| RRC ID |
44392
|
| Author |
Fukuda Y, Kanbe M, Watanabe M, Dan K, Matsuzaki K, Kitanaka S, Miyata S.
|
| Title |
3EZ,20Ac-ingenol, a catalytic inhibitor of topoisomerases, downregulates p-Akt and induces DSBs and apoptosis of DT40 cells.
|
| Journal |
Arch Pharm Res
|
| Abstract |
We have previously reported that many ingenol compounds derived from Euphorbia kansui exhibit topoisomerase (topo) II inhibitory activity. Of these compounds, 3EZ,20Ac-ingenol inhibited topo I activity. Camptothecin, which inhibits the religation activity of topo I without interfering with the binding of topo I to DNA and induces topo I-mediated DNA cleavage, was used as a positive control. In this study, we found that 3EZ,20Ac-ingenol did not hamper the binding of topo I to DNA in the same manner as camptothecin but affected the inhibition of cleavage of one DNA strand. 3EZ,20Ac-ingenol inhibited cell proliferation by blocking cell cycle progression in the G2/M phase. To define the mechanism of inhibition of DT40 cell proliferation, the change in Akt activity was observed because Akt activity is regulated in response to DNA damage. Western blot analysis revealed that 3EZ,20Ac-ingenol downregulated the expression of p-Akt, and apoptosis was detected by the presence of DNA double-strand breaks and caspase 3 activation.
|
| Volume |
36(8)
|
| Pages |
1029-38
|
| Published |
2013-8-1
|
| DOI |
10.1007/s12272-013-0108-4
|
| PMID |
23595550
|
| PMC |
PMC3731510
|
| MeSH |
Animals
Apoptosis / drug effects*
Apoptosis / physiology
Catalysis
Cell Proliferation / drug effects
Chickens
DNA Breaks, Double-Stranded / drug effects*
Diterpenes / chemistry
Diterpenes / pharmacology*
Dose-Response Relationship, Drug
Down-Regulation / drug effects*
Down-Regulation / physiology
Proto-Oncogene Proteins c-akt / antagonists & inhibitors*
Proto-Oncogene Proteins c-akt / metabolism
Topoisomerase Inhibitors / chemistry
Topoisomerase Inhibitors / pharmacology*
|
| IF |
2.934
|
| Times Cited |
7
|
|
WOS Category
|
PHARMACOLOGY & PHARMACY
CHEMISTRY, MEDICINAL
|
| Resource |
| Human and Animal Cells |
DT40(RCB1464)
ΔBLM-DT40(RCB1811)
ΔWRN-DT40(RCB1812) |
