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Morphological and biochemical changes induced by arsenic trioxide in neuroblastoma cell lines
Cited 11 time in
Web of Science
Cited 12 time in Scopus
- Authors
- Issue Date
- 2005-09-17
- Publisher
- Taylor & Francis
- Citation
- Pediatr Hematol Oncol. 2005 Oct-Nov;22(7):609-21.
- Keywords
- Annexin A5/biosynthesis ; Antineoplastic Agents/*pharmacology/therapeutic use ; Apoptosis/*drug effects ; Arsenicals/*pharmacology/therapeutic use ; Cell Survival/drug effects ; Collagen Type XI/biosynthesis ; Dose-Response Relationship, Drug ; Down-Regulation/drug effects ; Gene Expression Regulation, Neoplastic/drug effects ; HL-60 Cells ; Humans ; Lymphocytes/metabolism/ultrastructure ; Neuroblastoma/drug therapy/*metabolism/ultrastructure ; Oxides/*pharmacology/therapeutic use ; Proto-Oncogene Proteins c-bcl-2/biosynthesis
- Abstract
- Arsenic trioxide has recently been shown to inhibit growth and induce apoptosis in a variety of hematologic malignancies, but very little is known about its effects on solid tumors and especially on neuroblastoma cells that have self-differentiating characteristics. To demonstrate the growth inhibition induced in neuroblastoma cells (the SH-SY5Y and SK-N-AS cell line) and acute promyelocytic leukemia cells (HL-60) by arsenic trioxide (As2O3), the viable cell numbers were counted after trypan blue staining. Apoptosis was assessed by the cell morphology, by flow cytometry with annexin-V staining, and by Western blot analysis for the apoptosis-related proteins (bcl-2 and PARP). To decide the dose for the clinical application of As2O3, normal peripheral blood lymphocytes were also examined. The growth and survival of the SH-SY5Y and SK-N-AS cells were markedly inhibited by As2O3 treatment at a 3 microM concentration before the changes of the normal lymphocytes were observed. The apoptotic cells showed a shrunken cell nucleus, and an increase in the number and balloon-like swelling of the mitochondria at 72 h after the As2O3 was added. Apoptosis of the annexin-V-positive cell proportion in the neuroblastoma cell lines was increased with increasing the exposure time and the concentration of As2O3, just like the HL-60 cells. Bcl-2 downregulation and PARP degradation were also noted all the cell lines, but these changes were not statistically significant among the 3 cell lines. Taken together, these results indicate that As2O3 is an excellent candidate as a therapeutic agent for the treatment of neuroblastoma.
- ISSN
- 0888-0018 (Print)
- Language
- English
- URI
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16166054
https://hdl.handle.net/10371/29395
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