Korean J Pediatr Hematol Oncol.  2003 Apr;10(1):64-71.

Antitumor Effects of Arsenic Trioxide on Neuroblastoma

Affiliations
  • 1Department of Pediatrics, Ewha Womans Unversity College of Medicine, Seoul, Korea.
  • 2Department of Microbiology, Ewha Womans Unversity College of Medicine, Seoul, Korea.
  • 3Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
  • 4Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea. hsahn@snu.ac.kr

Abstract

PURPOSE
We aimed to study the feasibility of arsenic trioxide as a treatment of neuroblastoma which has the ability to differentiate into nonmalignant cells like acute promyelocytic leukemia. METHODS: To determine the effects of arsenic trioxide in various concentrations and exposure time on the survivial of neuroblastoma cell lines, SH-SY5Y and SK-N-AS cells were cultured in RPMI 1640 media with 1 to 20muM concentration of arsenic trioxide. Apoptosis was measured with flow cytometry by staining with 7-aminoactinomycin D. Cell cycle was assessed by monitoring the DNA contents by flow cytometry. Arsenic trioxide induced cell morphologic changes were also observed with May-Grunwald-Giemsa stain under a light microscope. RESULTS: Arsenic trioxide induced apoptosis in SH-SY5Y cells earlier in the same concentration and to a more severe degree with the same exposure time than in HL-60 cells. The apoptosis induced by arsenic trioxide was steeply increased to 79.3 10.1% at 24 hours and then maintained a plateau on 20muM concentration, while increasing steadily to 40.2 6.5% until 72 hours on 5muM concentration. The proliferating cell proportion in S/G2/M phase was decreased with arsenic trioxide concentration and with exposure time in both SH-SY5Y and HL-60 cells, especially more so with the SH-SY5Y cells. The cellularity was decreased and more apoptotic cells could be observed in the arsenic trioxide treatment group than in untreated control group. CONCLUSION: As in acute promyelocytic leukemic cells, arsenic trioxide induced apoptosis and cell cycle arrest of proliferating phase in neuroblastoma cells.

Keyword

Arsenic trioxide; Apoptosis; Cell cycle; Neuroblastoma

MeSH Terms

Apoptosis
Arsenic*
Cell Cycle
Cell Cycle Checkpoints
Cell Line
DNA
Flow Cytometry
HL-60 Cells
Humans
Leukemia, Promyelocytic, Acute
Neuroblastoma*
Arsenic
DNA
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