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Arsenic trioxide is highly cytotoxic to small cell lung carcinoma cells.

Author:
  • Helen Pettersson
  • Alexander Pietras
  • Matilda Thorén
  • Jenny Karlsson
  • Leif Johansson
  • Maria C Shoshan
  • Sven Påhlman
Publishing year: 2009
Language: English
Pages: 160-170
Publication/Series: Molecular Cancer Therapeutics
Volume: 8
Issue: 1
Document type: Journal article
Publisher: American Association for Cancer Research

Abstract english

Small cell lung carcinoma (SCLC) is an extremely aggressive form of cancer and current treatment protocols are insufficient. SCLC have neuroendocrine characteristics and show phenotypical similarities to the childhood tumor neuroblastoma. As multidrug-resistant neuroblastoma cells are highly sensitive to arsenic trioxide (As2O3) in vitro and in vivo, we here studied the cytotoxic effects of As2O3 on SCLC cells. As2O3 induced pronounced cell death in SCLC cells at clinically relevant concentrations, and also at hypoxia. SCLC cells were more sensitive than non-SCLC cells to As2O3. Cell death was mainly due to necrosis, although apoptotic responses were also seen. A significant in vivo effect of As2O3 on SCLC growth was shown in a nude mice-xenograft model, although a fraction of the treated tumor-bearing animals did not respond. The nonresponding SCLC tumors differed in morphology and cell organization compared with treatment-responsive tumors, which in turn, showed decreased vascularization and higher expression of neuroendocrine markers compared with control tumors. Our results suggest a potential clinical application of As2O3 in SCLC therapy. In addition to cell death induction, antiangiogenic induction of differentiation may also be part of the in vivo effect of As2O3 on SCLC growth, as suggested by an increase in neuroendocrine markers in cultured cells.

Keywords

  • Cancer and Oncology

Other

Published
  • Brain Tumor Biology
  • ISSN: 1538-8514
Sven Påhlman
E-mail: sven [dot] pahlman [at] med [dot] lu [dot] se

Professor

Division of Translational Cancer Research

+46 46 222 64 21

MV406 312K1

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