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Published on: January 7, 2013
[Arsenic trioxide induced cell apoptosis by mitochondria dependent pathway in KB and KBv200 cells]
Yan-Fang Li1, Xu-Dong Wang, Yong-Ju Liang
1Cancer Center,Sun Yat-Sen University, Guangzhou, Guangdong, PR China.
Background & Objective:
Arsenic trioxide (As2O3) is a new drug used to treat the patients with solid tumor,but the mechanism is still unclear. This study was designed to investigate the effect of mitochondrial dependent pathway in apoptosis induced by arsenic trioxide in multidrug resistant KBv200 cells and their parental sensitive KB cells.
Methods:
The cytotoxic effect of As2O3 on KB and KBv200 cells was measured by MTT assay. KB and KBv200 cells were treated respectively with As2O3 for 12, 24, 48 hours. Cell apoptosis was determined by Annexin V FITC staining. Mitochondrial membrane potential was labeled by DiOC6 and examined by flow cytometry.
Results:
Arsenic trioxide showed the inhibition of KB and KBv200 cells proliferation in vitro. The IC(50)s of As2O3 to KB and KBv200 cells were (0.22+/-0.02)microg/ml and (0.20+/-0.01)microg/ml, respectively. As2O3 induced cell apoptosis in time- dependent manner. The apoptosis rates were 20.2%+/-3.1% and 52.2%+/-11.0% for KB cells and 15.8%+/-1.3% and 36.4%+/-5.9% for KBv200 cells under 2.5 microg/ml As2O3 treating 24 h and 48 h, respectively. The levels of mitochondrial membrane potential were concentration-dependently decreased after treating with arsenic trioxide for 12, 24, and 48 hours.
Conclusion:
The decrease of mitochondrial membrane potential maybe plays an important role in apoptosis induced by As2O3.
Insights
Arsenic trioxide (As2O3) induces apoptosis in multidrug-resistant and sensitive cancer cells. This study reveals that As2O3 decreases mitochondrial membrane potential, suggesting its role in cancer cell death.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- Arsenic trioxide (As2O3) is an emerging therapeutic agent for solid tumors.
- The precise mechanism of As2O3-induced apoptosis remains incompletely understood.
- Investigating As2O3's effect on the mitochondrial pathway is crucial for understanding its efficacy.
Purpose of the Study:
- To elucidate the role of the mitochondrial-dependent pathway in As2O3-induced apoptosis.
- To compare the effects of As2O3 on multidrug-resistant KBv200 cells and their parental KB cells.
- To investigate the impact of As2O3 on mitochondrial membrane potential in cancer cells.
Main Methods:
- Cytotoxicity assessed using MTT assay.
- Apoptosis evaluated via Annexin V FITC staining.
- Mitochondrial membrane potential measured using DiOC6 and flow cytometry.
Main Results:
- As2O3 demonstrated significant inhibition of proliferation in both KB and KBv200 cells.
- As2O3 induced apoptosis in a time-dependent manner in both cell lines.
- A concentration-dependent decrease in mitochondrial membrane potential was observed following As2O3 treatment.
Conclusions:
- The reduction in mitochondrial membrane potential is implicated in As2O3-mediated apoptosis.
- As2O3 effectively targets both sensitive and multidrug-resistant cancer cells.
- The mitochondrial pathway is a key mechanism in As2O3's anti-cancer effects.
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