Endogenous and synthetic cannabinoids exert antiproliferative and proapoptotic effects in various types of cancer and in mantle cell lymphoma (MCL). In this study, we evaluated the expression of cannabinoid receptors type 1 and type 2 (CB1 and CB2) in nonHodgkin lymphomas of B cell type (n 5 62). A majority of the lymphomas expressed higher mRNA levels of CB1 and/or CB2 as compared to reactive lymphoid tissue. With the exception of MCL, which uniformly overexpresses both CB1 and CB2, the levels of cannabinoid receptors within other lymphoma entities were highly variable, ranging from 0.1 to 224 times the expression in reactive lymph nodes. Low...

Cannabinoids present an interesting therapeutic potential as antiemetics, appetite stimulants in debilitating diseases (cancer, AIDS and multiple sclerosis), analgesics, and in the treatment of multiple sclerosis and cancer, among other conditions. However, despite their high clinical potential, only few dosage forms are available to date. In this paper, the development of D9 -tetrahydrocannabinol (THC) biodegradable microspheres as an alternative delivery system for cannabinoid parenteral administration is proposed. Tetrahydrocannabinol was encapsulated into biodegradable microspheres by the oil-in-water (o/w) emulsion solvent evaporation method. Several formulations were prepared using different drug:polymer ratios. The influence of antioxidant (a-tocopherol acetate) concentration on the release of THC from the microparticles...

One of the most exciting areas of current research in the cannabinoid field is the study of the potential application of these compounds as antitumoral drugs. Here, we describe the signaling pathway that mediates cannabinoid-induced apoptosis of tumor cells. By using a wide array of experimental approaches, we identify the stress-regulated protein p8 (also designated as candidate of metastasis 1) as an essential mediator of cannabinoid antitumoral action and show that p8 upregulation is dependent on de novo-synthesized ceramide. We also observe that p8 mediates its apoptotic effect via upregulation of the endoplasmic reticulum stress-related genes ATF-4, CHOP, and TRB3. Activation of this pathway...

Recent findings on the inhibition of angiogenesis and vascular endothelial cell proliferation by anthracycline antibiotics, which contain a quinone moiety, make this type of compound a very promising lead in cancer research/therapy. We have reported that a new cannabinoid anticancer quinone, cannabidiol hydroxyquinone (HU-331), is highly effective against tumor xenografts in nude mice. For evaluation of the antiangiogenic action of cannabinoid quinones, collagen-embedded rat aortic ring assay was used. The ability of cannabinoids to cause endothelial cell apoptosis was assayed by TUNEL staining and flow cytometry analysis. To examine the genes and pathways targeted by HU-331 in vascular endothelial cells, human cDNA microarrays and...

Kaposi sarcoma is the most common neoplasm caused by Kaposi sarcoma–associated herpesvirus (KSHV). It is prevalent among the elderly in the Mediterranean, inhabitants of sub-Saharan Africa, and immunocompromised individuals such as organ transplant recipients and AIDS patients. Current treatments for Kaposi sarcoma can inhibit tumor growth but are not able to eliminate KSHV from the host. When the host’s immune system weakens, KSHV begins to replicate again, and active tumor growth ensues. New therapeutic approaches are needed. Cannabidiol (CBD), a plant-derived cannabinoid, exhibits promising antitumor effects without inducing psychoactive side effects. CBD is emerging as a novel therapeutic for various disorders, including cancer. In...

Cannabinoids-endocannaboids are possible preventatives of common diseases including cancers. Cannabinoid receptors (CB1/2, TRPV1) are central components of the system. Many disease-ameliorating effects of cannabinoids-endocannabinoids are receptor mediated, but many are not, indicating nonCBR signaling pathways. Cannabinoids-endocannabinoids are anti-inflammatory, anti-proliferative, anti-invasive, anti-metastatic and pro-apoptotic in most cancers, in vitro and in vivo in animals. They signal through p38, MAPK, JUN, PI3, AKT, ceramide, caspases, MMPs, PPARs, VEGF, NF-jB, p8, CHOP, TRB3 and pro-apoptotic oncogenes (p53,p21 waf1/cip1) to induce cell cycle arrest, autophagy, apoptosis and tumour inhibition. Paradoxically they are pro-proliferative and anti-apoptotic in some cancers. Differences in receptor expression and concentrations of cannabinoids in cancer...

D9 -Tetrahydrocannabinol (THC) is the primary cannabinoid of marijuana and has been shown to either potentiate or inhibit tumor growth, depending on the type of cancer and its pathogenesis. Little is known about the activity of cannabinoids like THC on epidermal growth factor receptor-overexpressing lung cancers, which are often highly aggressive and resistant to chemotherapy. In this study, we characterized the effects of THC on the EGFinduced growth and metastasis of human non-small cell lung cancer using the cell lines A549 and SW-1573 as in vitro models. We found that these cells express the cannabinoid receptors CB1 and CB2, known targets for THC action,...

Mantle cell lymphoma (MCL) is a moderately aggressive B-cell lymphoma that responds poorly to currently used therapeutic protocols. In order to identify tumour characteristics that improve the understanding of biology of MCL, analysis of oligonucleotide microarrays were used to define specific gene expression profiles. Biopsy samples of MCL cases were compared to reactive lymphoid tissue. Among genes differentially expressed in MCL were genes that are involved in the regulation of proliferation, cell signalling, adhesion and homing. Furthermore, some genes with previously unknown function, such as C11orf32, C2orf10, TBC1D9 and ABCA6 were found to be differentially expressed in MCL compared to reactive lymphoid tissue. Of...

In the early stages, prostate cancer is androgendependent; therefore, medical castration has shown significant results during the initial stages of this pathology. Despite this early effect, advanced prostate cancer is resilient to such treatment. Recent evidence shows that derivatives of Cannabis sativa and its analogs may exert a protective effect against different types of oncologic pathologies. The purpose of the present study was to detect the presence of cannabinoid receptors (CB1 and CB2) on cancer cells with a prostatic origin and to evaluate the effect of the in vitro use of synthetic analogs. In order to do this, we used a commercial cell line...

It is well-established that cannabinoids exert palliative effects on some cancer-associated symptoms. In addition evidences obtained during the last fifteen years support that these compounds can reduce tumor growth in animal models of cancer. Cannabinoids have been shown to activate an ER-stress related pathway that leads to the stimulation of autophagy-mediated cancer cell death. In addition, cannabinoids inhibit tumor angiogenesis and decrease cancer cell migration. The mechanisms of resistance to cannabinoid anticancer action as well as the possible strategies to develop cannabinoid-based combinational therapies to fight cancer have also started to be explored. In this review we will summarize these observations (that have already...