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

35 引文 (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

Lung Neoplasms
Growth
G2 Phase Cell Cycle Checkpoints
Apoptosis
phenanthrene
tylophorine
NFI Transcription Factors
Focal Adhesions
Microarray Analysis
Mitogen-Activated Protein Kinases
Oligonucleotide Array Sequence Analysis
Genetic Promoter Regions
Antineoplastic Agents
Phosphotransferases
Down-Regulation
Gene Expression
Drug Therapy
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

引用此文

Lin, Jau Chen ; Yang, Shuenn Chen ; Hong, Tse-Ming ; Yu, Sung Liang ; Qian, Shi ; Linyi, Wei ; Chen, Hsuan Yu ; Yang, Pan Chyr ; Lee, Kuo Hsiung. / Phenanthrene-based tylophorine-1 (PBT-1) inhibits lung cancer cell growth through the Akt and NF-κB pathways. 於: Journal of Medicinal Chemistry. 2009 ; 卷 52, 編號 7. 頁 1903-1911.
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Phenanthrene-based tylophorine-1 (PBT-1) inhibits lung cancer cell growth through the Akt and NF-κB pathways. / Lin, Jau Chen; Yang, Shuenn Chen; Hong, Tse-Ming; Yu, Sung Liang; Qian, Shi; Linyi, Wei; Chen, Hsuan Yu; Yang, Pan Chyr; Lee, Kuo Hsiung.

於: Journal of Medicinal Chemistry, 卷 52, 編號 7, 09.04.2009, p. 1903-1911.

研究成果: Article

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AU - Qian, Shi

AU - Linyi, Wei

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