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...

Abstract Glioblastoma multiforme (GBM) is highly resistant to current anticancer treatments, which makes it crucial to find new therapeutic strategies aimed at improving the poor prognosis of patients suffering from this disease. Δ(9)-Tetrahydrocannabinol (THC), the major active ingredient of marijuana, and other cannabinoid receptor agonists inhibit tumor growth in animal models of cancer, including glioma, an effect that relies, at least in part, on the stimulation of autophagy-mediated apoptosis in tumor cells. Here, we show that the combined administration of THC and temozolomide (TMZ; the benchmark agent for the management of GBM) exerts a strong antitumoral action in glioma xenografts, an effect that is...

We evaluated the ability of cannabidiol (CBD) to impair the migration of tumor cells stimulated by conditioned medium. CBD caused concentration-dependent inhibition of the migration of U87 glioma cells, quantified in a Boyden chamber. Since these cells express both cannabinoid CB1 and CB2 receptors in the membrane, we also evaluated their engagement in the antimigratory effect of CBD. The inhibition of cell was not antagonized either by the selective cannabinoid receptor antagonists SR141716 (CB1) and SR144528 (CB2) or by pretreatment with pertussis toxin, indicating no involvement of classical cannabinoid receptors and/or receptors coupled to Gi/o proteins. These results reinforce the evidence of antitumoral properties...

The pharmacological importance of cannabinoids has been in study for several years. Cannabinoids comprise of (a) the active compounds of the Cannabis sativa plant, (b) endogenous as well as (c) synthetic cannabinoids. Though cannabinoids are clinically used for anti-palliative effects, recent studies open a promising possibility as anti-cancer agents. They have been shown to possess anti-proliferative and anti-angiogenic effects in vitro as well as in vivo in different cancer models. Cannabinoids regulate key cell signaling pathways that are involved in cell survival, invasion, angiogenesis, metastasis, etc. There is more focus on CB1 and CB2, the two cannabinoid receptors which are activated by most of...

Abstract Background: The active components of Cannabis sativa L., Cannabinoids, traditionally used in the field of cancer for alleviation of pain, nausea, wasting and improvement of well-being have received renewed interest in recent years due to their diverse pharmacologic activities such as cell growth inhibition, anti-inflammatory activity and induction of tumor regression. Here we used several experimental approaches, which identified delta-9-tetrahydrocannabinol (Delta(9)-THC) as an essential mediator of cannabinoid antitumoral action. Methods and results: Administration of Delta(9)-THC to glioblastoma multiforme (GBM) cell lines results in a significant decrease in cell viability. Cell cycle analysis showed G(0/1) arrest and did not reveal occurrence of apoptosis in the absence...

Abstract Glioblastoma (GBM) is the most common form of primary adult brain tumors. A majority of GBMs grow invasively into distant brain tissue, leading to tumor recurrence, which is ultimately incurable. It is, therefore, essential to discover master regulators that control GBM invasiveness and target them therapeutically. We demonstrate here that the transcriptional regulator Id-1 plays a critical role in modulating the invasiveness of GBM cell lines and primary GBM cells. Id-1 expression levels positively correlate with glioma cell invasiveness in culture and with histopathological grades in patient biopsies. Id-1 knockdown dramatically reduces GBM cell invasion that is accompanied by profound morphological changes and...