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

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43 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1903-1911
Number of pages9
JournalJournal of Medicinal Chemistry
Issue number7
Publication statusPublished - 2009 Apr 9

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

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