Morphological and biochemical changes induced by arsenic trioxide in neuroblastoma cell lines

Kyung Ha Ryu, So Youn Woo, Mi Young Lee, Yun Jae Jung, Eun Sun Yoo, Ju Young Seoh, Jeong Hae Kie, Hee Young Shin, Hyo Seop Ahn

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


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 (As2O 3), 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-relafed proteins (bcl-2 and PARP). To decide the dose for the clinical application of AS 2O3, 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 μM 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.

Original languageEnglish
Pages (from-to)609-621
Number of pages13
JournalPediatric Hematology and Oncology
Issue number7
StatePublished - Oct 2005


  • Apoptosis
  • Arsenic trioxide (AsO)
  • Neuroblastoma cell line


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