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ID 32086
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Author
Takata, Hidehiko
Tomizawa, Kazuhito
Matsushita, Masayuki
Abstract

Protein transduction therapy using poly-arginine peptide can deliver the biologically active proteins. A previous study showed that 11 poly-arginine fused p53 protein (11R-p53) effectively penetrated across the plasma membrane and inhibited the proliferation of oral cancer cells. However, the intracellular half-life of the delivered protein was less than 36 h. Previous studies also showed that 2-methoxyestradiol (2-ME), an endogenous non-toxic estrogenic metabolite, induces the stabilization of the wild-type p53 protein in human cancer cells posttranscriptionally. In the present study, we examined whether 2-ME induced the stabilization of 11R-p53 and had an inhibitory effect on the proliferation of oral cancer cells. The application of 2-ME significantly enhanced the inhibitory effect of 11R-p53 on the proliferation of oral cancer cells. However, 2-ME had no effect on the intracellular half-life of 11R-p53 in oral cancer cells. Of interest is the finding that 2-ME suppressed the transcriptional activity of NFkappaB, which has an important role in tumorigenesis, but did not affect p53 transcriptional activity. These results suggest that 2-ME synergistically enhances the 11R-p53-induced inhibition of the proliferation of oral cancer cells through the suppression of NFkB transcription.

Keywords
tumor
TAT
poly arginine
gene therapy
protein therapy
Amo Type
Article
Published Date
2004-08
Publication Title
Acta Medica Okayama
Volume
volume58
Issue
issue4
Publisher
Okayama University Medical School
Start Page
181
End Page
187
ISSN
0386-300X
NCID
AA00508441
Content Type
Journal Article
language
英語
File Version
publisher
Refereed
True
PubMed ID
Web of Science KeyUT