Antitumor Effects of Arsenic Trioxide on Neuroblastoma.
- Author:
Kyung Ha RYU
1
;
So Youn WOO
;
Ju Young SEOH
;
Chong Jai KIM
;
Hee Young SHIN
;
Hyo Seop AHN
Author Information
1. Department of Pediatrics, Ewha Womans Unversity College of Medicine, Seoul, Korea.
- Publication Type:Original Article
- Keywords:
Arsenic trioxide;
Apoptosis;
Cell cycle;
Neuroblastoma
- MeSH:
Apoptosis;
Arsenic*;
Cell Cycle;
Cell Cycle Checkpoints;
Cell Line;
DNA;
Flow Cytometry;
HL-60 Cells;
Humans;
Leukemia, Promyelocytic, Acute;
Neuroblastoma*
- From:Korean Journal of Pediatric Hematology-Oncology
2003;10(1):64-71
- CountryRepublic of Korea
- Language:Korean
-
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.
