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. 2006 Jun;3(2):136-40.
doi: 10.3390/ijerph2006030017.

Dose- and time-dependent response of human leukemia (HL-60) cells to arsenic trioxide treatment

Clement G Yedjou  1 , Pamela Moore, Paul B Tchounwou
Affiliations

Dose- and time-dependent response of human leukemia (HL-60) cells to arsenic trioxide treatment

Clement G Yedjou et al. Int J Environ Res Public Health. 2006 Jun.

Abstract

The treatment of acute promyelocytic leukemia (APL) has been based on the administration of all-trans retinoic acid plus anthracycline chemotherapy, which is very effective as first line therapy; however 25 to 30% of patients will relapse with their disease becoming refractory to conventional therapy. Recently, studies have shown arsenic trioxide to be effective in the treatment of acute promyelocytic leukemia. In this study, we used the human leukemia (HL-60) cell line as a model to evaluate the cytoxicity of arsenic trioxide based on the MTT assay. Data obtained from this assay indicated that arsenic trioxide significantly reduced the viability of HL-60 cells, showing LD50 values of 14.26 + 0.5microg/mL, 12.54 + 0.3microg/mL, and 6.4 + 0.6microg/mL upon 6, 12, and 24 hours of exposure, respectively; indicating a dose- and time-dependent response relationship. Findings from the present study indicate that arsenic trioxide is highly cytotoxic to human leukemia (HL-60) cells, supporting its use as an effective therapeutic agent in the management of acute promyelocytic leukemia.

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Figures

Figure 1
Figure 1
Toxicity of arsenic trioxide to human leukemia (HL-60) cells. HL-60 cells were cultured with different doses of arsenic trioxide for 6 hours as indicated in the Materials and Methods. Cell viability was determined based on the MTT assay. Each point represents a mean value and standard deviation of 3 experiments with 6 replicates per dose. Cell Viability in 10 and 20 μg/mL are significantly different (p < 0.05) compared to the control according to ANOVA Dunnett’s test.
Figure 2
Figure 2
Toxicity of arsenic trioxide to human leukemia (HL-60) cells. HL-60 cells were treated with different doses of arsenic trioxide for 12 hours as indicated in the Materials and Methods. Cell viability was determined based on the MTT assay. Each point represents a mean value and standard deviation of 3 experiments with 6 replicates per concentration. Cell Viability in 5, 10, and 20 μg/mL are significantly different (p < 0.05) compared to the control according to ANOVA Dunnett’s test.
Figure 3
Figure 3
Toxicity of arsenic trioxide to human leukemia (HL-60) cells. HL-60 cells were cultured with different doses of arsenic trioxide for 24 hours as indicated in the Materials and Methods. Cell viability was determined based on the MTT assay. Each point represents a mean value and standard deviation of 3 experiments with 6 replicates per dose. All values are significantly different (p < 0.05) compared to the control cells according to ANOVA Dunnett’s test, except 0.04–0.08 μg/mL.
Figure 4
Figure 4
Time-response relationship with regard to the cytotoxicity of arsenic trioxide to human leukemia (HL-60) cells. HL-60 cells were cultured with different doses of arsenic trioxide for 6, 12, and 24 hours respectively as indicated in the Materials and Methods. Cell viability was determined based on the MTT assay. Each point represents a mean ± SD of 3 experiments with 6 replicates per dose.
Figure 5
Figure 5
Time-response relationship with regard to the LD50 values of arsenic trioxide to human leukemia (HL-60) cells. LD50 = 14.26 ± 0.5 μg/mL for 6 h; 12.54 ± 0.3 μg/mL for 12 h; and 6.35 ± 0.6 μg/mL for 24 h of exposure.
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