Toxic and metabolic effect of sodium butyrate on SAS tongue cancer cells: role of cell cycle deregulation and redox changes.
Butyrate is a metabolite produced by oral and colonic microorganism. Butyrate has been shown to reduce colon cancer, whereas its role in oral carcinogenesis is not clear. Butyrate concentration in dental plaque and saliva ranged from 0.2 to 16 mM. In this study, we found that sodium butyrate inhibited the growth of SAS tongue cancer cells by 32% and 53% at concentrations of 1 and 2mM, respectively. Low concentrations of sodium butyrate (1-8mM) induced G0/G1 cell cycle arrest of SAS cells, whereas concentrations of 4-16 mM elicited G2/M arrest and a slight increase in apoptotic cell populations. These events were concomitant with induction of intracellular reactive oxygen species (ROS) production. An elevation in p21 mRNA and protein level was noted in SAS cells by sodium butyrate. On the contrary, a decline of cyclin Bl, cdc2 and cdc25C mRNA and protein expression in SAS cells was found after exposure to sodium butyrate. In addition, no evident increase in cdc2 inhibitory phosphorylation was found in sodium butyrate-treated SAS cancer cells. Inclusion of N-acetyl-l-cysteine (NAC) (3mM), catalase (1000 U/ml) and dimethylthiourea (DMT, 5mM), and also SOD (500 U/ml) attenuated the sodium butyrate-induced ROS production in SAS cells. However, they were not able to prevent the cell cycle arrest, apoptosis and growth inhibition in SAS cells induced by 1, 2 and 16 mM of sodium butyrate. These results indicate that sodium butyrate is toxic and inhibits the tongue cancer cell growth via induction of cell cycle arrest and apoptosis. Sodium butyrate mediates these events by mechanisms additional to ROS production.
Jeng
Jiiang-Huei
JH
Laboratory of Dental Pharmacology and Toxicology, Department of Dentistry, National Taiwan University Hospital and Medical College, National Taiwan University, Taipei, Taiwan.
Kuo
Mark Yen-Ping
MY
Lee
Po-Hsuen
PH
Wang
Ying-Jan
YJ
Lee
Mon-Ying
MY
Lee
Jang-Jaer
JJ
Lin
Bor-Ru
BR
Tai
Tseng-Fang
TF
Chang
Mei-Chi
MC
D017209:Apoptosis / Q000187:drug effects; D002087:Butyrates / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects*; D018797:Cell Cycle Proteins / Q000235:genetics; D045744:Cell Line, Tumor; D016166:Free Radical Scavengers / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014062:Tongue Neoplasms / Q000378:metabolism / Q000473:pathology
D002087:Butyrates; D018797:Cell Cycle Proteins; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species