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Arsenic trioxide-mediated oxidative stress and genotoxicity in human hepatocellular carcinoma cells.

Alarifi S, Ali D, Alkahtani S, Siddiqui MA, Ali BA - Onco Targets Ther (2013)

Bottom Line: Arsenic trioxide elicited a significant (P < 0.01) reduction in glutathione (15.67% and 26.52%), with a concomitant increase in malondialdehyde level (67.80% and 72.25%; P < 0.01), superoxide dismutase (76.42% and 81.09%; P < 0.01), catalase (73.33% and 76.47%; P < 0.01), and reactive oxygen species generation (44.04% and 56.14%; P < 0.01) after 24 and 48 hours of exposure, respectively.Statistically significant (P < 0.01) induction of DNA damage was observed by the comet assay in cells exposed to arsenic trioxide.The results demonstrate that arsenic trioxide induces apoptosis and genotoxicity in human hepatocellular carcinoma cells through reactive oxygen species and oxidative stress.

View Article: PubMed Central - PubMed

Affiliation: Cell and Molecular Laboratory, Department of Zoology, Faculty of Science, King Saud University, Riyadh, Saudi Arabia;

ABSTRACT

Background: Arsenic is a ubiquitous environmental toxicant, and abnormalities of the skin, lung, kidney, and liver are the most common outcomes of long-term arsenic exposure. This study was designed to investigate the possible mechanisms of genotoxicity induced by arsenic trioxide in human hepatocellular carcinoma cells.

Methods and results: A mild cytotoxic response of arsenic trioxide was observed in human hepatocellular carcinoma cells, as evident by (3-(4,5-dimethyl thiazol-2-yl)-2, 5-diphenyl tetrazolium bromide) and lactate dehydrogenase assays after 24 and 48 hours of exposure. Arsenic trioxide elicited a significant (P < 0.01) reduction in glutathione (15.67% and 26.52%), with a concomitant increase in malondialdehyde level (67.80% and 72.25%; P < 0.01), superoxide dismutase (76.42% and 81.09%; P < 0.01), catalase (73.33% and 76.47%; P < 0.01), and reactive oxygen species generation (44.04% and 56.14%; P < 0.01) after 24 and 48 hours of exposure, respectively. Statistically significant (P < 0.01) induction of DNA damage was observed by the comet assay in cells exposed to arsenic trioxide. It was also observed that apoptosis occurred through activation of caspase-3 and phosphatidylserine externalization in human hepatocellular carcinoma cells exposed to arsenic trioxide.

Conclusion: The results demonstrate that arsenic trioxide induces apoptosis and genotoxicity in human hepatocellular carcinoma cells through reactive oxygen species and oxidative stress.

No MeSH data available.


Related in: MedlinePlus

Increase in chromosome condensation and caspase-3 activity in human hepatocellular carcinoma cells after exposure to arsenic trioxide for 24 and 48 hours. (A) Control cells, (B) cells exposed to 2.5 μg/mL of arsenic trioxide, and (C) caspase-3 activity.Notes: Each value represents the mean ± standard error of three experiments. *P < 0.01 versus control.Abbreviation: AU, arbitrary units.
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f5-ott-6-075: Increase in chromosome condensation and caspase-3 activity in human hepatocellular carcinoma cells after exposure to arsenic trioxide for 24 and 48 hours. (A) Control cells, (B) cells exposed to 2.5 μg/mL of arsenic trioxide, and (C) caspase-3 activity.Notes: Each value represents the mean ± standard error of three experiments. *P < 0.01 versus control.Abbreviation: AU, arbitrary units.

Mentions: Caspase-3, which plays a key role in the apoptotic pathway, was induced following treatment with arsenic trioxide (Figure 5C). When cells were treated with 0.1, 0.5, 1.5, and 2.5 μg/mL concentrations of arsenic trioxide for 24 and 48 hours, the activity of caspase-3 was increased even from the lowest concentration of 0.1 μg/mL to the highest concentration of 2.5 μg/mL. In addition to caspase-3 activity, chromatin condensation was also evaluated by DAPI staining. When cells were treated with the above concentrations of arsenic trioxide for 24 hours, chromatin condensations were observed in the treated group in a concentration-dependent manner (Figure 5A and B). The caspase-3 activation and chromatin condensation in hepatocellular carcinoma cells suggest that arsenic trioxide caused cell death via an apoptotic process.


Arsenic trioxide-mediated oxidative stress and genotoxicity in human hepatocellular carcinoma cells.

Alarifi S, Ali D, Alkahtani S, Siddiqui MA, Ali BA - Onco Targets Ther (2013)

Increase in chromosome condensation and caspase-3 activity in human hepatocellular carcinoma cells after exposure to arsenic trioxide for 24 and 48 hours. (A) Control cells, (B) cells exposed to 2.5 μg/mL of arsenic trioxide, and (C) caspase-3 activity.Notes: Each value represents the mean ± standard error of three experiments. *P < 0.01 versus control.Abbreviation: AU, arbitrary units.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3569381&req=5

f5-ott-6-075: Increase in chromosome condensation and caspase-3 activity in human hepatocellular carcinoma cells after exposure to arsenic trioxide for 24 and 48 hours. (A) Control cells, (B) cells exposed to 2.5 μg/mL of arsenic trioxide, and (C) caspase-3 activity.Notes: Each value represents the mean ± standard error of three experiments. *P < 0.01 versus control.Abbreviation: AU, arbitrary units.
Mentions: Caspase-3, which plays a key role in the apoptotic pathway, was induced following treatment with arsenic trioxide (Figure 5C). When cells were treated with 0.1, 0.5, 1.5, and 2.5 μg/mL concentrations of arsenic trioxide for 24 and 48 hours, the activity of caspase-3 was increased even from the lowest concentration of 0.1 μg/mL to the highest concentration of 2.5 μg/mL. In addition to caspase-3 activity, chromatin condensation was also evaluated by DAPI staining. When cells were treated with the above concentrations of arsenic trioxide for 24 hours, chromatin condensations were observed in the treated group in a concentration-dependent manner (Figure 5A and B). The caspase-3 activation and chromatin condensation in hepatocellular carcinoma cells suggest that arsenic trioxide caused cell death via an apoptotic process.

Bottom Line: Arsenic trioxide elicited a significant (P < 0.01) reduction in glutathione (15.67% and 26.52%), with a concomitant increase in malondialdehyde level (67.80% and 72.25%; P < 0.01), superoxide dismutase (76.42% and 81.09%; P < 0.01), catalase (73.33% and 76.47%; P < 0.01), and reactive oxygen species generation (44.04% and 56.14%; P < 0.01) after 24 and 48 hours of exposure, respectively.Statistically significant (P < 0.01) induction of DNA damage was observed by the comet assay in cells exposed to arsenic trioxide.The results demonstrate that arsenic trioxide induces apoptosis and genotoxicity in human hepatocellular carcinoma cells through reactive oxygen species and oxidative stress.

View Article: PubMed Central - PubMed

Affiliation: Cell and Molecular Laboratory, Department of Zoology, Faculty of Science, King Saud University, Riyadh, Saudi Arabia;

ABSTRACT

Background: Arsenic is a ubiquitous environmental toxicant, and abnormalities of the skin, lung, kidney, and liver are the most common outcomes of long-term arsenic exposure. This study was designed to investigate the possible mechanisms of genotoxicity induced by arsenic trioxide in human hepatocellular carcinoma cells.

Methods and results: A mild cytotoxic response of arsenic trioxide was observed in human hepatocellular carcinoma cells, as evident by (3-(4,5-dimethyl thiazol-2-yl)-2, 5-diphenyl tetrazolium bromide) and lactate dehydrogenase assays after 24 and 48 hours of exposure. Arsenic trioxide elicited a significant (P < 0.01) reduction in glutathione (15.67% and 26.52%), with a concomitant increase in malondialdehyde level (67.80% and 72.25%; P < 0.01), superoxide dismutase (76.42% and 81.09%; P < 0.01), catalase (73.33% and 76.47%; P < 0.01), and reactive oxygen species generation (44.04% and 56.14%; P < 0.01) after 24 and 48 hours of exposure, respectively. Statistically significant (P < 0.01) induction of DNA damage was observed by the comet assay in cells exposed to arsenic trioxide. It was also observed that apoptosis occurred through activation of caspase-3 and phosphatidylserine externalization in human hepatocellular carcinoma cells exposed to arsenic trioxide.

Conclusion: The results demonstrate that arsenic trioxide induces apoptosis and genotoxicity in human hepatocellular carcinoma cells through reactive oxygen species and oxidative stress.

No MeSH data available.


Related in: MedlinePlus