Se-methylselenocysteine activates caspase-3 in mouse mammary epithelial tumor cells in vitro
1Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Abstract:
Se-methylselenocysteine (MSC) inhibits mouse mammary epithelial tumor cell (TM6) growth. When synchronized TM6 cells were exposed to 50 microM MSC, either for 30 minutes or continuous, the 116 kDa poly(ADP-ribose)polymerase (PARP) was cleaved to an 85 kDa fragment indicative of cells undergoing apoptosis. The earliest cleaved PARP appears at 24 hr time point followed by elevated levels of 85 kDa fragment at 34 hr and 48 hr time points when the cells were exposed to continuous treatment with MSC. Results also showed that MSC increased caspase-3 activity at 24 hr time point. In addition, continuous treatment with MSC induced DNA fragmentation at 34 hr and 48 hr time points with caspase-3 gene expression moderately increased at 16 hr and 24 hr time points. Caspase-6 and -8 were also involved in the MSC-induced apoptosis but to a lesser extent. These results suggest that MSC mediates cleavage of PARP and apoptosis by activating one or more caspases in synchronized TM6 cells and the events are dependent on the duration of treatment.
Insights
Se-methylselenocysteine (MSC) inhibits tumor cell growth by inducing apoptosis. This involves poly(ADP-ribose)polymerase (PARP) cleavage and caspase activation, with effects dependent on treatment duration.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Se-methylselenocysteine (MSC) is a selenium compound with potential anti-cancer properties.
- Understanding the molecular mechanisms of MSC's anti-tumor effects is crucial for therapeutic development.
Purpose of the Study:
- To investigate the effects of Se-methylselenocysteine (MSC) on mouse mammary epithelial tumor cell (TM6) growth.
- To elucidate the molecular pathways, including apoptosis induction, triggered by MSC treatment.
Main Methods:
- Synchronized TM6 cells were treated with 50 microM MSC for varying durations (30 minutes or continuous).
- Poly(ADP-ribose)polymerase (PARP) cleavage, caspase activity (caspase-3), caspase gene expression (caspase-3, -6, -8), and DNA fragmentation were analyzed.
Main Results:
- MSC treatment led to the cleavage of PARP into an 85 kDa fragment, indicating apoptosis.
- Elevated levels of cleaved PARP were observed at 24, 34, and 48 hours of continuous MSC exposure.
- MSC increased caspase-3 activity and gene expression, induced DNA fragmentation, and involved caspases-6 and -8 in apoptosis.
Conclusions:
- Se-methylselenocysteine (MSC) inhibits TM6 tumor cell growth by inducing apoptosis.
- MSC-induced apoptosis is mediated by PARP cleavage and caspase activation, with the extent of these events dependent on treatment duration.
