Sodium butyrate regulates androgen receptor expression and cell cycle arrest in human prostate cancer cells.
Histone deacetylase (HDAC) inhibitors have been shown to modify the expression of a variety of genes related to cell cycle regulation and apoptosis in several cancer cells. However, the precise mode of action of HDAC inhibitors in prostate cancer cells is not completely understood. This study examined whether an HDAC inhibitor affects cell death in human prostate cancer cells through the epigenetic regulation of androgen receptor (AR) expression. The molecular mechanism of the HDAC inhibitor, sodium butyrate, on the epigenetic alterations of cell cycle regulators was evaluated in androgen-dependent human prostate cancer LNCaP cells. The expression levels of acetylated histone H3 and H4 increased significantly after 48 h treatment with sodium butyrate. Sodium butyrate induced the expression of AR after 48 h treatment. In addition, immunofluorescence assay revealed the nuclear localization of the AR after sodium butyrate treatment. Sodium butyrate also significantly decreased the expression of the cell cycle regulatory proteins (cyclin D1/cyclin dependent kinase (CDK)4, CDK6, and cyclin E/CDK2) in the LNCaP cells after 48 h treatment. Furthermore, p21Waf1/Cip1 and p27Kip1 were upregulated as a result of the sodium butyrate treatment. These results suggest that sodium butyrate effectively inhibited cell proliferation and induced apoptosis of human prostate cancer cells by altering the expression of cell cycle regulators and AR. This study indicated that sodium butyrate may be a potential agent in prostate cancer treatment.
Kim
Jeonga
J
Laboratory of Molecular Toxicology and 3Brain Korea 21 Project Team, College of Pharmacy, Pusan National University, San 30, Jangiun-dong, Gumjung-ku, Busan, South Korea.
Park
Hyeyoung
H
Im
Ji Young
JY
Choi
Wahn Soo
WS
Kim
Hyung Sik
HS
D000107:Acetylation / Q000187:drug effects; D000728:Androgens / Q000502:physiology; D002087:Butyrates / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000096:biosynthesis; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D008297:Male; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017430:Prostate-Specific Antigen / Q000096:biosynthesis; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011944:Receptors, Androgen / Q000096:biosynthesis*
D000728:Androgens; D002087:Butyrates; D018797:Cell Cycle Proteins; D006657:Histones; D011944:Receptors, Androgen; D017430:Prostate-Specific Antigen