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Simvastatin induces pyroptosis via ROS/caspase-1/GSDMD pathway in colon cancer
Wei Xie1,2, Mingjing Peng3, Ying Liu4
1Translational medicine centre, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, Hunan, P. R. China.
Background:
The outcome of patients with colon cancer is still unsatisfied nowadays. Simvastatin is a type of statins with anti-cancer activity, but its effect on colon cancer cells remains unclear. The present study is intended to determine the underlying mechanism of simvastatin in treatment of colon cancer.
Methods:
The viability and pyroptosis rate of cells treated and untreated with simvastatin were analysed by CCK-8 and flow cytometry assays, respectively. We used DCFH-DA and flow cytometry to detect reactive oxygen species (ROS) production. Levels of pyroptosis markers were detected by western blotting analysis or immunofluorescence staining. Besides, the anticancer properties of simvastatin on colon cancer were further demonstrated using a cell line based xenograft tumor model.
Results:
Simvastatin treatment in HCT116 and SW620 induced pyroptosis and suppressed cell proliferation, with changes in the expression level of NLPR3, ASC, cleaved-caspase-1, mature IL-1β, IL-18 and GSDMD-N. Moreover, inhibition of caspase-1 and ROS attenuated the effects of simvastatin on cancer cell viability. In addition, it was identified that simvastatin has an anti-tumor effect by down-regulating ROS production and inducing downstream caspase-1 dependent pyroptosis in the subcutaneous transplantation tumors of HCT116 cells in BALB/c nude mice.
Conclusions:
Our in vitro and in vivo results indicated that simvastatin induced pyroptosis through ROS/caspase-1/GSDMD pathway, thereby serving as a potential agent for colon cancer treatment. Video Abstract.
Insights
Simvastatin triggers programmed cell death (pyroptosis) in colon cancer cells by regulating reactive oxygen species (ROS) and the caspase-1 pathway. This finding suggests simvastatin
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Colon cancer outcomes remain unsatisfactory, necessitating novel therapeutic strategies.
- Simvastatin, a statin drug, exhibits potential anti-cancer activity, but its precise mechanism in colon cancer is not fully understood.
- This study investigates the molecular mechanisms underlying simvastatin's effects on colon cancer cells.
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