J Pharmacol Exp Ther. 2009 Nov 4. [Epub ahead of print]
Antitumorigenic Effects of Cannabinoids Beyond Apoptosis.
Freimuth N, Ramer R, Hinz B.
University of Rostock.
According to the World Health Organization the cases of death caused by cancer will have been doubled until the year 2030. By 2010 cancer is expected to be the cause of death number one. It is therefore necessary to explore novel approaches for the treatment of cancer. During past years the antitumorigenic effects of cannabinoids have emerged as an exciting field in cancer research. Apart from their proapoptotic and antiproliferative action, recent research has shown that cannabinoids may likewise affect tumor cell angiogenesis, migration, invasion, adhesion and metastasation. This review will summarize the data concerning the influence of cannabinoids on these locomotive processes beyond modulation of cancer cell apoptosis and proliferation. The findings discussed here provide a new perspective on the antitumorigenic potential of cannabinoids.
PMID: 19889794 [PubMed - as supplied by publisher]
Trends Pharmacol Sci. 2009 Aug;30(8):411-20. Epub 2009 Jul 14.
The Endocannabinoid System of the Skin in Health and Disease: Novel Perspectives and Therapeutic Opportunities.
Bíró T, Tóth BI, Haskó G, Paus R, Pacher P.
Department of Physiology, University of Debrecen, Research Center for Molecular Medicine, Debrecen 4032, Hungary.
The newly discovered endocannabinoid system (ECS; comprising the endogenous lipid mediators endocannabinoids present in virtually all tissues, their G-protein-coupled cannabinoid receptors, biosynthetic pathways and metabolizing enzymes) has been implicated in multiple regulatory functions both in health and disease. Recent studies have intriguingly suggested the existence of a functional ECS in the skin and implicated it in various biological processes (e.g. proliferation, growth, differentiation, apoptosis and cytokine, mediator or hormone production of various cell types of the skin and appendages, such as the hair follicle and sebaceous gland). It seems that the main physiological function of the cutaneous ECS is to constitutively control the proper and well-balanced proliferation, differentiation and survival, as well as immune competence and/or tolerance, of skin cells. The disruption of this delicate balance might facilitate the development of multiple pathological conditions and diseases of the skin (e.g. acne, seborrhea, allergic dermatitis, itch and pain, psoriasis, hair growth disorders, systemic sclerosis and cancer).
PMCID: PMC2757311, PMID: 19608284 [PubMed - indexed for MEDLINE]
J Clin Invest. 2009 May;119(5):1359-72.
Cannabinoid Action Induces Autophagy-Mediated Cell Death Through Stimulation of ER Stress in Human Glioma Cells.
Salazar M, Carracedo A, Salanueva IJ, Hernández-Tiedra S, Lorente M, Egia A, Vázquez P, Blázquez C, Torres S, García S, Nowak J, Fimia GM, Piacentini M, Cecconi F, Pandolfi PP, González-Feria L, Iovanna JL, Guzmán M, Boya P, Velasco G.
Department of Biochemistry and Molecular Biology, Complutense University, Madrid, Spain.
Autophagy can promote cell survival or cell death, but the molecular basis underlying its dual role in cancer remains obscure. Here we demonstrate that delta(9)-tetrahydrocannabinol (THC), the main active component of marijuana, induces human glioma cell death through stimulation of autophagy. Our data indicate that THC induced ceramide accumulation and eukaryotic translation initiation factor 2alpha (eIF2alpha) phosphorylation and thereby activated an ER stress response that promoted autophagy via tribbles homolog 3-dependent (TRB3-dependent) inhibition of the Akt/mammalian target of rapamycin complex 1 (mTORC1) axis. We also showed that autophagy is upstream of apoptosis in cannabinoid-induced human and mouse cancer cell death and that activation of this pathway was necessary for the antitumor action of cannabinoids in vivo. These findings describe a mechanism by which THC can promote the autophagic death of human and mouse cancer cells and provide evidence that cannabinoid administration may be an effective therapeutic strategy for targeting human cancers.
PMCID: PMC2673842, PMID: 19425170 [PubMed - indexed for MEDLINE]