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ORIGINAL ARTICLES Cellular and Molecular Biology

EB1089 Induces Skp2-Dependent p27 Accumulation, Leading to Cell Growth Inhibition and Cell Cycle G1 Phase Arrest in Human Hepatoma Cells

, , , , , , , , , & show all
Pages 29-37 | Published online: 11 Jun 2009
 

Abstract

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.

ABBREVIATIONS
FBS=

fetal bovine serum

Skp2=

S-phase kinase-associated protein

EB1089=

22, 24-diene-24a, 26a,27a-trihomo-1-, 25-dihydroxy-vitamin D3

Hep-G2=

human hepatocarcinoma cells

ABBREVIATIONS
FBS=

fetal bovine serum

Skp2=

S-phase kinase-associated protein

EB1089=

22, 24-diene-24a, 26a,27a-trihomo-1-, 25-dihydroxy-vitamin D3

Hep-G2=

human hepatocarcinoma cells

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