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Heptaphylline inhibits the proliferation and epithelial to mesenchymal transition of human pancreatic cancer cells via induction of apoptosis and autophagy
Frontiers in Life Science Pub Date : 2021-05-20 , DOI: 10.1080/26895293.2021.1925357
Zhongyan Zhang 1 , Hongyan Zhang 2 , Huanlian Yang 3 , Zhenglei Xu 4
Affiliation  

Heptaphylline, a carbazole alkaloid, has been shown to exert anticancer effects against different human cancers. The study was designed to evaluate the anticancer effects of heptaphylline against the human pancreatic cancer cell and to explore the underlying mechanism. The results showed that heptaphylline inhibited the proliferation of all the pancreatic cancer cell lines with lowest IC50 of 12 µM against the PANC1 cells. In contrary, the IC50 of heptaphylline was around eight times higher against the normal H6c7 cells. The transwell assays revealed heptaphylline inhibited the migration and invasion of pancreatic cancer cells in a concentration-dependent manner. Additionally, the epithelial to mesenchymal transition of the PANC1 cells was also inhibited upon treatment with heptaphylline. The antiproliferative effects of heptaphylline were exerted via induction of apoptosis in pancreatic cancer cells. The apoptosis was associated with an increase in Bax, decrease in Bcl-2 expression, discharge of cytochrome c and cleavage of PARP, caspase-3 and caspase-9. AO staining revealed that heptaphylline induced autophagy in PANC1 cancer cells by increasing the expression of LC3B-II and Beclin-1. Taken together, heptaphylline suppresses the growth of pancreatic cancer via induction of apoptosis and autophagy and may prove a potent lead molecule for the development of chemotherapy.



中文翻译:

Heptaphylline通过诱导凋亡和自噬作用抑制人胰腺癌细胞的增殖和上皮向间充质转化。

已经证明庚烷,一种咔唑生物碱,对不同的人类癌症具有抗癌作用。该研究旨在评估七茶碱对人胰腺癌细胞的抗癌作用,并探讨其潜在机制。结果表明,七氢茶碱抑制所有胰腺癌细胞系对PANC1细胞的增殖,最低IC 50为12 µM。相反,IC 50与正常的H6c7细胞相比,七氢茶碱的含量大约高出八倍。Transwell分析显示七氢茶碱以浓度依赖的方式抑制胰腺癌细胞的迁移和侵袭。另外,在用七茶碱处理后,PANC1细胞的上皮向间质转化也受到抑制。茶碱的抗增殖作用是通过诱导胰腺癌细胞凋亡来发挥的。细胞凋亡与Bax的增加,Bcl-2表达的减少,细胞色素c的释放以及PARP,caspase-3和caspase-9的裂解有关。AO染色显示,茶碱通过增加LC3B-II和Beclin-1的表达诱导PANC1癌细胞自噬。在一起

更新日期:2021-05-20
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