Studies on the regulatory mechanisms of GTN-induced protein kinase inhibitors in hepatocellular carcinoma-derived cells
| Autor: | Yu-Ting Peng, 彭鈺婷 |
|---|---|
| Rok vydání: | 2014 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 102 The study was to investigate the regulatory mechanisms of goniothalamin (GTN)-induced protein kinase inhibitors, which means cyclin-dependent kinase inhibitors (CKIs), in two hepatocellular carcinoma (HCC)-derived cell lines, Huh-7 and Hep-3B. GTN is a styrylpyrone derivative, is a natural compound with potent cytotoxic and antiporliferative effects for several types of cancer cells. Nonetheless, the detail regulatory mechanisms of GTN in HCC-derived cells have not been investigated before. Results indicated that GTN induced CDKN1B/p27Kip1 protein expression through inhibiting SKP2 protein expression in Huh-7 cells; triggered CDKN1C/p57Kip2 mRNA expression by epigenetic modification in Hep-3B cells. After GTN treatment, SKP2, the specific E3-ligase for CDKN1B in nuclear, was significantly decreasing in protein level but not in mRNA level. This result lead cancer cells to slow down the proliferation and contribute to apoptosis in the Huh-7 cells. Thus, GTN might have the activity of E3-ligase inhibitor in Huh-7 cells. On the other hand, CDKN1C is a tumor suppressor gene in mammalian cells and it might be regulated by epigenetic modification. In Hep-3B cells, the mRNA expression of CDKN1C was induced by GTN, and synergistic increased by trichostatin A (TSA) treatment. We also found the GTN might induce acetylation of histone 3 expression. It suggested the mechanism of GTN might similar to TSA and had a potential inhibition to histone deacetylase (HDAC) in Hep-3B cells. In summary, GTN might represent a novel of anticancer drug that induces CKIs expression in HCC-derived cell lines through plays E3-ligase inhibitor and HDAC inhibitor. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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