Induction of apoptosis and inhibition of telomerase activity by arsenic trioxide (As2O3) in endometrial carcinoma cells

Gynecol Oncol. 2007 Apr;105(1):218-22. doi: 10.1016/j.ygyno.2006.11.027. Epub 2007 Feb 2.

Abstract

Objectives: To examine the effects of arsenic trioxide (As2O3) on human endometrial carcinoma cell lines with respect to cytotoxicity and the induction of apoptosis and telomerase expression in vitro.

Methods: Four endometrial carcinoma cell lines (Ishikawa, ECC-1, RL-95-2 and Hec-1B) were treated with increasing concentrations of As2O3.

Results: As2O3 inhibited proliferation of all cell lines in a concentration and time-dependent manner (IC50 range of 3-7 microM). Coincident with the inhibition of growth, As2O3 also induced apoptosis in all cell lines as measured by the time-dependent increase in M30 antibody fluorescence (binds a caspase-cleaved epitope of cytokeratin 18) detected by flow cytometry, and reduced telomerase activity by decreasing the hTERT mRNA expression.

Conclusion: As2O3 may exert anti-tumor effects through the induction of the apoptosis pathway and telomerase and hTERT may play an important role in the anti-apoptotic effects which are observed when endometrial cancer cells are treated in vitro with As2O3.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Arsenic Trioxide
  • Arsenicals / pharmacology*
  • Cell Growth Processes / drug effects
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Endometrial Neoplasms / drug therapy*
  • Endometrial Neoplasms / enzymology
  • Endometrial Neoplasms / genetics
  • Endometrial Neoplasms / pathology
  • Female
  • Flow Cytometry
  • Humans
  • Oxides / pharmacology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Telomerase / antagonists & inhibitors*
  • Telomerase / biosynthesis
  • Telomerase / genetics

Substances

  • Antineoplastic Agents
  • Arsenicals
  • Oxides
  • RNA, Messenger
  • TERT protein, human
  • Telomerase
  • Arsenic Trioxide