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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

DNA damage in human hepatocellular carcinoma cells after 24 and 48 hours of exposure to different concentrations of arsenic trioxide. (A) Percent tail DNA, (B) olive tail moment (arbitrary unit), (C) control cells, (D) and exposed cells.Notes: Each value represents the mean ± standard error of three experiments performed in duplicate. *P < 0.01 versus control.Abbreviation: EMS, Ethyl methane sulfonate.
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f7-ott-6-075: DNA damage in human hepatocellular carcinoma cells after 24 and 48 hours of exposure to different concentrations of arsenic trioxide. (A) Percent tail DNA, (B) olive tail moment (arbitrary unit), (C) control cells, (D) and exposed cells.Notes: Each value represents the mean ± standard error of three experiments performed in duplicate. *P < 0.01 versus control.Abbreviation: EMS, Ethyl methane sulfonate.

Mentions: DNA damage was measured as percent tail DNA and olive tail moment in both the controls and exposed cells. During electrophoresis, DNA in the cells was observed to migrate more rapidly towards the anode at the highest concentration than at the lowest concentration. The cells exposed to different concentrations of arsenic trioxide showed significantly (P > 0.01) more DNA damage in cells than did the control cells. The gradual nonlinear increase in DNA damage was observed in cells as the dose and duration of exposure to arsenic trioxide increased. The greatest DNA damage was recorded in hepatocellular carcinoma cells exposed to 2.5 μg/mL arsenic trioxide (see Figure 7).


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)

DNA damage in human hepatocellular carcinoma cells after 24 and 48 hours of exposure to different concentrations of arsenic trioxide. (A) Percent tail DNA, (B) olive tail moment (arbitrary unit), (C) control cells, (D) and exposed cells.Notes: Each value represents the mean ± standard error of three experiments performed in duplicate. *P < 0.01 versus control.Abbreviation: EMS, Ethyl methane sulfonate.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3569381&req=5

f7-ott-6-075: DNA damage in human hepatocellular carcinoma cells after 24 and 48 hours of exposure to different concentrations of arsenic trioxide. (A) Percent tail DNA, (B) olive tail moment (arbitrary unit), (C) control cells, (D) and exposed cells.Notes: Each value represents the mean ± standard error of three experiments performed in duplicate. *P < 0.01 versus control.Abbreviation: EMS, Ethyl methane sulfonate.
Mentions: DNA damage was measured as percent tail DNA and olive tail moment in both the controls and exposed cells. During electrophoresis, DNA in the cells was observed to migrate more rapidly towards the anode at the highest concentration than at the lowest concentration. The cells exposed to different concentrations of arsenic trioxide showed significantly (P > 0.01) more DNA damage in cells than did the control cells. The gradual nonlinear increase in DNA damage was observed in cells as the dose and duration of exposure to arsenic trioxide increased. The greatest DNA damage was recorded in hepatocellular carcinoma cells exposed to 2.5 μg/mL arsenic trioxide (see Figure 7).

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