2-Methoxyestradiol enhances p53 protein transduction therapy-associated inhibition of the proliferation of oral cancer cells through the suppression of NFκB activity

Hidehiko Takata, Kazuhito Tomizawa, Masayuki Matsushita, Hideki Matsui

Research output: Contribution to journalArticle

11 Citations (Scopus)

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 NFArB, 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 NFκB transcription.

Original languageEnglish
Pages (from-to)181-187
Number of pages7
JournalActa Medica Okayama
Volume58
Issue number4
Publication statusPublished - Aug 2004

Fingerprint

Mouth Neoplasms
Cells
Proteins
Half-Life
Arginine
Therapeutics
Stabilization
Transcription
Cell membranes
Metabolites
2-methoxyestradiol
Carcinogenesis
Cell Membrane
Peptides
Neoplasms

Keywords

  • Gene therapy
  • Poly arginine
  • Protein therapy
  • TAT
  • Tumor

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

2-Methoxyestradiol enhances p53 protein transduction therapy-associated inhibition of the proliferation of oral cancer cells through the suppression of NFκB activity. / Takata, Hidehiko; Tomizawa, Kazuhito; Matsushita, Masayuki; Matsui, Hideki.

In: Acta Medica Okayama, Vol. 58, No. 4, 08.2004, p. 181-187.

Research output: Contribution to journalArticle

Takata, Hidehiko ; Tomizawa, Kazuhito ; Matsushita, Masayuki ; Matsui, Hideki. / 2-Methoxyestradiol enhances p53 protein transduction therapy-associated inhibition of the proliferation of oral cancer cells through the suppression of NFκB activity. In: Acta Medica Okayama. 2004 ; Vol. 58, No. 4. pp. 181-187.
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