Alantolactone induces apoptosis in THP‐1 cells through STAT3, survivin inhibition, and intrinsic apoptosis pathway,Chemical Biology & Drug Design

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Alantolactone induces apoptosis in THP‐1 cells through STAT3, survivin inhibition, and intrinsic apoptosis pathway
Chemical Biology & Drug Design ( IF 3.2 ) Pub Date : 2020-08-11 , DOI: 10.1111/cbdd.13778
Bashir Ahmad ₁ , Yaser Gamallat _{1,

2} , Pengyu Su ₁ , Akbar Husain ₁ , Ata Ur Rehman ₁ , Mohamed Y Zaky ₁ , Ahmed Musa Hago Bakheet ₃ , Naeem Tahir ₁ , Yi Xin ₁ , Wang Liang ₄

Affiliation

Cancer is the second foremost cause of mortality in the world, and THP‐1 cells play an important role in cancer progression. Alantolactone (ALT), a sesquiterpene lactone compound derived from Inula helenium, has a number of biological activities including antibacterial, antifungal, and anticancer. The current study was conducted to investigate the effects of ALT on THP‐1 cells and its underlying molecular mechanisms. THP‐1 cells were cultured and treated with ALT (20, 40 µM) for 12 hr, and 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide, cell morphology, live/dead, and apoptosis assays were performed. The gene expressions at the protein level were checked through Western blot. Results show that ALT decreased cell viability and increased cell death and apoptosis. We found that ALT inhibited STAT3 and survivin expression. Furthermore, ALT induced mitochondrial‐dependent apoptosis through a decrease in B‐cell lymphoma‐2 (Bcl‐2) and Bcl‐xL and increase in Bax expression, resulting in the release of cytochrome c (Cyt‐c) from mitochondria. Cyt‐c release from mitochondria further increased cleaved (cl) caspase‐3 and cl‐PARP expression and led the cells to apoptosis. Therefore, ALT might be a good therapy for the progression due to THP‐1 cells.

中文翻译：

阿兰内酯通过 STAT3、存活蛋白抑制和内在凋亡途径诱导 THP-1 细胞凋亡

癌症是世界上第二大死亡原因，而 THP-1 细胞在癌症进展中起着重要作用。Alantolactone (ALT)，一种源自Inula helenium的倍半萜内酯化合物，具有多种生物活性，包括抗菌、抗真菌和抗癌。目前的研究旨在研究 ALT 对 THP-1 细胞的影响及其潜在的分子机制。培养 THP-1 细胞并用 ALT (20, 40 µM) 和 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四唑处理 12 小时，细胞形态、活/死和进行了细胞凋亡测定。通过蛋白质印迹检查蛋白质水平的基因表达。结果显示ALT降低细胞活力并增加细胞死亡和细胞凋亡。我们发现ALT抑制STAT3和存活蛋白的表达。此外，ALT 通过减少 B 细胞淋巴瘤-2 (Bcl-2) 和 Bcl-xL 以及增加 Bax 表达来诱导线粒体依赖性细胞凋亡，导致线粒体释放细胞色素 c (Cyt-c)。从线粒体中释放的 Cyt-c 进一步增加了 cleaved (cl) caspase-3 和 cl-PARP 的表达，并导致细胞凋亡。因此，ALT 可能是治疗由 THP-1 细胞引起的进展的良好疗法。

更新日期：2020-08-11

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