Phenanthrene-based tylophorine-1 (PBT-1) inhibits lung cancer cell growth through the Akt and NF-κB pathways

Jau Chen Lin, Shuenn Chen Yang, Tse Ming Hong, Sung Liang Yu, Shi Qian, Wei Linyi, Hsuan Yu Chen, Pan Chyr Yang, Kuo Hsiung Lee

研究成果: Article

36 引文 斯高帕斯(Scopus)

摘要

Tylophorine and related natural compounds exhibit potent antitumor activities. We previously showed that PBT-1, a synthetic C9-substituted phenanthrene-based tylophorine (PBT) derivative, significantly inhibits growth of various cancer cells. In this study, we further explored the mechanisms and potential of PBT-1 as an anticancer agent. PBT-1 dose-dependently suppressed colony formation and induced cell cycle G2/M arrest and apoptosis. DNA microarray and pathway analysis showed that PBT-1 activated the apoptosis pathway and mitogen-activated protein kinase signaling. In contrast, PBT-1 suppressed the nuclear factor kappaB (NF-κB) pathway and focal adhesion. We further confirmed that PBT-1 suppressed Akt activation accelerated RelA degradation via IκB kinase-R and down-regulated NF-κB target gene expression. The reciprocal recruitment of RelA and RelB on COX-2 promoter region led to down-regulation of transcriptional activity. We conclude that PBT-1 induces cell cycle G2/M arrest and apoptosis by inactivating Akt and by inhibiting the NF-κB signaling pathway. PBT-1 may be a good drug candidate for anticancer chemotherapy.

原文English
頁(從 - 到)1903-1911
頁數9
期刊Journal of Medicinal Chemistry
52
發行號7
DOIs
出版狀態Published - 2009 四月 9

    指紋

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

引用此

Lin, J. C., Yang, S. C., Hong, T. M., Yu, S. L., Qian, S., Linyi, W., Chen, H. Y., Yang, P. C., & Lee, K. H. (2009). Phenanthrene-based tylophorine-1 (PBT-1) inhibits lung cancer cell growth through the Akt and NF-κB pathways. Journal of Medicinal Chemistry, 52(7), 1903-1911. https://doi.org/10.1021/jm801344j