雷公藤醇
细胞周期
细胞凋亡
癌症研究
细胞生长
细胞周期检查点
G1期
化学
细胞
信号转导
细胞生物学
生物
生物化学
作者
Jiabin Zhu,Hua Zhang,Xiaojin Zhao,Shang Fajun,Huan Sun,Xu Zheng
出处
期刊:Anti-cancer Agents in Medicinal Chemistry
[Bentham Science]
日期:2022-05-12
卷期号:22 (10): 1921-1932
被引量:5
标识
DOI:10.2174/1871520621666211103103530
摘要
Colorectal cancer (CRC) is the third-ranked malignant tumor in the world that contributes to the death of a major population of the world. Celastrol, a bioactive natural product isolated from the medicinal plant Tripterygium wilfordii Hook F, has been proved to be an effective anti-tumor inhibitor for multiple tumors.To reveal the therapeutic effect and underlying mechanisms of celastrol on CRC cells.CCK-8 and clonogenic assay were used to analyze the cell proliferation in CRC cells. Flow cytometry analysis was conducted to assess the cell cycle and cell apoptosis. Wound-healing and cell invasion assay were used to evaluate the migrating and invasion capability of CRC cells. The potential antitumor mechanism of celastrol was investigated by qPCR, western blot, and confocal immunofluorescence analyses.Celastrol effectively inhibited CRC cell proliferation by activating caspase-dependent cell apoptosis and facilitating G1 cell cycle arrest in a dose-dependent manner, as well as cell migration and invasion by downregulating the MMP2 and MMP9. Mechanistic protein expression revealed that celastrol suppressed the expression of COX-2 by inhibiting the phosphorylation of NF-κB p65 and subsequently leading to cytoplasmic retention of p65 protein, thereby inhibiting its nuclear translocation and transcription activities.These findings indicate that celastrol is an effective inhibitor for CRC, regulating the NF-κB/COX-2 pathway, leading to the inhibition of cell proliferation characterized by cell cycle arrest and caspase-dependent apoptosis, providing a potential alternative therapeutic agent for CRC patients.
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