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Updated: Aug 11, 2026
Differentiation of the SH-SY5Y Human Neuroblastoma Cell Line
Published on: February 17, 2016
Morphological and biochemical changes induced by arsenic trioxide in neuroblastoma cell lines
Kyung-Ha Ryu1, So-Youn Woo, Mi-Young Lee
1Department of Pediatrics and Ewha Medical Research Institute, Ewha Woman's University College of Medicine, Seoul, Korea.
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.
Insights
Arsenic trioxide effectively inhibits neuroblastoma cell growth and induces apoptosis at low concentrations, showing promise for treating this solid tumor. This agent impacts cancer cells before affecting normal lymphocytes, suggesting a therapeutic window.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Arsenic trioxide (As2O3) shows efficacy in hematologic malignancies.
- Limited data exists on As2O3's effects on solid tumors, particularly neuroblastoma.
Purpose of the Study:
- To investigate the growth inhibition and apoptosis induction of As2O3 in neuroblastoma cell lines (SH-SY5Y, SK-N-AS).
- To compare As2O3's effects on neuroblastoma cells versus acute promyelocytic leukemia cells (HL-60) and normal lymphocytes.
Main Methods:
- Cell viability assessed via trypan blue staining.
- Apoptosis evaluated using cell morphology, flow cytometry (annexin-V), and Western blot (bcl-2, PARP).
- Normal peripheral blood lymphocytes examined to determine a safe clinical dose.
Main Results:
- As2O3 (3 microM) significantly inhibited neuroblastoma cell growth and survival before affecting normal lymphocytes.
- Apoptosis markers, including annexin-V positivity and mitochondrial changes, increased with As2O3 concentration and exposure time in neuroblastoma and HL-60 cells.
- Bcl-2 downregulation and PARP degradation were observed across cell lines.
Conclusions:
- Arsenic trioxide demonstrates potent anti-proliferative and pro-apoptotic effects on neuroblastoma cells.
- As2O3 exhibits a favorable therapeutic window, impacting cancer cells at lower concentrations than normal lymphocytes.
- These findings position As2O3 as a promising therapeutic agent for neuroblastoma treatment.
