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G1 Arrest of U937 Human Monocytic Leukemia Cells by Sodium Butyrate, an HDAC Inhibitor, Via Induction of Cdk Inhibitors and Down-regulation of pRB Phosphorylation

Cdk inhibitors의 발현 증가 및 pRB 인산화 저해에 의한 HDAC inhibitor인 sodium butyrate에 의한 인체백혈병세포의 G1 arrest유발

  • Choi, Yung-Hyun (Department of Biochemistry, Dongeui University College of Oriental Medicine and Department of Biomaterial Control, Dongeui University)
  • 최영현 (동의대학교 한의과대학 생화학교실 및 대학원 바이오물질제어학과)
  • Published : 2009.07.30

Abstract

We investigated the effects of sodium butyrate, a histone deacetylase inhibitor, on the cell cycle progression in human monocytic leukemia U937 cells. Exposure of U937 cells to sodium butyrate resulted in growth inhibition, G1 arrest of the cell cycle and induction of apoptosis in a dose-dependent manner as measured by MTT assay and flow cytometry analysis. The increase in G1 arrest was associated with the down-regulation in cyclin D1, E, A, cyclin-dependent kinase (Cdk) 4 and 6 expression, and up-regulation of Cdk inhibitors such as p21 and p27. Sodium butyrate treatment also inhibited the phosphorylation of retinoblastoma protein (pRB) and p130, however, the levels of transcription factors E2F-1 and E2F-4 were not markedly modulated. Furthermore, the down-regulation of phosphorylation of pRB and p130 by this compound was associated with enhanced binding of pRB and E2F-1, as well as p130 and E2F-4, respectively. Overall, the present results demonstrate a combined mechanism involving the inhibition of pRBjp130 phosphorylation and induction of Cdk inhibitors as targets for sodium butyrate that may explain some of its anti-cancer effects in U937 cells.

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