Arsenic trioxide induces apoptosis in cisplatin-sensitive and -resistant ovarian cancer cell lines

Int J Gynecol Cancer. 2005 Sep-Oct;15(5):872-7. doi: 10.1111/j.1525-1438.2005.00251.x.

Abstract

Arsenic trioxide (As(2)O(3)), has been used for centuries in traditional Chinese medicine; it has considerable efficacy in the treatment of relapsed acute promyelocytic leukemia, inducing partial differentiation and promoting apoptosis of malignant promyelocytes. Although a number of studies have demonstrated that As(2)O(3) has potent activity against cell growth in a series of leukemia cell lines, little information is available regarding this compound's effect on cell growth in solid tumor cell lines. In this study, we investigated the effects of As(2)O(3)in vitro on ovarian cancer cell lines sensitive (3AO) and resistant (3AO/CDDP) to cisplatin. The 3-(4,5-dimethy-thiazoyl-2-yl)-2,5-diphenyl-tetrazolium bromide assay was used to evaluate cytotoxicity. Flow cytometric analysis was used to determine the apoptosis, cell cycle distribution. We clearly demonstrated that As(2)O(3) induced cell apoptosis and inhibition of cell growth in both the cell lines. Furthermore, we identified that As(2)O(3)-induced apoptosis involved Fas pathway. As(2)O(3) is an active agent against ovarian cancer cells and could be effective in the clinical treatment of ovarian cancer.

MeSH terms

  • Apoptosis / drug effects*
  • Arsenic Trioxide
  • Arsenicals / pharmacology*
  • Cell Line, Tumor
  • Cisplatin / pharmacology*
  • Drug Resistance, Neoplasm*
  • Female
  • Humans
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology*
  • Oxides / pharmacology*
  • Signal Transduction / drug effects
  • fas Receptor / metabolism

Substances

  • Arsenicals
  • Oxides
  • fas Receptor
  • Cisplatin
  • Arsenic Trioxide