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Acta Pharmacologica Sinica
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Ceramide induces apoptosis in human lung adenocarcinoma A549 cells through mitogen-activated protein kinases
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  • Original Article
  • Published: 01 March 2007

Antitumor Pharmacology

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

  • Tian-hua Zhang1,2,
  • Jian-feng Liu3,
  • Yao Zhang2,
  • Yong-li Li2,
  • Hai-tao Lu4,
  • Nobuo Murata1 &
  • …
  • Tatsuo Yamakawa1 

Acta Pharmacologica Sinica volume 28, pages 439–445 (2007)Cite this article

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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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Authors and 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

Authors
  1. Tian-hua Zhang
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  2. Jian-feng Liu
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Corresponding author

Correspondence to Jian-feng Liu.

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Cite this article

Zhang, Th., Liu, Jf., Zhang, Y. et al. Ceramide induces apoptosis in human lung adenocarcinoma A549 cells through mitogen-activated protein kinases. Acta Pharmacol Sin 28, 439–445 (2007). https://doi.org/10.1111/j.1745-7254.2007.00505.x

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  • Received: 14 August 2006

  • Accepted: 26 September 2006

  • Issue Date: 01 March 2007

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

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Keywords

  • ceramide
  • apoptosis
  • mitogen-activated protein kinases
  • A549 cells

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