1. Phenanthrene-Based Tylophorine-1 (PBT-1) Inhibits Lung Cancer Cell Growth through the Akt and NF-κB Pathways.
- Author
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Jau-Chen Lin, Shuenn-Chen Yang, Tse-Ming Hong, Sung-Liang Yu, Qian Shi, Linyi Wei, Hsuan-Yu Chen, Pan-Chyr Yang, and Kuo-Hsiung Lee
- Subjects
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CANCER cell growth regulation , *PHENANTHRENE , *NATURAL products , *ANTINEOPLASTIC agents , *APOPTOSIS , *DRUG dosage , *DOSE-response relationship in biochemistry ,THERAPEUTIC use of alkaloids - 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]
- Published
- 2009
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