2-methoxyestradiol enhances p53 protein transduction therapy-associated inhibition of the proliferation of oral cancer cells through the suppression of NFkappaB activity.
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.
Takata
Hidehiko
H
Department of Physiology, Okayama University Graduate School of Medicine and Dentistry, Okayama 700-8558, Japan.
Tomizawa
Kazuhito
K
Matsushita
Masayuki
M
Matsui
Hideki
H
D000077584:2-Methoxyestradiol; D002294:Carcinoma, Squamous Cell; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D004359:Drug Therapy, Combination; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006801:Humans; D009062:Mouth Neoplasms; D016328:NF-kappa B / Q000378:metabolism*; D010455:Peptides / Q000235:genetics / Q000493:pharmacokinetics; D011993:Recombinant Fusion Proteins / Q000493:pharmacokinetics; D014158:Transcription, Genetic / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000493:pharmacokinetics*
D016328:NF-kappa B; D010455:Peptides; D011993:Recombinant Fusion Proteins; D016159:Tumor Suppressor Protein p53; C015462:polyarginine; D004958:Estradiol; D000077584:2-Methoxyestradiol