Histone deacetylase inhibitor trichostatin A induces cell-cycle arrest/apoptosis and hepatocyte differentiation in human hepatoma cells.
Remodeling of the chromatin template by inhibition of HDAC activities represents a potential transcriptional therapy for neoplastic disease. A number of HDAC inhibitors that modulate in vitro cell growth and differentiation have been developed. We analyzed the effects of TSA, a specific and potent HDAC inhibitor, on the human hepatoma cell lines HepG2 and Huh-7. TSA increased levels of acetylated histones H3 and H4 in both HepG2 and Huh-7. It inhibited cell proliferation in vitro and induced G(0)/G(1) arrest in HepG2 and apoptosis in Huh-7. Gene expression of liver-specific functions and liver-enriched transcription factors was upregulated by TSA. TSA upregulated the ammonia removal rate and the albumin synthesis rate of HepG2 and Huh-7. Our results indicate that TSA can induce cell-cycle arrest/apoptosis and hepatocyte differentiation in human liver cancer cell lines.
Yamashita
Yo-ichi
Y
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. yamashi@surg2.med.kyushu-u.ac.jp
Shimada
Mitsuo
M
Harimoto
Norifumi
N
Rikimaru
Tatsuya
T
Shirabe
Ken
K
Tanaka
Shinj
S
Sugimachi
Keizo
K
D000418:Albumins / Q000378:metabolism; D000641:Ammonia / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors; D006657:Histones / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000201:enzymology / Q000473:pathology*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology / Q000473:pathology
D000418:Albumins; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D009363:Neoplasm Proteins; C012589:trichostatin A; D000641:Ammonia