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.

Acta Pharmacologica Sinica
|February 17, 2007
PubMed
Abstract

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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