The CB1/VR1 agonist arvanil induces apoptosis through an FADD/caspase-8-dependent pathway

Rocío Sancho, Laureano de la Vega, Giovanni Appendino, Vincenzo Di Marzo, Antonio Macho, Eduardo Muñoz (Lead / Corresponding author)

    Research output: Contribution to journalArticlepeer-review

    22 Citations (Scopus)

    Abstract

    1. Arvanil (N-arachidonoylvanillamine), a nonpungent capsaicin-anandamide hybrid molecule, has been shown to exert biological activities through VR1/CB1-dependent and -independent pathways. We have found that arvanil induces dose-dependent apoptosis in the lymphoid Jurkat T-cell line, but not in peripheral blood T lymphocytes. Apoptosis was assessed by DNA fragmentation through cell cycle and TUNEL analyses. 2. Arvanil-induced apoptosis was initiated independently of any specific phase of the cell cycle, and it was inhibited by specific caspase-8 and -3 inhibitors and by the activation of protein kinase C. In addition, kinetic analysis by Western blots and fluorimetry showed that arvanil rapidly activates caspase-8, -7 and -3, and induces PARP cleavage. 3. The arvanil-mediated apoptotic response was greatly inhibited in the Jurkat-FADDDN cell line, which constitutively expresses a negative dominant form of the adapter molecule Fas-associated death domain (FADD). This cell line does not undergo apoptosis in response to Fas (CD95) stimulation. 4. Using a cytofluorimetric approach, we have found that arvanil induced the production of reactive oxygen species (ROS) in both Jurkat-FADD+ and Jurkat-FADDDN cell lines. However, ROS accumulation only plays a residual role in arvanil-induced apoptosis. 5. These results demonstrate that arvanil-induced apoptosis is essentially mediated through a mechanism that is typical of type II cells, and implicates the death-inducing signalling complex and the activation of caspase-8. This arvanil-apoptotic activity is TRPV1 and CB-independent, and can be of importance for the development of potential anti-inflammatory and antitumoral drugs.

    Original languageEnglish
    Pages (from-to)1035-1044
    Number of pages10
    JournalBritish Journal of Pharmacology
    Volume140
    Issue number6
    DOIs
    Publication statusPublished - Nov 2003

    Keywords

    • Adaptor proteins, Signal transducing
    • Apoptosis
    • Capsaicin
    • Carrier proteins
    • Caspase 8
    • Caspase inhibitors
    • Caspases
    • Cells, Cultured
    • Cysteine proteinase inhibitors
    • DNA fragmentation
    • Dose-response relationship, Drug
    • Fas ligand protein
    • Fas-associated death domain protein
    • Humans
    • In situ Nick-end labeling
    • Jurkat cells
    • Membrane glycoproteins
    • Models, Biological
    • Reactive oxygen snabinoid, CB1pecies
    • Receptor, Cannabinoid, CB1
    • Receptors, Drug
    • Signal transduction
    • T-lymphocytes
    • Time factors
    • Transcription, Genetic

    Fingerprint Dive into the research topics of 'The CB1/VR1 agonist arvanil induces apoptosis through an FADD/caspase-8-dependent pathway'. Together they form a unique fingerprint.

    Cite this