Related Experiment Video
Updated: Jun 11, 2026
Cellular Toxicity of Nanogenomedicine in MCF-7 Cell Line: MTT assay
Published on: April 3, 2009
Arsenic trioxide promotes mitochondrial DNA mutation and cell apoptosis in primary APL cells and NB4 cell line
Ran Meng1, Jin Zhou2, Meng Sui3
1Division of Neurology, the Ninth Clinical Medical College of Beijing University (Shijitan Hospital), Beijing, 100038, China. victor65@126.com.
Abstract:
This study aimed to investigate the effects of arsenic trioxide (As(2)O(3)) on the mitochondrial DNA (mtDNA) of acute promyelocytic leukemia (APL) cells. The NB4 cell line was treated with 2.0 micromol/L As(2)O(3) in vitro, and the primary APL cells were treated with 2.0 micromol/L As(2)O(3) in vitro and 0.16 mg kg(-1) d(-1) As(2)O(3) in vivo. The mitochondrial DNA of all the cells above was amplified by PCR, directly sequenced and analyzed by Sequence Navigatore and Factura software. The apoptosis rates were assayed by flow cytometry. Mitochondrial DNA mutation in the D-loop region was found in NB4 and APL cells before As(2)O(3) use, but the mutation spots were remarkably increased after As(2)O(3) treatment, which was positively correlated to the rates of cellular apoptosis, the correlation coefficient: r (NB4-As2O3)=0.973818, and r (APL-As2O3)=0.934703. The mutation types include transition, transversion, codon insertion or deletion, and the mutation spots in all samples were not constant and regular. It is revealed that As(2)O(3) aggravates mtDNA mutation in the D-loop region of acute promyelocytic leukemia cells both in vitro and in vivo. Mitochondrial DNA might be one of the targets of As(2)O(3) in APL treatment.
Insights
Arsenic trioxide (As2O3) treatment significantly increases mitochondrial DNA (mtDNA) mutations in acute promyelocytic leukemia (APL) cells. This aggravation of mtDNA mutations correlates with increased cellular apoptosis, suggesting mtDNA as a potential therapeutic target.
Area of Science:
- Hematology
- Molecular Biology
- Toxicology
Background:
- Acute promyelocytic leukemia (APL) is a distinct subtype of leukemia.
- Arsenic trioxide (As2O3) is a known therapeutic agent for APL.
- Mitochondrial DNA (mtDNA) plays a crucial role in cellular function and apoptosis.
Purpose of the Study:
- To investigate the impact of As2O3 on mtDNA in APL cells.
- To determine if As2O3 induces or exacerbates mtDNA mutations.
- To explore the relationship between mtDNA mutations and apoptosis in APL.
Main Methods:
- NB4 and primary APL cells were treated with As2O3 in vitro and in vivo.
- Mitochondrial DNA was amplified using PCR and sequenced.
- Apoptosis rates were analyzed by flow cytometry.
- Sequence analysis was performed using specialized software.
Main Results:
- As2O3 treatment led to a significant increase in mtDNA mutations in the D-loop region of APL cells.
- The observed increase in mtDNA mutations showed a strong positive correlation with elevated apoptosis rates.
- Mutation types included transitions, transversions, and insertions/deletions, with irregular mutation spot distribution.
Conclusions:
- As2O3 aggravates mtDNA mutations in the D-loop region of APL cells, both in vitro and in vivo.
- mtDNA mutations may be a significant factor in As2O3-induced apoptosis in APL.
- Mitochondrial DNA is identified as a potential molecular target for As2O3 in APL treatment.
