title: Growth of human prostate cancer cells is significantly suppressed in             vitro with sodium butyrate through apoptosis.
abstract: Histone deacetylase inhibitors (HDACis) have shown significant antiproliferative             and apoptotic properties in various types of cancer cells, including prostate             cancer cells, and are therefore being evaluated as a treatment modality. However,             the mechanism by which sodium butyrate (SB) induces apoptosis is not completely             understood. We focused on SB which exists in the intestine and is therefore expected             to have less adverse effects. In this study, three prostate cancer cell lines             (LNCaP, DU145 and PC-3) were treated in vitro with different concentrations of             SB. Cell proliferation was studied by the XTT assay; cell cycle analysis and induction             of apoptosis were studied by laser scanning cytometry. Western blot analysis was             used to study p21, p27, CDK2, CDK4, CDK6, caspase-3, caspase-7, Fas, FADD, TRADD,             Bcl-2 and Bax protein expression. SB inhibited cell growth and induced apoptosis             in a concentration-dependent manner in human prostate cancer cells (LNCaP, DU145             and PC-3). Western blot analysis showed dose-dependent increases of p21 levels             in DU145 and PC-3 cells, and dose-dependent decreases of CDK2, CDK4, CDK6 and             procaspase-3 protein levels in all three prostate cancer cell lines. Bcl-xL was             significantly down-regulated in DU145 cells, and Bcl-2 was significantly down-regulated             in PC-3 and LNCaP cells. No significant changes were observed in procaspase-7,             TRADD and Bax expression, although slight decreases in Fas and FADD expression             were seen in all three prostate cancer cell lines. Analysis of cell morphology             using laser scanning microscopy detected condensed and fragmented nuclei. In conclusion,             SB induces G1 and G2 arrest by increasing p21 expression resulting in CDK2, CDK4             and CDK6 down-regulation. SB potently induced apoptosis, which was accompanied             by DNA fragmentation, down-regulated Bcl-2 in LNCaP and PC-3 cells, Bcl-xL in             DU145 cells, and down-regulated procaspase-3, but not procaspase-7, in these human             prostate cancer cell lines. These results suggest that SB may serve as a new modality             for the treatment of hormone refractory prostate cancer.
authors.affiliation: Department of Blood Purification Center, Yantai Yuhuangding Hospital, Qingdao University Medical College, Yantai 264000, Shandong Province, PR China. qiujun536@hotmail.com
authors.forename: Jun
authors.initials: J
authors.lastname: Qiu
authors.forename: Zhenli
authors.initials: Z
authors.lastname: Gao
authors.forename: Hiroki
authors.initials: H
authors.lastname: Shima
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002087:Butyrates / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal; D011471:Prostatic Neoplasms / Q000378:metabolism*
chemical_list: D002087:Butyrates; D056572:Histone Deacetylase Inhibitors