The preclinical activity of the histone deacetylase inhibitor PXD101 (belinostat) in hepatocellular carcinoma cell lines.
The activity of the histone deacetylase inhibitor PXD101 was investigated in three hepatocellular carcinoma (HCC) cell lines. PXD101 was found to inhibit cell growth at a dose-dependent manner and induce histone acetylation in PLC/PRF/5, Hep3B and HepG2 cells. In PLC/PRF/5 and Hep3B cells which express hepatitis B-related genes (HBx, HBc and HBc), treatment with PXD101 resulted in apoptosis without a significant effect on viral gene expression. Exposure to PXD101 for up to 48 h had varying effects on the expression of 12 cellular genes with tumor suppressor functions, including p21, SOCS1, CMTM5, RASAL1, DLEC1, SFRP (-1, -2, -4 and -5), ADAMTS (-8 and -9). This study provided the basis for a phase II clinical trial of PXD101 in inoperable hepatitis-B associated HCC.
Ma
Brigette B Y
BB
State Key Laboratory in Oncology in South China, Sir YK Pao Centre for Cancer, Department of Clinical Oncology, Hong Kong Cancer Institute, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China. brigette@clo.cuhk.edu.hk
Sung
Fion
F
Tao
Qian
Q
Poon
Fan Fong
FF
Lui
Vivian W
VW
Yeo
Winnie
W
Chan
Stephen L
SL
Chan
Anthony T C
AT
D000107:Acetylation / Q000187:drug effects; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006657:Histones / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013449:Sulfonamides; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D012333:RNA, Messenger; D013449:Sulfonamides; D025521:Tumor Suppressor Proteins; C487081:belinostat