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Cannabidiol-induced apoptosis in primary lymphocytes is associated with oxidative stress-dependent activation of caspase-8.
Toxicol Appl Pharmacol. 2008 Feb 01; 226(3):260-70.TA

Abstract

We recently reported that cannabidiol (CBD) exhibited a generalized suppressive effect on T-cell functional activities in splenocytes directly exposed to CBD in vitro or isolated from CBD-administered mice. To investigate the potential mechanisms of CBD effects on T cells, we characterized the pro-apoptotic effect of CBD on primary lymphocytes. The apoptosis of splenocytes was markedly enhanced following CBD exposure in a time- and concentration-dependent manner, as evidenced by nuclear hypodiploidity and DNA strand breaks. Exposure of splenocytes to CBD elicited an early production of reactive oxygen species (ROS) with the peak response at 1 h post CBD treatment. In parallel with the ROS production, a gradual diminishment in the cellular glutathione (GSH) content was detected in CBD-treated splenocytes. Both CBD-mediated ROS production and GSH diminishment were remarkably attenuated by the presence of N-acetyl-L-cysteine (NAC), a thiol antioxidant. In addition, CBD treatment significantly stimulated the activation of caspase-8, which was abrogated in the presence of NAC or GSH. Pretreatment of splenocytes with a cell-permeable inhibitor for caspase-8 significantly attenuated, in a concentration-dependent manner, CBD-mediated apoptosis, but not ROS production. Collectively, the present study demonstrated that the apoptotic effect of CBD in primary lymphocytes is closely associated with oxidative stress-dependent activation of caspase-8.

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Authors+Show Affiliations

Wu HY
Department of Veterinary Medicine, National Taiwan University, No.1, Sec. 4, Roosevelt Road, Taipei, Taiwan 106, ROC.
Chu RM
No affiliation info available
Wang CC
No affiliation info available
Lee CY
No affiliation info available
Lin SH
No affiliation info available
Jan TR
No affiliation info available

MeSH

AcetylcysteineAnimalsApoptosisCannabidiolCaspase 8Caspase InhibitorsCell NucleusCells, CulturedDose-Response Relationship, DrugEnzyme ActivationEnzyme InhibitorsFree Radical ScavengersGlutathioneImmunologic FactorsMaleMiceMice, Inbred BALB COxidative StressReactive Oxygen SpeciesSpleen

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17950393

Citation

Wu, Hsin-Ying, et al. "Cannabidiol-induced Apoptosis in Primary Lymphocytes Is Associated With Oxidative Stress-dependent Activation of Caspase-8." Toxicology and Applied Pharmacology, vol. 226, no. 3, 2008, pp. 260-70.
Wu HY, Chu RM, Wang CC, et al. Cannabidiol-induced apoptosis in primary lymphocytes is associated with oxidative stress-dependent activation of caspase-8. Toxicol Appl Pharmacol. 2008;226(3):260-70.
Wu, H. Y., Chu, R. M., Wang, C. C., Lee, C. Y., Lin, S. H., & Jan, T. R. (2008). Cannabidiol-induced apoptosis in primary lymphocytes is associated with oxidative stress-dependent activation of caspase-8. Toxicology and Applied Pharmacology, 226(3), 260-70.
Wu HY, et al. Cannabidiol-induced Apoptosis in Primary Lymphocytes Is Associated With Oxidative Stress-dependent Activation of Caspase-8. Toxicol Appl Pharmacol. 2008 Feb 1;226(3):260-70. PubMed PMID: 17950393.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cannabidiol-induced apoptosis in primary lymphocytes is associated with oxidative stress-dependent activation of caspase-8. AU - Wu,Hsin-Ying, AU - Chu,Rea-Min, AU - Wang,Chia-Chi, AU - Lee,Chi-Ya, AU - Lin,Shu-Hong, AU - Jan,Tong-Rong, Y1 - 2007/09/20/ PY - 2007/04/19/received PY - 2007/09/12/revised PY - 2007/09/13/accepted PY - 2007/10/24/pubmed PY - 2008/3/19/medline PY - 2007/10/24/entrez SP - 260 EP - 70 JF - Toxicology and applied pharmacology JO - Toxicol Appl Pharmacol VL - 226 IS - 3 N2 - We recently reported that cannabidiol (CBD) exhibited a generalized suppressive effect on T-cell functional activities in splenocytes directly exposed to CBD in vitro or isolated from CBD-administered mice. To investigate the potential mechanisms of CBD effects on T cells, we characterized the pro-apoptotic effect of CBD on primary lymphocytes. The apoptosis of splenocytes was markedly enhanced following CBD exposure in a time- and concentration-dependent manner, as evidenced by nuclear hypodiploidity and DNA strand breaks. Exposure of splenocytes to CBD elicited an early production of reactive oxygen species (ROS) with the peak response at 1 h post CBD treatment. In parallel with the ROS production, a gradual diminishment in the cellular glutathione (GSH) content was detected in CBD-treated splenocytes. Both CBD-mediated ROS production and GSH diminishment were remarkably attenuated by the presence of N-acetyl-L-cysteine (NAC), a thiol antioxidant. In addition, CBD treatment significantly stimulated the activation of caspase-8, which was abrogated in the presence of NAC or GSH. Pretreatment of splenocytes with a cell-permeable inhibitor for caspase-8 significantly attenuated, in a concentration-dependent manner, CBD-mediated apoptosis, but not ROS production. Collectively, the present study demonstrated that the apoptotic effect of CBD in primary lymphocytes is closely associated with oxidative stress-dependent activation of caspase-8. SN - 0041-008X UR - https://www.unboundmedicine.com/medline/citation/17950393/Cannabidiol_induced_apoptosis_in_primary_lymphocytes_is_associated_with_oxidative_stress_dependent_activation_of_caspase_8_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0041-008X(07)00419-X DB - PRIME DP - Unbound Medicine ER -