Bcl-2 related proteins are dramatically induced at the early stage of differentiation in human liver cancer cells by a histone deacetylase inhibitor projecting an anti-apoptotic role during this period.
Expression of the Bcl-2 family members in a human hepatocellular carcinoma cell line (HCC-T) after sodium butyrate-treatment was investigated. Sodium butyrate, a histone deacetylase inhibitor, induced differentiation of the cell line into its normal counterpart without inducing apoptosis at the concentration of 2 mmol/l. Since sodium butyrate has effects on both differentiation and apoptosis, we investigated the expression profile of bcl-2 related genes in HCC-T. The expression of Bcl-2 and Mcl-1/EAT was up-regulated 4-12 h after the treatment while Bcl-XL was up-regulated 2-3 days after the stimulation. On the other hand, the expression levels of Bax protein remained unchanged during differentiation. The HCC-T cells entered a cell cycle arrest at G1 and showed neither cellular fragmentation nor apoptosis during this period, which was concomitantly associated with up-regulated expression of a cell cycle regulator, p21WAF-1. These results demonstrate that induction of anti-apoptotic bcl-2 related proteins at an early stage of differentiation is important for the maintenance of HCC-T cell differentiation by antagonizing pro-apoptotic molecules such as Bax.
Wakabayashi
K
K
Department of Internal Medicine, School of Medicine, Keio University, Tokyo 160-8582, Japan.
Saito
H
H
Ebinuma
H
H
Saito
Y
Y
Takagi
T
T
Nakamura
M
M
Umezawa
A
A
Hata
J
J
Ishii
H
H
D017209:Apoptosis / Q000187:drug effects; D002087:Butyrates / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D002087:Butyrates; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D006655:Histone Deacetylases