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

Pettersson, Helen LU ; Pietras, Alexander LU ; Thorén, Matilda LU ; Karlsson, Jenny LU ; Johansson, Leif LU ; Shoshan, Maria C and Påhlman, Sven LU (2009) In Molecular Cancer Therapeutics 8(1). p.160-170
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Molecular Cancer Therapeutics
volume
8
issue
1
pages
160 - 170
publisher
American Association for Cancer Research
external identifiers
  • wos:000262497100019
  • pmid:19139125
  • scopus:58149498185
ISSN
1538-8514
DOI
10.1158/1535-7163.MCT-08-0595
language
English
LU publication?
yes
id
1dd77707-c732-4167-b1e2-4f73518952d8 (old id 1289772)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19139125?dopt=Abstract
date added to LUP
2009-02-04 10:55:40
date last changed
2017-08-06 04:44:03
@article{1dd77707-c732-4167-b1e2-4f73518952d8,
  abstract     = {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.},
  author       = {Pettersson, Helen and Pietras, Alexander and Thorén, Matilda and Karlsson, Jenny and Johansson, Leif and Shoshan, Maria C and Påhlman, Sven},
  issn         = {1538-8514},
  language     = {eng},
  number       = {1},
  pages        = {160--170},
  publisher    = {American Association for Cancer Research},
  series       = {Molecular Cancer Therapeutics},
  title        = {Arsenic trioxide is highly cytotoxic to small cell lung carcinoma cells.},
  url          = {http://dx.doi.org/10.1158/1535-7163.MCT-08-0595},
  volume       = {8},
  year         = {2009},
}