NF-kappaB signaling pathway is involved in growth inhibition, G2/M arrest and apoptosis induced by Trichostatin A in human tongue carcinoma cells.
The HDAC inhibitor Trichostatin A (TSA) exhibits antitumour activity in various tumour cells. However, little is known about the effect of TSA on growth of human tongue carcinoma cells. In this study, we observed that TSA concentration-dependently inhibited growth of human tongue carcinoma Tca8113 cells by inducing G2/M arrest, apoptosis, up-regulation of the pro-apoptotic protein Bax and down-regulation of the anti-apoptotic proteins Bcl-2 and Bcl-XL which are regulated by the transcription factor nuclear factor (NF)-kappaB. Coincident with this observation, TSA induced a concentration-dependent reduction of constitutive and tumour necrosis factor (TNF)-alpha-induced NF-kappaB activation in Tca8113 cells. This induction was correlated with decreased phosphorylation and increased expression of inhibitors of NF-kappaB (IkappaB)alpha induced by TSA. Overall, our results indicate inhibition of NF-kappaB activation contributes, at least partially, to the antitumour activity of TSA in human tongue carcinoma cells.
Yao
Jun
J
School of Medicine, Wuhan University, Wuhan, Hubei 430071, PR China.
Duan
Li
L
Fan
Mingwen
M
Wu
Xinxing
X
D017209:Apoptosis / Q000187:drug effects*; D001562:Benzimidazoles; D015153:Blotting, Western; D002277:Carcinoma / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D024202:Electrophoretic Mobility Shift Assay; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D016195:G2 Phase / Q000187:drug effects; D019254:Genes, bcl-2 / Q000187:drug effects; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D016328:NF-kappa B / Q000502:physiology*; D010766:Phosphorylation; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D015398:Signal Transduction / Q000502:physiology*; D014062:Tongue Neoplasms / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis / Q000235:genetics; D051020:bcl-X Protein / Q000096:biosynthesis / Q000235:genetics
D001562:Benzimidazoles; D005456:Fluorescent Dyes; D006877:Hydroxamic Acids; D016328:NF-kappa B; D011500:Protein Synthesis Inhibitors; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; C012589:trichostatin A; C017807:bisbenzimide ethoxide trihydrochloride