Title page for etd-0720114-004147


[Back to Results | New Search]

URN etd-0720114-004147
Author Yu-Ting Peng
Author's Email Address No Public.
Statistics This thesis had been viewed 5568 times. Download 0 times.
Department Institute of Biomedical Sciences
Year 2013
Semester 2
Degree Master
Type of Document
Language English
Title Studies on the regulatory mechanisms of GTN-induced protein kinase inhibitors in hepatocellular carcinoma-derived cells
Date of Defense 2014-07-28
Page Count 67
Keyword
  • E3-ligase inhibitor
  • HDAC inhibitor
  • Goniothalamin (GTN)
  • CDKN1B
  • Cyclin-dependent kinase inhibitors (CKIs)
  • CDKN1C
  • Abstract 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.
    Advisory Committee
  • Yao-tsung Yeh - chair
  • Hung-Wen Huamg - co-chair
  • Yow-Ling Shiue - advisor
  • Files
  • etd-0720114-004147.pdf
  • Indicate in-campus at 99 year and off-campus access at 99 year.
    Date of Submission 2014-08-20

    [Back to Results | New Search]


    Browse | Search All Available ETDs

    If you have more questions or technical problems, please contact eThesys