Arsenic trioxide is highly cytotoxic to small cell lung carcinoma cells.
Mol Cancer Ther. 2009 Jan;8(1):160-70
Authors: Pettersson HM, Pietras A, Munksgaard Persson M, Karlsson J, Johansson L, Shoshan MC, Påhlman S
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 (As(2)O(3)) in vitro and in vivo, we here studied the cytotoxic effects of As(2)O(3) on SCLC cells. As(2)O(3) 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 As(2)O(3). Cell death was mainly due to necrosis, although apoptotic responses were also seen. A significant in vivo effect of As(2)O(3) 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 As(2)O(3) in SCLC therapy. In addition to cell death induction, antiangiogenic induction of differentiation may also be part of the in vivo effect of As(2)O(3) on SCLC growth, as suggested by an increase in neuroendocrine markers in cultured cells. [Mol Cancer Ther 2009;8(1):160-70].
PMID: 19139125 [PubMed - in process]