Limits...
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

Phosphatidylserine translocation in human hepatocellular carcinoma cells. (A) Control cells, (B) red fluorescence is propidium iodide indicating disruption of the plasma membrane, and (C) green fluorescence is phosphatidylserine detected on the outer surface of the plasma membrane by Annexin-V-FITC in arsenic trioxide-treated cells.Note: The data are representative of three independent experiments.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3569381&req=5

f6-ott-6-075: Phosphatidylserine translocation in human hepatocellular carcinoma cells. (A) Control cells, (B) red fluorescence is propidium iodide indicating disruption of the plasma membrane, and (C) green fluorescence is phosphatidylserine detected on the outer surface of the plasma membrane by Annexin-V-FITC in arsenic trioxide-treated cells.Note: The data are representative of three independent experiments.

Mentions: Externalization of phosphatidylserine, another marker of apoptosis, is one of the first events in the apoptotic process. The externalization of phosphatidylserine from the inner to the outer surface of the lipid bilayer membrane occurs without disruption of other membrane components. We assessed externalization of phosphatidylserine in hepatocellular carcinoma cells treated with arsenic trioxide using Annexin-V FITC as a specific marker. Both Annexin-V FITC and propidium iodide fluorescence were observed in the arsenic trioxide-treated cells. The results suggest that either early apoptosis or necrosis was induced in the treated cells (Figure 6B and C). No externalization of phosphatidylserine was observed in untreated hepatocellular carcinoma cells (Figure 6A).


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)

Phosphatidylserine translocation in human hepatocellular carcinoma cells. (A) Control cells, (B) red fluorescence is propidium iodide indicating disruption of the plasma membrane, and (C) green fluorescence is phosphatidylserine detected on the outer surface of the plasma membrane by Annexin-V-FITC in arsenic trioxide-treated cells.Note: The data are representative of three independent experiments.
© Copyright Policy
Related In: Results  -  Collection

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

f6-ott-6-075: Phosphatidylserine translocation in human hepatocellular carcinoma cells. (A) Control cells, (B) red fluorescence is propidium iodide indicating disruption of the plasma membrane, and (C) green fluorescence is phosphatidylserine detected on the outer surface of the plasma membrane by Annexin-V-FITC in arsenic trioxide-treated cells.Note: The data are representative of three independent experiments.
Mentions: Externalization of phosphatidylserine, another marker of apoptosis, is one of the first events in the apoptotic process. The externalization of phosphatidylserine from the inner to the outer surface of the lipid bilayer membrane occurs without disruption of other membrane components. We assessed externalization of phosphatidylserine in hepatocellular carcinoma cells treated with arsenic trioxide using Annexin-V FITC as a specific marker. Both Annexin-V FITC and propidium iodide fluorescence were observed in the arsenic trioxide-treated cells. The results suggest that either early apoptosis or necrosis was induced in the treated cells (Figure 6B and C). No externalization of phosphatidylserine was observed in untreated hepatocellular carcinoma cells (Figure 6A).

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