title: Dipyrithione induces cell-cycle arrest and apoptosis in four cancer cell lines in vitro and inhibits tumor growth in a mouse model.
abstract: BACKGROUND
  Dipyrithione (PTS2) is widely used as a bactericide and fungicide. Here, we investigated whether PTS2 has broad-spectrum antitumor activity by studying its cytotoxicity and proapoptotic effects in four cancer cell lines.
  
  
  METHODS
  We used MTT assays and trypan blue staining to test the viability of cancer cell lines. Hoechst 33258 and DAPI staining were used to observe cell apoptosis. Cell-cycle percentages were analyzed by flow cytometry. Apoptosis was assayed using caspase-3 and poly (ADP-ribose) polymerase (PARP) combined with Western blotting. Student's t-test was used for statistical analysis.
  
  
  RESULTS
  PTS2 inhibited proliferation in four cancer cell lines in a dose-dependent manner. Treated cells showed shrinkage, irregular fragments, condensed and dispersed blue fluorescent particles compared with control cells. PTS2 induced cycle-arrest and death. Cleavage of caspase-9, caspase-3, and PARP were detected in PTS2-treated cells. Antitumor activity of PTS2 was more effective against widely used cancer drugs and its precursor.
  
  
  CONCLUSIONS
  PTS2 appears to have novel cytotoxicity and potent broad-spectrum antitumor activity, which suggests its potential as the basis of an anticancer drug.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Fan
authors.forename: Caizhi
authors.initials: C
authors.lastname: Liu
authors.forename: Yongmao
authors.initials: Y
authors.lastname: Huang
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Linlin
authors.initials: L
authors.lastname: Cai
authors.forename: Shengnan
authors.initials: S
authors.lastname: Wang
authors.forename: Yongze
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: The Key Lab of Animal Physiology, College of Life Science, Hebei Normal University, Hebei Province, Shijiazhuang 050024, China. xlduan0311@163.com.
authors.forename: Xianglin
authors.initials: X
authors.lastname: Duan
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Yin
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D020014:K562 Cells; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D015394:Molecular Structure; D011725:Pyridines / Q000494:pharmacology*; D020298:U937 Cells; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D011725:Pyridines; C032196:dipyrithione