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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

Cytotoxicity of arsenic trioxide in human hepatocellular carcinoma cells for 24 hours and 48 hours. (A) MTT reduction and (B) lactate dehydrogenase leakage.Notes: Each value represents the mean ± standard error of three experiments performed in duplicate. *P < 0.01 versus control.Abbreviations: LDH lactate dehydrogenase leakage; MTT, 3-(4,5-dimethyl thiazol-2-yl)-2, 5-diphenyl tetrazolium bromide.
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f2-ott-6-075: Cytotoxicity of arsenic trioxide in human hepatocellular carcinoma cells for 24 hours and 48 hours. (A) MTT reduction and (B) lactate dehydrogenase leakage.Notes: Each value represents the mean ± standard error of three experiments performed in duplicate. *P < 0.01 versus control.Abbreviations: LDH lactate dehydrogenase leakage; MTT, 3-(4,5-dimethyl thiazol-2-yl)-2, 5-diphenyl tetrazolium bromide.

Mentions: We examined mitochondrial function (by MTT reduction) and membrane damage (by lactate dehydrogenase leakage) as end points for cytotoxicity. The MTT results demonstrated concentration-dependent and time-dependent cytotoxicity after exposure to arsenic trioxide in the hepatocellular carcinoma cells (Figure 2A). The MTT reduction observed after 24 hours of exposure at the concentrations of 2.5, 5.0, 10, and 20 μg/mL was 86%, 70%, 56.0%, and 40.70%, respectively, with a further reduction to 81%, 53%, 30.41%, and 12.20% after 48 hours of exposure. Arsenic trioxide was also found to induce lactate dehydrogenase leakage in a concentration-dependent and time-dependent manner (Figure 2B).


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)

Cytotoxicity of arsenic trioxide in human hepatocellular carcinoma cells for 24 hours and 48 hours. (A) MTT reduction and (B) lactate dehydrogenase leakage.Notes: Each value represents the mean ± standard error of three experiments performed in duplicate. *P < 0.01 versus control.Abbreviations: LDH lactate dehydrogenase leakage; MTT, 3-(4,5-dimethyl thiazol-2-yl)-2, 5-diphenyl tetrazolium bromide.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3569381&req=5

f2-ott-6-075: Cytotoxicity of arsenic trioxide in human hepatocellular carcinoma cells for 24 hours and 48 hours. (A) MTT reduction and (B) lactate dehydrogenase leakage.Notes: Each value represents the mean ± standard error of three experiments performed in duplicate. *P < 0.01 versus control.Abbreviations: LDH lactate dehydrogenase leakage; MTT, 3-(4,5-dimethyl thiazol-2-yl)-2, 5-diphenyl tetrazolium bromide.
Mentions: We examined mitochondrial function (by MTT reduction) and membrane damage (by lactate dehydrogenase leakage) as end points for cytotoxicity. The MTT results demonstrated concentration-dependent and time-dependent cytotoxicity after exposure to arsenic trioxide in the hepatocellular carcinoma cells (Figure 2A). The MTT reduction observed after 24 hours of exposure at the concentrations of 2.5, 5.0, 10, and 20 μg/mL was 86%, 70%, 56.0%, and 40.70%, respectively, with a further reduction to 81%, 53%, 30.41%, and 12.20% after 48 hours of exposure. Arsenic trioxide was also found to induce lactate dehydrogenase leakage in a concentration-dependent and time-dependent manner (Figure 2B).

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