title: Apoptosis of bladder cancer by sodium butyrate and cisplatin.
abstract: The effects of sodium butyrate (SB), a histone deacetylase inhibitor, in combination with cisplatin (CDDP), for inhibition of cell growth and induction of apoptosis were investigated in bladder cancer cell lines in vitro. Bladder cancer cell lines T24, 253J, and UMUC3 were treated with different concentrations of CDDP or SB. Cell proliferation was studied by XTT assay. Cell-cycle analysis and induction of apoptosis were analyzed by laser scanning cytometry (LSC). Western blot analysis was used to determine expression of p21, p27, TRADD, FADD, caspase-2, and caspase-7. We observed that SB in combination with CDDP induced significant inhibition of cell growth in a dose-dependent manner through G₁ arrest and apoptosis, as determined by LSC. When bladder cancer cell lines were treated with SB plus CDDP, Western blotting showed increased expression of p21 but not p27 in T24 cells, whereas both p21 and p27 increased in 253J and UMUC3 cells. All cell lines exhibited a moderate increase in TRADD and decrease in procaspase-2 but no significant change in FADD and procaspase-7. The results showed the synergistic anticancer effect of SB in combination with CDDP, their potential for treatment of bladder cancer, and their mechanism of action in terms of cell signal transduction and induction of apoptosis.
authors: The Department of Urology, Hyogo College of Medicine, 1-1 Mukogawacho, Nishinomiya, Hyogo 663-8501, Japan.
authors: Takuo
authors: T
authors: Maruyama
authors: Shingo
authors: S
authors: Yamamoto
authors: Jun
authors: J
authors: Qiu
authors: Yasuo
authors: Y
authors: Ueda
authors: Toru
authors: T
authors: Suzuki
authors: Michio
authors: M
authors: Nojima
authors: Hiroki
authors: H
authors: Shima
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002087:Butyrates / Q000008:administration & dosage / Q000494:pharmacology*; D053143:Caspase 2 / Q000096:biosynthesis; D053179:Caspase 7 / Q000096:biosynthesis; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004357:Drug Synergism; D006801:Humans; D015854:Up-Regulation / Q000187:drug effects; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*
chemical_list: D002087:Butyrates; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases; D053143:Caspase 2; D053179:Caspase 7; D002945:Cisplatin