title: The histone deacetylase inhibitor suberoylanilide hydroxamic acid induces growth inhibition and enhances taxol-induced cell death in breast cancer.
abstract: OBJECTIVE
  The histone deacetylase inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA) enhances taxol-induced antitumor effects against some human cancer cells. The aim of this study is to investigate whether SAHA can enhance taxol-induced cell death against human breast cancer cells and to illustrate the mechanism in detail.
  
  
  METHODS
  A panel of eight human breast cancer cell lines and an immortalized human breast epithelial cell line were used to determine the inhibitory effects of SAHA, taxol, or their combination by MTT assay. The effects of SAHA with or without taxol on cell cycle distributions, apoptosis, and protein expressions were also examined. The inhibitory effects on tumor growth were characterized in vivo in BALB/c nude mice bearing a breast cancer xenograft model.
  
  
  RESULTS
  Taxol-resistant and multi-resistant breast cancer cells were as sensitive to SAHA as taxol-sensitive breast cancer cells. A dose-dependent synergistic growth inhibition was found in all the tested breast cancer cell lines treated with the SAHA/taxol combinations. The synergetic effect was also observed in the in vivo xenograft tumor model. The cell cycle analysis and apoptosis assay showed that the synergistic effects resulted from enhanced G2/M arrest and apoptosis.
  
  
  CONCLUSIONS
  SAHA increased the anti-tumor effects of taxol in breast cancer in vitro and in vivo. The combination of SAHA and taxol may have therapeutic potential in the treatment of breast cancer.
authors.affiliation: National Glycoengineering Research Center, Shandong University, No. 44 West Wenhua Road, Jinan, China. shiyikang@sdu.edu.cn
authors.forename: Yi-kang
authors.initials: YK
authors.lastname: Shi
authors.forename: Zhong-hua
authors.initials: ZH
authors.lastname: Li
authors.forename: Xi-qian
authors.initials: XQ
authors.lastname: Han
authors.forename: Ji-hu
authors.initials: JH
authors.lastname: Yi
authors.forename: Zhen-hua
authors.initials: ZH
authors.lastname: Wang
authors.forename: Jing-li
authors.initials: JL
authors.lastname: Hou
authors.forename: Cong-ran
authors.initials: CR
authors.lastname: Feng
authors.forename: Qing-hong
authors.initials: QH
authors.lastname: Fang
authors.forename: Hui-hui
authors.initials: HH
authors.lastname: Wang
authors.forename: Peng-fei
authors.initials: PF
authors.lastname: Zhang
authors.forename: Feng-shan
authors.initials: FS
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Shen
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D017239:Paclitaxel / Q000494:pharmacology*; D014183:Transplantation, Heterologous; D000077337:Vorinostat
chemical_list: D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D000077337:Vorinostat; D017239:Paclitaxel