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HISTONE DEACETYLASE INHIBITOR, TRICHOSTATIN A, MODULATE EXPRESSIONS OF CELL CYCLE REGULATORY PROTEIN AND TUMOR SUPPRESSOR GENES IN PROSTATE CANCER CELLS
Author(s) -
Kim Hee Jin,
Kim Hyung Sik
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a39-a
Subject(s) - trichostatin a , lncap , cell cycle , cyclin d1 , cancer research , histone deacetylase , cyclin d , histone deacetylase inhibitor , cancer cell , cell growth , cyclin a , prostate cancer , cyclin b , chemistry , biology , apoptosis , cancer , histone , biochemistry , gene , genetics
Histone deacetylase (HDAC) inhibitors have been reported to induce apoptosis and cell cycle arrest. However, the effect of the HDAC inhibitor, trichostatin A (TSA), on prostate cancer cells has not been fully understood. The aim of this study was to investigate the expression patterns of genes responsible for the cell cycle regulation in prostate cancer cell lines treated with TSA. Induction of apoptosis was measured in prostate cancer cells treated with at various concentrations of TAS. Changes in the expression of cell cycle regulatory proteins (cyclin D1, cyclin E, CDK2, CDK4, and pRB) and tumor suppressor genes (p16 and WT‐1) were also assessed. TSA inhibited the proliferation of prostate cancer cells at much lower concentrations, where 1.0 uM TSA was completely inhibited the LNCaP cells growth. DAPI staining data confirmed the apoptotic cells of LNCaP following 24 h of TSA (50 nM) treatment. TSA slightly decreased the expression of cyclin D1 and CDK2 in DU‐145 cells, but no change was observed in DU‐145 cells. Western blotting analyses revealed a dramatic increase in the level of H3 and H4 acetylation after TSA treatment. Cell cycle analysis showed that TSA decreased the proportion of cells in S phase and increased the proportion of cells in G1 and G2 phases. These results suggested that TSA may have a different mechanism of action for anti‐tumor activity in prostate cancer cell lines.