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Saturated Fatty Acids Induce Ceramide-associated Macrophage Cell Death
Published on: October 31, 2017
Ceramide induces apoptosis in human lung adenocarcinoma A549 cells through mitogen-activated protein kinases
Tian-Hua Zhang1, Jian-Feng Liu, Yao Zhang
1Department of Surgery, Mini-invasive surgery Center, Teikyo University Mizonokuchi Hospital, Kawasaki 213-8507, Japan.
Aim:
To provide experimental data for further research on the signal transduction of apoptosis in lung adenocarcinoma cells, we examined the effects of exogenous C2-ceramide administration on several members of the mitogen-activated protein kinase (MAPK) superfamily and caspase-3 in A549 cells.
Methods:
Cell viability and apoptosis were analyzed by cell counting kit-8 assay and flow cytometry. Various MAPK and caspase-3 proteins were detected by Western blotting.
Results:
C2-ceramide selectively altered the phosphorylation state of members of the MAPK superfamily, causing hyperphosphorylation of mitogen-activated protein kinase kinase (MEK)1/2 and the p38 MAPK, but not affecting the phosphorylation of extracellular signal-regulated kinase 1/2 and the c-Jun N-terminal kinase. SB-203580 (a p38 MAPK inhibitor) and p38 siRNA, but not U0126 (a MEK inhibitor), partially rescued cell death induced by C2-ceramide. C2-ceramide promoted the activation of caspase-3.
Conclusion:
Exogenous C2-ceramide induced apoptosis in human lung adenocarcinoma A549 cells. The activation of MAPK and caspase-3 were involved in the mechanisms of C2-ceramide-induced apoptosis in A549 cells.
Insights
Exogenous C2-ceramide induces apoptosis in lung adenocarcinoma A549 cells by activating mitogen-activated protein kinase (MAPK) pathways and caspase-3. This research provides data on apoptosis signal transduction in these cancer cells.
Area of Science:
- Cell Biology
- Molecular Biology
- Cancer Research
Background:
- Lung adenocarcinoma is a major cause of cancer-related mortality.
- Understanding apoptosis pathways is crucial for developing targeted cancer therapies.
- Mitogen-activated protein kinase (MAPK) superfamily and caspase-3 are key regulators of apoptosis.
Purpose of the Study:
- To investigate the effects of C2-ceramide on MAPK signaling and caspase-3 activation in A549 lung adenocarcinoma cells.
- To elucidate the role of MAPK and caspase-3 in C2-ceramide-induced apoptosis.
- To provide experimental data for further research on apoptosis signal transduction.
Main Methods:
- Cell viability and apoptosis were assessed using cell counting kit-8 assay and flow cytometry.
- Western blotting was employed to detect MAPK superfamily members and caspase-3.
- Specific inhibitors (SB-203580, U0126) and small interfering RNA (siRNA) were used to probe MAPK pathway involvement.
Main Results:
- C2-ceramide induced apoptosis in A549 cells.
- C2-ceramide selectively hyperphosphorylated MEK1/2 and p38 MAPK, but not ERK1/2 or JNK.
- Caspase-3 activation was promoted by C2-ceramide, and p38 MAPK inhibition partially rescued cell death.
Conclusions:
- Exogenous C2-ceramide triggers apoptosis in human lung adenocarcinoma A549 cells.
- The observed apoptosis is mediated through the activation of MAPK signaling pathways and caspase-3.
- These findings contribute to understanding the molecular mechanisms of ceramide-induced apoptosis in lung cancer.
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