title: Protein kinase C is involved in arsenic trioxide-induced apoptosis and inhibition of proliferation in human bladder cancer cells.
abstract: OBJECTIVE
  Arsenic trioxide (ATO) is a potent antitumor agent used to treat acute promyelocytic leukemia, and recently solid tumors including bladder cancers. However, a mechanism to explain its antitumor activity in bladder cancers is unclear. Here, we investigated the role of protein kinase C (PKC) in ATO-induced apoptosis and inhibition of proliferation in bladder cancer cells.
  
  
  METHODS
  T24 human bladder carcinoma cells were incubated with different concentrations of ATO in the presence or absence of PMA (PKC activator) or H7 (PKC inhibitor). Cell proliferation was assessed by MTT assay, and apoptosis by TUNEL and electron microscopy. Flow cytometry was used to analyze cell cycle distribution, radioimmunoassay to measure PKC activity, and Western blot analysis to detect caspase-3.
  
  
  RESULTS
  ATO inhibited proliferation and induced apoptosis of T24 cells in a dose-dependent manner, caused an increase of percentage of cells in the G(1) phase and a decrease in the S and G(2) phases, and upregulated the expression of activated caspase-3 and reduced PKC activity. These effects were abrogated by PMA, but enhanced by H7.
  
  
  CONCLUSIONS
  PKC is involved in the anticancer activity of ATO for T24 bladder cancer cells, suggesting that targeting the PKC pathway may represent a potential approach to enhance the efficacy of ATO to treat bladder cancers.
authors.affiliation: Department of Urologic Surgery, First Clinical Medical School of Harbin Medical University, Harbin, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Ruihua
authors.initials: R
authors.lastname: An
authors.forename: Xuesong
authors.initials: X
authors.lastname: Dong
authors.forename: Shangha
authors.initials: S
authors.lastname: Pan
authors.forename: Guowen
authors.initials: G
authors.lastname: Duan
authors.forename: Xueying
authors.initials: X
authors.lastname: Sun