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Differences in susceptibility of HT-29 and A549 cells to statin-induced toxicity: An investigation using high content
Guilin Wei1, Lijuan Xue1, Yadi Zhu1
1Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Abstract:
Statins are a group of hydroxymethylglutaryl coenzyme A reductase inhibitors that are used in the treatment of cardiovascular diseases. However, statins have been found to be cytotoxic, and many unexpected side effects have been reported in clinical applications. The susceptibilities of different cell lines toward statins are diverse, and the mechanisms of cytotoxicity remain unknown. Therefore, the present study aimed to investigate differences in the susceptibility to and mechanisms of statin-induced cytotoxicity in two cell lines, HT-29 and A549, using a high content screening-based multiparametric toxicity assay panel. We found that the two cell types exhibited differing susceptibilities to the cytotoxic effects of the different statins. Additionally, the cytotoxicity was inconsistent between different statins in the two cell lines. Four statins with strong cytotoxicity decreased the viability of HT-29 cells via the mitochondrial pathway, as evidenced by decreased mitochondrial membrane potential, and elevated mitochondrial mass, calcium release and cell apoptosis, and reactive oxygen species. In contrast, these four statins only induced a decrease in the mitochondrial membrane potential in A549 cells. The above results provide an objective reason for future evaluations of cytotoxic differences in cell types and the underlying mechanisms of cytotoxicity in different statins, and provide a good scientific basis for further research on countermeasures against statin-induced cell injuries.
Insights
Statins exhibit varied cytotoxicity across different cell types, impacting cellular viability through distinct mechanisms. This study reveals cell-specific mitochondrial pathway involvement in statin-induced cell injury, crucial for understanding side effects.
Area of Science:
- Pharmacology
- Toxicology
- Cell Biology
Background:
- Statins, HMG-CoA reductase inhibitors, are widely used for cardiovascular disease treatment.
- Clinical use of statins is associated with reported cytotoxic effects and diverse side effects.
- Cellular susceptibility and mechanisms underlying statin-induced cytotoxicity are not fully understood.
Purpose of the Study:
- To investigate differential susceptibility to statin-induced cytotoxicity in HT-29 and A549 cell lines.
- To elucidate the mechanisms of statin-induced cytotoxicity using a multiparametric toxicity assay panel.
- To compare the cytotoxic effects of various statins across different cell types.
Main Methods:
- Utilized a high-content screening-based multiparametric toxicity assay panel.
- Assessed cytotoxicity in HT-29 and A549 cell lines exposed to different statins.
- Evaluated mitochondrial membrane potential, mitochondrial mass, calcium release, apoptosis, and reactive oxygen species.
Main Results:
- HT-29 and A549 cells displayed differential susceptibility to statin-induced cytotoxicity.
- Cytotoxicity varied inconsistently between different statins and cell lines.
- Four potent statins induced HT-29 cell death via mitochondrial pathways (decreased membrane potential, increased mass, calcium release, apoptosis, ROS).
- These statins only decreased mitochondrial membrane potential in A549 cells.
Conclusions:
- Cell type significantly influences susceptibility to statin-induced cytotoxicity.
- Mechanisms of statin cytotoxicity differ between cell lines, with mitochondrial pathways implicated in HT-29 cells.
- Findings provide a basis for further research into statin-induced cell injury and potential countermeasures.
