
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转录组分析和细胞学评估，用于识别 A3 细胞中与二癸醇 N 诱导的自噬相关的调控途径
DOI：
10.3389/fphar.2020.570450
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发表时间：
2020
影响因子：
5.6
通讯作者：
Zhang P
中科院分区：
文献类型：
--
作者：
Yuan XL;Li XQ;Xu K;Hou XD;Zhang ZF;Xue L;Liu XM;Zhang P
真菌次生代谢产物为探索具有药用价值的先导化合物提供了丰富的资源。Diorcinol N （DN）是一种从内生真菌Arthrinium arundinis中分离出来的真菌次级代谢物，具有很强的抗癌活性。然而，DN的抗癌机制尚不清楚。在本研究中，我们检测了DN对不同人类癌细胞系的生长抑制作用。我们发现DN以时间和浓度依赖性的方式降低A3 t细胞白血病细胞的活力。转录组分析表明，DN调节了A3细胞的转录组。共发现9340个差异表达基因，其中下调基因4378个，上调基因4962个，主要参与自噬、细胞周期和DNA复制。此外，我们证明了DN诱导A3细胞自噬，细胞周期阻滞在G1/S期，下调自噬和细胞周期相关基因的表达。我们用吖啶橙/溴化乙啶、Hoechst 33,258和单氨尸胺标记A3细胞，并通过透射电镜发现，DN增加了质膜通透性、结构破坏、空泡化和自噬体的形成。我们的研究为DN在t细胞白血病（A3）细胞中的抗癌活性机制提供了证据，并证明了DN作为治疗急性淋巴细胞白血病的先导甚至候选分子的前景。
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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影响因子：
7.7
作者：
Karch J;Schips TG;Maliken BD;Brody MJ;Sargent MA;Kanisicak O;Molkentin JD
通讯作者：
Molkentin JD
影响因子：
3.3
作者：
Kang, YK;Kim, WH;Jang, JJ
通讯作者：
Jang, JJ
影响因子：
3.3
作者：
Braun, Katherine A.;Breeden, Linda L.
通讯作者：
Breeden, Linda L.
影响因子：
2.3
作者：
Kazemi, Alireza;Sadri, Mohammadreza;Atashi, Amir
通讯作者：
Atashi, Amir
影响因子：
13.3
作者：
Laha, Dipranjan;Deb, Moonmoon;Das, Hiranmoy
通讯作者：
Das, Hiranmoy