Induction of apoptosis in human gastric cancer by sodium butyrate.
BACKGROUND
Novel therapeutic agents are needed in the adjuvant treatment of gastric cancer. The differentiating agent sodium butyrate (NaBT) inhibits the growth of colon cancer cells; its effects on gastric cancers are not known. The purpose of our study was to characterize the effects of NaBT on human gastric cancer.


METHODS
The human gastric cancer, SIIA, was treated with NaBT (5 mM) for 12-72 h. Cell number, viability and death were measured. Expression levels of the tumor-suppressor protein, p53, the cell-cycle inhibitors, p21Waf1/Cip1 and p27Kip1, and the pro-apoptotic proteins, Bax, Bak, and Bik, were determined.


RESULTS
NaBT significantly inhibited SIIA gastric cancer cell proliferation in a time-dependent fashion by a process involving the induction of apoptosis. Treatment with NaBT was associated with increased expression levels of p21Waf1/Cip1 p27Kip1, Bax, Bak, and Bik.


CONCLUSIONS
NaBT triggers growth arrest and apoptosis in the human gastric cancer SIIA potentially through the induction of the cell-cycle inhibitors, p21Waf1/Cip1 and p27Kip1, and the proapoptotic genes, Bax, Bak, and Bik. NaBT may be an effective adjuvant agent in the treatment of gastric cancer.
Litvak
D A
DA
Department of Surgery, University of Texas Medical Branch, Galveston 77555, USA.
Hwang
K O
KO
Evers
B M
BM
Townsend
C M
CM
D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins; D002087:Butyrates / Q000633:toxicity*; D018797:Cell Cycle Proteins; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016213:Cyclins / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D019254:Genes, bcl-2; D016158:Genes, p53; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D008869:Microtubule-Associated Proteins / Q000235:genetics; D024101:Mitochondrial Proteins; D011506:Proteins / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D013274:Stomach Neoplasms; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein
D051017:Apoptosis Regulatory Proteins; C494772:BAK1 protein, human; C494826:BAX protein, human; C096820:BIK protein, human; D002087:Butyrates; C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D025521:Tumor Suppressor Proteins; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D050760:Cyclin-Dependent Kinase Inhibitor p27