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Se-methylselenocysteine induces apoptosis mediated by reactive oxygen species in HL-60 cells
1Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Yusung-gu, Taejon, Republic of Korea.
Abstract:
Recent studies have implicated apoptosis as one of the most plausible mechanisms of the chemopreventive effects of selenium compounds, and reactive oxygen species (ROS) as important mediators in apoptosis induced by various stimuli. In the present study, we demonstrate that Se-methylselenocysteine (MSC), one of the most effective selenium compounds at chemoprevention, induced apoptosis in HL-60 cells and that ROS plays a crucial role in MSC-induced apoptosis. The uptake of MSC by HL-60 cells occurred quite early, reaching the maximum within 1 h. The dose-dependent decrease in cell viability was observed by MSC treatment and was coincident with increased DNA fragmentation and sub-G(1) population. 50 microM of MSC was able to induce apoptosis in 48% of cell population at a 24 h time point. Moreover, the release of cytochrome c from mitochondria and the activation of caspase-3 and caspase-9 were also observed. The measurement of ROS by dichlorofluorescein fluorescence revealed that dose- and time-dependent increase in ROS was induced by MSC. N-acetylcysteine, glutathione, and deferoxamine blocked cell death, DNA fragmentation, and ROS generation induced by MSC. Moreover, N-acetylcysteine effectively blocked caspase-3 activation and the increase of the sub-G(1) population induced by MSC. These results imply that ROS is a critical mediator of the MSC-induced apoptosis in HL-60 cells.
Insights
Se-methylselenocysteine (MSC), a potent chemopreventive selenium compound, triggers apoptosis in HL-60 cancer cells. Reactive oxygen species (ROS) are critical mediators in this MSC-induced cell death pathway.
Area of Science:
- Biochemistry
- Cell Biology
- Cancer Research
Background:
- Apoptosis is a key mechanism in selenium chemoprevention.
- Reactive oxygen species (ROS) mediate apoptosis induced by various stimuli.
- Se-methylselenocysteine (MSC) is an effective chemopreventive selenium compound.
Purpose of the Study:
- To investigate the role of Se-methylselenocysteine (MSC) in inducing apoptosis in HL-60 cells.
- To determine the involvement of reactive oxygen species (ROS) in MSC-induced apoptosis.
- To elucidate the molecular mechanisms underlying MSC's chemopreventive effects.
Main Methods:
- HL-60 cell culture and treatment with MSC.
- Assessment of cell viability, DNA fragmentation, and sub-G1 population.
- Measurement of ROS generation, cytochrome c release, and caspase activation.
- Inhibition studies using N-acetylcysteine, glutathione, and deferoxamine.
Main Results:
- MSC induced dose- and time-dependent apoptosis in HL-60 cells, evidenced by DNA fragmentation and sub-G1 population.
- MSC treatment led to increased ROS generation, cytochrome c release, and activation of caspase-3 and caspase-9.
- Antioxidants (N-acetylcysteine, glutathione) and deferoxamine significantly blocked MSC-induced cell death, ROS generation, and apoptosis markers.
- N-acetylcysteine inhibited caspase-3 activation and sub-G1 population increase.
Conclusions:
- Se-methylselenocysteine (MSC) effectively induces apoptosis in HL-60 cells.
- Reactive oxygen species (ROS) play a critical role in mediating MSC-induced apoptosis.
- Targeting ROS may be a viable strategy for enhancing the chemopreventive efficacy of selenium compounds.