EB1089 induces Skp2-dependent p27 accumulation, leading to cell growth inhibition and cell cycle G1 phase arrest in human hepatoma cells.
EB1089 exhibits a high level of antiproliferative activity against various tumors. However, it is not known whether the mechanism of EB1089 induced the growth inhibition in human hepatic-carcinoma. Here we found that EB1089 significantly reduced cell growth in human hepatoma cells (Hep-G2) and blocked Hep-G2 cell-associated tumor formation in nude mice. The growth inhibition was linked to cell cycle G1 phase arrest by the accumulation of p27 and a reduction of Skp2. Knockdown of Skp2 reversed the p27 induction and G1 arrest. Taken together, our data indicate that EB1089 inhibitory activity is associated with alteration of cell cycle checkpoints through Skp2-dependent p27 induction in Hep-G2 cells.
Luo
Wenjing
W
Department of Occupational and Environmental Health, Faculty of Preventive Medicine, Fourth Military Medical University, Shaanxi, China.
Chen
Yaoming
Y
Liu
Mingchao
M
Du
Kejun
K
Zheng
Gang
G
Cai
Tongjian
T
Zhang
Wenbin
W
Zhao
Fang
F
Yao
Ting
T
Yang
Ruihua
R
Chen
Jingyuan
J
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism*; D016193:G1 Phase / Q000187:drug effects*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044786:S-Phase Kinase-Associated Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D044786:S-Phase Kinase-Associated Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D002117:Calcitriol; C078903:seocalcitol