Original Article | Published:

Antitumor Pharmacology

Ceramide induces apoptosis in human lung adenocarcinoma A549 cells through mitogen-activated protein kinases

Acta Pharmacologica Sinica volume 28, pages 439445 (2007) | Download Citation

Abstract

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.

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Author information

Affiliations

  1. Department of Surgery, Mini-invasive surgery Center, Teikyo University Mizonokuchi Hospital, Kawasaki 213-8507, Japan

    • Tian-hua Zhang
    • , Nobuo Murata
    •  & Tatsuo Yamakawa
  2. The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China

    • Tian-hua Zhang
    • , Yao Zhang
    •  & Yong-li Li
  3. Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China

    • Jian-feng Liu
  4. Department of Accidents and Emergencies, China-Japan Friendship Hospital, Beijing 100029, China

    • Hai-tao Lu

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DOI

https://doi.org/10.1111/j.1745-7254.2007.00505.x

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