细胞凋亡
p38丝裂原活化蛋白激酶
MAPK/ERK通路
细胞周期
细胞生物学
活性氧
化学
膜联蛋白
细胞周期检查点
激酶
信号转导
癌细胞
癌症研究
生物
癌症
生物化学
遗传学
作者
Seung‐On Lee,Sang Hoon Joo,Ah‐Won Kwak,Mee‐Hyun Lee,Ji‐Hye Seo,Seung‐Sik Cho,Goo Yoon,Jung‐Il Chae,Jung‐Hyun Shim
出处
期刊:Biomolecules & Therapeutics
[The Korean Society of Applied Pharmacology]
日期:2021-10-13
卷期号:29 (6): 658-666
被引量:14
标识
DOI:10.4062/biomolther.2021.143
摘要
Podophyllotoxin (PT), a lignan compound from the roots and rhizomes of Podophyllum peltatum, has diverse pharmacological activities including anticancer effect in several types of cancer. The molecular mechanism of the anticancer effects of PT on colorectal cancer cells has not been reported yet. In this study, we sought to evaluate the anticancer effect of PT on human colorectal cancer HCT116 cells and identify the detailed molecular mechanism. PT inhibited the growth of cells and colony formation in a concentration-dependent manner and induced apoptosis as determined by the annexin V/7-aminoactinomycin D double staining assay. PT-induced apoptosis was accompanied by cell cycle arrest in the G2/M phase and an increase in the generation of reactive oxygen species (ROS). The effects of PT on the induction of ROS and apoptosis were prevented by pretreatment with N-acetyl-L-cysteine (NAC), indicating that an increase in ROS generation mediates the apoptosis of HCT116 cells induced by PT. Furthermore, Western blot analysis showed that PT upregulated the level of phospho (p)-p38 mitogen-activated protein kinase (MAPK). The treatment of SB203580, a p38 inhibitor, strongly prevented the apoptosis induced by PT, suggesting that PT-induced apoptosis involved the p38 MAPK signaling pathway. In addition, PT induced the loss of mitochondrial membrane potential and multi-caspase activation. The results suggested that PT induced cell cycle arrest in the G2/M phase and apoptosis through the p38 MAPK signaling pathway by upregulating ROS in HCT116 cells.
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