title: Antiproliferative and anti-invasive effects of inorganic and organic arsenic compounds on human and murine melanoma cells in vitro.
abstract: OBJECTIVE
  For patients with advanced melanoma, no treatment options are available at present that provide either sufficient response rates or a significant prolongation of overall survival. The present study examines the effects of two inorganic and six organic arsenic compounds on cell proliferation and cell invasion of melanoma cells in vitro.
  
  
  METHODS
  The effects of arsenic compounds on proliferation of human melanoma A375 cells and murine melanoma B16F10 cells were examined by MTT assay and 5-bromo-2'-deoxyuridine (BrdU) incorporation assay, and the effects of the compounds on cell invasion were examined by the Boyden chamber invasion assay. The amounts of active matrix metalloproteinase (MMP)-2 and pro-MMP-2 in the culture supernatant of A375 cells were determined by an MMP-2 activity assay system.
  
  
  RESULTS
  Arsenate and arsenic trioxide (As(2) O(3) ) inhibited the proliferation of A375 and B16F10 cells significantly at concentration ranges of 0.1-20µg/ml (P<0.001), while the organic compounds arsenobetaine, arsenocholine, dimethylarsinic acid, methylarsonic acid, tetramethylarsonium and trimethylarsine oxide did not show any inhibitory effects even at 20µg/ml. Cell invasion of A375 and B16F10 cells through a layer of collagen IV was significantly inhibited by 0.1-20 µg/ml of arsenate or As(2) O(3) (P<0.05), while the organic compounds did not inhibit cell invasion. Arsenate or As(2) O(3) at 0.2-10µg/ml significantly inhibited the amount of active MMP-2 and pro-MMP-2 secreted into the A375 cell culture supernatant (P<0.05).
  
  
  CONCLUSIONS
  Our findings show that the inorganic arsenic compounds arsenate and As(2) O(3) inhibit cell proliferation and prevent the invasive properties of melanoma cells, possibly by decreasing MMP-2 production from the cells.
authors.affiliation: Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Hiwatashi
authors.forename: Hiroko
authors.initials: H
authors.lastname: Tadokoro
authors.forename: Kayo
authors.initials: K
authors.lastname: Henmi
authors.forename: Mariko
authors.initials: M
authors.lastname: Arai
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Kaise
authors.forename: Sachiko
authors.initials: S
authors.lastname: Tanaka
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Hirano
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001151:Arsenic / Q000494:pharmacology* / Q000627:therapeutic use; D001152:Arsenicals / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D024141:Collagen Type IV; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D008545:Melanoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D009361:Neoplasm Invasiveness / Q000517:prevention & control
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D024141:Collagen Type IV; D020778:Matrix Metalloproteinase 2; D001151:Arsenic