Tags

Type your tag names separated by a space and hit enter

Cannabidiol-induced apoptosis in human leukemia cells: A novel role of cannabidiol in the regulation of p22phox and Nox4 expression.
Mol Pharmacol. 2006 Sep; 70(3):897-908.MP

Abstract

In the current study, we examined the effects of the nonpsychoactive cannabinoid, cannabidiol, on the induction of apoptosis in leukemia cells. Exposure of leukemia cells to cannabidiol led to cannabinoid receptor 2 (CB2)-mediated reduction in cell viability and induction in apoptosis. Furthermore, cannabidiol treatment led to a significant decrease in tumor burden and an increase in apoptotic tumors in vivo. From a mechanistic standpoint, cannabidiol exposure resulted in activation of caspase-8, caspase-9, and caspase-3, cleavage of poly(ADP-ribose) polymerase, and a decrease in full-length Bid, suggesting possible cross-talk between the intrinsic and extrinsic apoptotic pathways. The role of the mitochondria was further suggested as exposure to cannabidiol led to loss of mitochondrial membrane potential and release of cytochrome c. It is noteworthy that cannabidiol exposure led to an increase in reactive oxygen species (ROS) production as well as an increase in the expression of the NAD(P)H oxidases Nox4 and p22(phox). Furthermore, cannabidiol-induced apoptosis and reactive oxygen species (ROS) levels could be blocked by treatment with the ROS scavengers or the NAD(P)H oxidase inhibitors. Finally, cannabidiol exposure led to a decrease in the levels of p-p38 mitogen-activated protein kinase, which could be blocked by treatment with a CB2-selective antagonist or ROS scavenger. Together, the results from this study reveal that cannabidiol, acting through CB2 and regulation of Nox4 and p22(phox) expression, may be a novel and highly selective treatment for leukemia.

Authors+Show Affiliations

McKallip RJ
Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, 6439 Garner's Ferry Road, Columbia, SC 29209, USA. rmckallip@gw.med.sc.edu
Jia W
No affiliation info available
Schlomer J
No affiliation info available
Warren JW
No affiliation info available
Nagarkatti PS
No affiliation info available
Nagarkatti M
No affiliation info available

MeSH

AnimalsApoptosisCannabidiolCaspasesCell SurvivalCytochromes cEnzyme ActivationExtracellular Signal-Regulated MAP KinasesFemaleHumansJNK Mitogen-Activated Protein KinasesJurkat CellsLeukemiaMembrane PotentialsMiceMitochondrial MembranesNADPH Oxidase 4NADPH OxidasesPhosphorylationReactive Oxygen SpeciesReceptor, Cannabinoid, CB2p38 Mitogen-Activated Protein Kinases

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16754784

Citation

McKallip, Robert J., et al. "Cannabidiol-induced Apoptosis in Human Leukemia Cells: a Novel Role of Cannabidiol in the Regulation of P22phox and Nox4 Expression." Molecular Pharmacology, vol. 70, no. 3, 2006, pp. 897-908.
McKallip RJ, Jia W, Schlomer J, et al. Cannabidiol-induced apoptosis in human leukemia cells: A novel role of cannabidiol in the regulation of p22phox and Nox4 expression. Mol Pharmacol. 2006;70(3):897-908.
McKallip, R. J., Jia, W., Schlomer, J., Warren, J. W., Nagarkatti, P. S., & Nagarkatti, M. (2006). Cannabidiol-induced apoptosis in human leukemia cells: A novel role of cannabidiol in the regulation of p22phox and Nox4 expression. Molecular Pharmacology, 70(3), 897-908.
McKallip RJ, et al. Cannabidiol-induced Apoptosis in Human Leukemia Cells: a Novel Role of Cannabidiol in the Regulation of P22phox and Nox4 Expression. Mol Pharmacol. 2006;70(3):897-908. PubMed PMID: 16754784.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cannabidiol-induced apoptosis in human leukemia cells: A novel role of cannabidiol in the regulation of p22phox and Nox4 expression. AU - McKallip,Robert J, AU - Jia,Wentao, AU - Schlomer,Jerome, AU - Warren,James W, AU - Nagarkatti,Prakash S, AU - Nagarkatti,Mitzi, Y1 - 2006/06/05/ PY - 2006/6/7/pubmed PY - 2006/9/29/medline PY - 2006/6/7/entrez SP - 897 EP - 908 JF - Molecular pharmacology JO - Mol Pharmacol VL - 70 IS - 3 N2 - In the current study, we examined the effects of the nonpsychoactive cannabinoid, cannabidiol, on the induction of apoptosis in leukemia cells. Exposure of leukemia cells to cannabidiol led to cannabinoid receptor 2 (CB2)-mediated reduction in cell viability and induction in apoptosis. Furthermore, cannabidiol treatment led to a significant decrease in tumor burden and an increase in apoptotic tumors in vivo. From a mechanistic standpoint, cannabidiol exposure resulted in activation of caspase-8, caspase-9, and caspase-3, cleavage of poly(ADP-ribose) polymerase, and a decrease in full-length Bid, suggesting possible cross-talk between the intrinsic and extrinsic apoptotic pathways. The role of the mitochondria was further suggested as exposure to cannabidiol led to loss of mitochondrial membrane potential and release of cytochrome c. It is noteworthy that cannabidiol exposure led to an increase in reactive oxygen species (ROS) production as well as an increase in the expression of the NAD(P)H oxidases Nox4 and p22(phox). Furthermore, cannabidiol-induced apoptosis and reactive oxygen species (ROS) levels could be blocked by treatment with the ROS scavengers or the NAD(P)H oxidase inhibitors. Finally, cannabidiol exposure led to a decrease in the levels of p-p38 mitogen-activated protein kinase, which could be blocked by treatment with a CB2-selective antagonist or ROS scavenger. Together, the results from this study reveal that cannabidiol, acting through CB2 and regulation of Nox4 and p22(phox) expression, may be a novel and highly selective treatment for leukemia. SN - 0026-895X UR - https://www.unboundmedicine.com/medline/citation/16754784/Cannabidiol_induced_apoptosis_in_human_leukemia_cells:_A_novel_role_of_cannabidiol_in_the_regulation_of_p22phox_and_Nox4_expression_ DB - PRIME DP - Unbound Medicine ER -