Akt-targeting compounds inhibit cellular proliferation and induce apoptosis in zebrafish hosting lung cancer xenografts
| Autor: | Mei-Chien Lu, 盧美潔 |
|---|---|
| Rok vydání: | 2014 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 102 Lung cancer is the leading cause of cancer death in males and females worldwide. The non-small cell lung cancer (NSCLC) accounts for at least 85% lung cancer and easily metastasizes to other organs such as brain, liver and bone. Akt, a serine/threonine-specific protein kinase, which is known to regulate various cellular physiologies, including cellular survival, proliferation, migration and angiogenesis. Constitutive phosphorylation or over-expression of Akt was frequently observed in NSCLC cells. Recently studies showed that Akt targeting may be a promising approach for lung cancer treatment. Besides, quinone compounds are formally derived from aromatic compounds such as benzene or naphthalene. Quinone derivative was reported to exert the antitumor activity. Accordingly, we used bioinformatics approaches to screen twelve quinone-based compounds which exhibit Akt-targeting potential. In the preliminary results, we found that one of the Akt-targeting compounds quinone X1, exerts a moderate cytotoxicity towards NSCLC tumor H1299 cells. Concomitantly, the Akt-targeting compound quinone X1 causes the polyploidy and DNA double strand breaks associates ROS in H1299 cells. A significant apoptotic population was observed in quinone X1-treated H1299 cells. Additionally, quinone X1 inhibits both the invasion and colony formation of H1299 cells. Consistently, the zebrafish xenograft assay also validates the anti-lung tumor effects of quinone X1. Accordingly to these above observations, our present work suggests that the application of Akt-targeting compound may be a promising approach for lung cancer treatment. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
| Externí odkaz: |
|