ZBP-89 reduces the cell death threshold in hepatocellular carcinoma cells by increasing caspase-6 and S phase cell cycle arrest.
ZBP-89 inhibits the some tumor cells but its role in HCC is unknown. We investigated effect of ZBP-89 on cell death of 5 HCC cell lines with different status of p53. We found that ZBP-89 significantly induced cell death of all HCC cells particularly those with wild-type p53. The inhibition was well correlated with the induction of caspase-6 activity. The inhibition of caspase-6 abolished the effect of ZBP-89. ZBP-89 reduced the cells in G2-M but increased them in S phase. With the changes in caspase-6 and cell cycle, ZBP-89 greatly enhanced the killing effectiveness of 5-fluorouracil or staurosporine in HCC cells.
Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong. gchen@cuhk.edu.hk
George G
GG
Chen
Ursula P F
UP
Chan
Long-Chuan
LC
Bai
King Yip
KY
Fung
Art
A
Tessier
Ann K Y
AK
To
Juanita L
JL
Merchant
Paul B S
PB
Lai
D000970:Antineoplastic Agents / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D053178:Caspase 6 / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005434:Flow Cytometry; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D016196:S Phase / Q000187:drug effects / Q000502:physiology*; D019311:Staurosporine / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism*
D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D014157:Transcription Factors; C110951:ZNF148 protein, human; D053178:Caspase 6; D019311:Staurosporine; D005472:Fluorouracil