https://scholars.lib.ntu.edu.tw/handle/123456789/523709
標題: | Phenanthrene-based tylophorine-1 (PBT-1) inhibits lung cancer cell growth through the Akt and NF-κB pathways | 作者: | Lin J.-C. Yang S.-C. Hong T.-M. SUNG-LIANG YU Qian S. Linyi W. Chen H.-Y. PAN-CHYR YANG Lee K.-H. |
公開日期: | 2009 | 卷: | 52 | 期: | 7 | 起(迄)頁: | 1903-1911 | 來源出版物: | Journal of Medicinal Chemistry | 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. ? 2009 American Chemical Society. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-64549149739&doi=10.1021%2fjm801344j&partnerID=40&md5=fb981ee3648b3fc543f291b6d6eb76bc https://scholars.lib.ntu.edu.tw/handle/123456789/523709 |
ISSN: | 0022-2623 | DOI: | 10.1021/jm801344j | SDG/關鍵字: | carisoprodol; cyclooxygenase 2; I kappa B kinase alpha; immunoglobulin enhancer binding protein; mitogen activated protein kinase; phenanthrene based tylophorine 1; phenanthrene based tylophorine 10; phenanthrene based tylophorine 2; phenanthrene based tylophorine 3; phenanthrene based tylophorine 4; phenanthrene based tylophorine 5; phenanthrene based tylophorine 6; phenanthrene based tylophorine 7; phenanthrene based tylophorine 8; phenanthrene based tylophorine 9; phenanthrene derivative; protein kinase B; transcription factor RelB; tylophorine; unclassified drug; antineoplastic activity; apoptosis; article; cancer inhibition; cell cycle arrest; cell cycle G2 phase; cell cycle M phase; clonogenesis; concentration response; controlled study; cytotoxicity; DNA microarray; drug effect; drug structure; focal adhesion; gene expression; genetic transcription; human; human cell; IC 50; lung cancer; nucleotide sequence; protein degradation; protein phosphorylation; Antineoplastic Agents; Apoptosis; Cell Division; Cell Line, Tumor; Cell Proliferation; Drug Screening Assays, Antitumor; Focal Adhesions; G2 Phase; Gene Expression Regulation; Humans; Lung Neoplasms; NF-kappa B; Phenanthrenes; Phosphorylation; Proto-Oncogene Proteins c-akt; Signal Transduction; Structure-Activity Relationship; Transcription, Genetic |
顯示於: | 醫學系 |
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