Anandamide-induced apoptosis in Chang liver cells involves ceramide and JNK/AP-1 pathway

  • Authors:
    • Michela Giuliano
    • Giuseppe Calvaruso
    • Ornella Pellerito
    • Patrizia Portanova
    • Daniela Carlisi
    • Renza Vento
    • Giovanni Tesoriere
  • View Affiliations

  • Published online on: May 1, 2006     https://doi.org/10.3892/ijmm.17.5.811
  • Pages: 811-819
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

In the present study we demonstrate that anandamide, the most important endogenous cannabinoid, markedly induced apoptosis in Chang liver cells, an immortalized non- tumor cell line derived from normal liver tissue, while it induced only modest effects in a number of hepatoma cell lines. The apoptotic effect was reduced by methyl-β-cyclodextrin, a membrane cholesterol depletor, suggesting an interaction between anandamide and the membrane microdomains named lipid rafts. Anandamide effects were mediated by the production of ceramide, as demonstrated by experiments performed with the sphingomyelinase inhibitor, desipramine, or with the sphingomyelinase activator, melittin. This conclusion was confirmed by the observation that exogenous C2-ceramide induced a remarkable apoptotic effect in the same cells. Anandamide-induced apoptosis in Chang liver cells involved oxidative stress and activation of p38/JNK pathway, which was accompanied by a remarkable increase in AP-1 DNA-binding activity. Moreover, the levels of both c-Jun and JunB, two components of the AP-1 complex, and those of FasL and Bim, two transcriptional targets of AP-1, also increased during anandamide treatment. In addition, anandamide increased the level of Bax and caused degradation of full-length Bid with the production of the active truncated form. These effects were accompanied by dissipation of mitochondrial transmembrane potential with the consequent activation of both caspase-3 and caspase-6. On the contrary, in hepatoma cells, anandamide did not induce apoptotic effects and it was not possible to observe any increase in p38/JNK pathway and AP-1 activity after drug treatment. Our results suggest that the induction of cell death in non-tumor Chang liver cells by anandamide was mediated by ceramide, JNK and AP-1 and was dependent on the activation of both the extrinsic and intrinsic pathways of apoptosis.

Related Articles

Journal Cover

May 2006
Volume 17 Issue 5

Print ISSN: 1107-3756
Online ISSN:1791-244X

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Giuliano M, Calvaruso G, Pellerito O, Portanova P, Carlisi D, Vento R and Tesoriere G: Anandamide-induced apoptosis in Chang liver cells involves ceramide and JNK/AP-1 pathway. Int J Mol Med 17: 811-819, 2006.
APA
Giuliano, M., Calvaruso, G., Pellerito, O., Portanova, P., Carlisi, D., Vento, R., & Tesoriere, G. (2006). Anandamide-induced apoptosis in Chang liver cells involves ceramide and JNK/AP-1 pathway. International Journal of Molecular Medicine, 17, 811-819. https://doi.org/10.3892/ijmm.17.5.811
MLA
Giuliano, M., Calvaruso, G., Pellerito, O., Portanova, P., Carlisi, D., Vento, R., Tesoriere, G."Anandamide-induced apoptosis in Chang liver cells involves ceramide and JNK/AP-1 pathway". International Journal of Molecular Medicine 17.5 (2006): 811-819.
Chicago
Giuliano, M., Calvaruso, G., Pellerito, O., Portanova, P., Carlisi, D., Vento, R., Tesoriere, G."Anandamide-induced apoptosis in Chang liver cells involves ceramide and JNK/AP-1 pathway". International Journal of Molecular Medicine 17, no. 5 (2006): 811-819. https://doi.org/10.3892/ijmm.17.5.811