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Phenanthrene-Based Tylophorine-1 (PBT-1) Inhibits Lung Cancer Cell Growth through the Akt and NF-κB Pathways.
- Source :
-
Journal of Medicinal Chemistry . Apr2009, Vol. 52 Issue 7, p1903-1911. 9p. - Publication Year :
- 2009
-
Abstract
- 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-α 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00222623
- Volume :
- 52
- Issue :
- 7
- Database :
- Academic Search Index
- Journal :
- Journal of Medicinal Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 37343078
- Full Text :
- https://doi.org/10.1021/jm801344j