But patients were warned not to use the drug even though active chemicals halted the spread of the disease.
Cannabis also helped reduce the size of tumours when tested on mice, according to researchers at Spain’s University of Alcala.
But Cancer Research UK’s Dr Lesley Walker said: “This opens a new avenue to explore potential drug targets but it is at a very early stage – it absolutely isn’t the case that men might be able to fight prostate cancer by smoking cannabis.
“Research suggests that prostate cancer cells might stop growing if they are treated with chemicals found in cannabis but more work needs to be done to explore the potential of these cannabinoids in treatment.”
Prostate cancer affects more than 35,000 UK men each year and kills around 10,000.”
“ACTIVE chemicals in cannabis have been shown to halt prostate cancer cell growth according to research published in the British Journal of Cancer.
Researchers from the University of Alcala, in Madrid tested the effects of the active chemicals in cannabis called cannabinoids on three human prostate cancer cell lines – called PC-3, DU-a45 and LNCaP.
The prostate cancer cells carry molecular ‘garages’- called receptors- in which cannabinoids can ‘park’.
The scientists showed for the first time that if cannabinoids ‘park’ on a receptor called CB2, the cancer cells stop multipyling.
Dr Walker added: “This research suggest that prostate cancer cells might stop growing if they are treated with chemicals found in cannabis but more work needs to be done to explore the potential of the cannabinoids in treatment.”
To confirm the findings the scientists switched off the CB2 receptors – or ‘closed the garage doors’- on the prostate cells. When cannabinoids were then added to cells without the CB2 receptor, the prostate cancer cells carried on dividing and growing. This suggests that cannabinoids connect with the CB2 receptors on prostate cancer cells to stop cell division and spread.
Professor Ines Diaz-Laviada, study author at the University of Alcala said: “Our research shows that there are areas on prostate cancer cells which can recognise and talk to chemicals found in cannabis called cannabinoids. These chemicals can stop the division and growth of prostate cancer cells and could become a target for new research into potential drugs to treat prostate cancer.”
Recently, functional cannabinoid receptor-1 (CB1) and vanilloid receptor-1 (TRPV1) have been described in human prostate and prostate cancer-derived cell lines where the activation of the receptors resulted in inhibition of cellular growth. We, however, lack the description of the expression of these molecules in human prostate cancer (PCC) and in benign prostate hyperplasia (BPH).
RESULTS:
CB1 was identified in epithelial and smooth muscle cells types of the human prostate, whereas TRPV1 was exclusively localized to the mucosal cells. We also found that the expression of CB1 and TRPV1 (both at the protein and mRNA levels) were significantly up-regulated in PCC. However, while the increased expression of TRPV1 showed a proper correlation with increasing PCC tumor grades, such phenomenon was not observed with CB1. In addition, we also measured markedly elevated CB1 levels in BPH tissues whilst the expression of TRPV1 was not altered when compared to healthy control prostate.
CONCLUSIONS:
Our findings strongly argue for that (1) the CB1 and TRPV1 molecules as well as their ligands may indeed possess a promising future role in the treatment of PCC; (2) TRPV1 may also serve as a prognostic factor in PCC; and (3) CB1 may act as a potential target molecule in the therapeutic management of BPH.”
“Prostate cancer is the most common malignancy among men of all races and one of the leading causes of cancer death in this population.
The palliative effects of Cannabis sativa (marijuana) and its putative main active ingredient, the Δ9-tetrahydrocannabinol (THC), which include inhibition of nausea and emesis associated with chemo- or radiotherapy, appetite stimulation, pain relief, mood elevation and relief from insomnia in cancer patients, have been well recognized for centuries. In addition to the therapeutic effects outlined above, THC, synthetic cannabinoid ligands and endocannabinoids or endocannabinoid-like substances have all been shown to induce cell death and to inhibit proliferation and/or migration of several murine and/or human cancer cell lines, as well as inhibiting the growth of certain types of tumours or tumour cell xenografts in vivo, including prostate cancer… the results in this paper represent a considerable experimental effort and provide a wealth of important information on how plant-derived, non-psychoactive, cannabinoids can induce apoptosis in prostate carcinoma cells through a variety of mechanisms… The results described in this paper also supplement previous evidence that THC can counteract prostate carcinoma in vitro and in vivo via activation of cannabinoid CB1 and CB2 receptors…” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3570005/
“Because prostate cancer has become the most common cancer diagnosed in men, developing novel targets and mechanism-based agents for its treatment has become a challenging issue. In recent years cannabinoids, the active components of Cannabis sativa Linnaeus (marijuana) and their derivatives have drawn renewed attention because of their diverse pharmacologic activities such as cell growth inhibition, anti-inflammatory effects, and tumor regression . Cannabinoids have been shown to induce apoptosis in gliomas, PC-12 pheochromocytoma, CHP 100 neuroblastoma, and hippocampal neurons in vitro, and most interestingly, regression of C6-cell gliomas in vivo. Further interest in cannabinoid research came from the discovery of specific cannabinoid systems and the cloning of specific cannabinoid receptors. These diversified effects of cannabinoids are now known to be mediated by the activation of specific G protein-coupled receptors that are normally bound by a family of endogenous ligands, the endocannabinoids. Two different cannabinoid receptors have been characterized and cloned from mammalian tissues: the “central” CB1 receptor, and the “peripheral” CB2 receptor.”
“In the present study, we show for the first time that expression levels of both cannabinoid receptors, CB1 and CB2, are higher in human prostate cancer cells than in normal cells. Importantly, we also show that WIN-55,212-2 (CB1/CB2 agonist) treatment with androgen-responsive LNCaP cells results in a dose- and time-dependent inhibition of cell growth with a concomitant induction of apoptosis, decrease in protein and mRNA expression of androgen receptor and prostate-specific antigen (PSA), decrease in secreted PSA levels, protein expression of proliferating cell nuclear antigen (PCNA), and vascular endothelial growth factor (VEGF). We suggest that cannabinoid receptor agonists may be useful in the treatment of human prostate cancer.”
“…non–habit-forming cannabinoid receptor agonists could be developed as novel therapeutic agents for the treatment of prostate cancer.”
“We conclude that cannabinoids should be considered as agents for the management of prostate cancer.”
“Prostate cancer (CaP)2 ranks as the most common noncutaneous malignancy and the second leading cause of cancer-related deaths in American males, with similar trends in many Western countries…The major cause of mortality from this disease is metastasis of hormone refractory cancer cells that fail to respond to hormone ablation therapy. Because surgery and current treatment options have proven to be inadequate in treating and controlling CaP, the search for novel targets and mechanism-based agents for prevention and treatment of this disease has become a priority.”
“In recent years, cannabinoids the active components of Cannabis sativa linnaeus (marijuana) and their derivatives are drawing renewed attention because of their diverse pharmacological activities such as cell growth inhibition, anti-inflammatory effects, and tumor regression. Further interest in cannabinoid research came from the discovery of the cannabinoid system and the cloning of specific cannabinoid receptors. Two cannabinoid receptors have been identified: the “central” CB1 and the “peripheral” CB2 receptor. In a recent study, we have shown that WIN 55,212-2 a mixed CB1/CB2 receptor agonist imparts cell growth inhibitory effects in LNCaP cells via an induction of apoptosis. An important observation of this study was that WIN 55,212-2 treatment did not result in apoptosis of the normal prostate epithelial cell at similar doses.”
“Cannabinoids and their derivatives are drawing considerable attention in the treatment of cancer because of their diverse activities such as cell growth inhibition, anti-inflammatory effects, and tumor regression. Accumulated evidence indicates that cannabinoid receptor(s) could be an important target for the treatment of cancer. We have earlier shown that WIN-55,212-2 induced apoptosis of prostate cancer LNCaP cells is mediated through CB1 and CB2 receptors and suggested that these receptors could be an important targets for the treatment of prostate cancer…”
“Hence, we conclude that cannabinoid receptor agonist should be considered as an effective agent for the treatment of prostate cancer. If our hypothesis is supported by in vivo experiments, the long term implications of our study could be to develop nonhabit-forming cannabinoid agonist (s) for the management of prostate cancer.”
Researchers investigated how delta-9-tetrahydrocannabinol (THC) affects human PC-3 prostate cancer cells, an androgen-refractory cell line derived from a prostate cancer metastasis to bone. THC caused a dramatic, dose-dependent reduction in cell viability and triggered apoptosis, or programmed cell death. The researchers confirmed apoptosis through several independent signs, including changes in the cell membrane, formation of apoptotic bodies, nuclear fragmentation and the characteristic “ladder” pattern of fragmented DNA.
The effect became apparent within two to three days and reached its maximum by six days. THC also produced a dose-dependent increase in apoptotic cells, and the researchers reported that the apoptotic effect was even greater than that produced by ceramide, which they used as a positive control for programmed cell death.
One of the most unusual findings was that THC’s effect did not appear to depend on the conventional cannabinoid-receptor pathway. Although the PC-3 cells expressed CB1 receptors, a potent cannabinoid agonist did not reproduce THC’s effect, a cannabinoid antagonist did not prevent THC-induced cell death, and blocking G-protein signaling with pertussis toxin also failed to stop it. The authors concluded that THC induced apoptosis through a receptor-independent mechanism and suggested that this effect could provide a basis for future investigation of cannabinoids in prostate cancer therapy.
“The effect of delta9-tetrahydrocannabinol (THC), the major psycho-active component of marijuana, in human prostate cancer cells PC-3 was investigated.
THC caused apoptosis in a dose-dependent manner.
Morphological and biochemical changes induced by THC in prostate PC-3 cells shared the characteristics of an apoptotic phenomenon. First, loss of plasma membrane asymmetry determined by fluorescent anexin V binding. Second, presence of apoptotic bodies and nuclear fragmentation observed by DNA staining with 4′,6-diamino-2-phenylindole (DAPI). Third, presence of typical ‘ladder-patterned’ DNA fragmentation. Central cannabinoid receptor expression was observed in PC-3 cells by immunofluorescence studies. However, several results indicated that the apoptotic effect was cannabinoid receptor-independent, such as lack of an effect of the potent cannabinoid agonist WIN 55,212-2, inability of cannabinoid antagonist AM 251 to prevent cellular death caused by THC and absence of an effect of pertussis toxin pre-treatment.”
“Results shown here indicate that the cellular death process induced by THC in prostate tumor cells PC-3 shares the biochemical and morphological changes characteristic of apoptotic cells.”
“Thus, in this study, we have shown that the major active component of marijuana, THC, induced prostate PC-3 cell death by an apoptotic process.
The apoptotic death caused by THC treatment was even higher than that produced by ceramide. In spite of the presence of cannabinoid receptor CB1 in prostate PC-3 cells, THC exerts its action via a non-receptor-mediated pathway. Our results are in concordance with previous studies which demonstrate in other cell types, a cannabinoid induction of apoptosis by a receptor-independent mechanism. Cannabinoids also regulate hematopoietic cell growth independently of receptor. Whatever the precise mechanism underlying the non-receptor-mediated effects of cannabinoids, these molecules regulate fundamental cellular functions like proliferation and cell death.
The apoptotic effect of THC described in this study might provide the basis for future therapeutic application of cannabinoids. Further studies will determinate whether cannabinoids exert other effects in prostate cells.”
“Significant alterations of a balance in the cannabinoid system between the levels of endogenous ligands and their receptors occur during malignant transformation in various types of cancer, including gliomas. Cannabinoids exert anti-proliferative action in tumor cells. Induction of cell death by cannabinoid treatment…”
“Normal tissue toxicity limits the efficacy of current treatment modalities for glioblastoma multiforme (GBM).
We evaluated the influence of cannabinoids on cell proliferation, death, and morphology of human GBM cell lines and in primary human glial cultures, the normal cells from which GBM tumors arise. The influence of a plant derived cannabinoid agonist, Delta(9)-tetrahydrocannabinol Delta(9)-THC), and a potent synthetic cannabinoid agonist, WIN 55,212-2, were compared using time lapse microscopy.
We discovered that Delta(9)-THC decreases cell proliferation and increases cell death of human GBM cells more rapidly than WIN 55,212-2. Delta(9)-THC was also more potent at inhibiting the proliferation of GBM cells compared to WIN 55,212-2. The effects of Delta(9)-THC and WIN 55,212-2 on the GBM cells were partially the result of cannabinoid receptor activation.
The same concentration of Delta(9)-THC that significantly inhibits proliferation and increases death of human GBM cells has no significant impact on human primary glial cultures. Evidence of selective efficacy with WIN 55,212-2 was also observed but the selectivity was less profound, and the synthetic agonist produced a greater disruption of normal cell morphology compared to Delta(9)-THC.”
“Marijuana and its derivatives have been used in medicine for many centuries, and currently there is a renewed interest in the study of the therapeutic effects of cannabinoids…”
“Recently, cannabinoids (CBs) have been shown to possess antitumor properties. Because the psychoactivity of cannabinoid compounds limits their medicinal usage, we undertook the present study to evaluate the in vitro antiproliferative ability of cannabidiol (CBD), a nonpsychoactive cannabinoid compound, on U87 and U373 human glioma cell lines…”
“…the nonpsychoactive CBD was able to produce a significant antitumor activity both in vitro and in vivo, thus suggesting a possible application of CBD as an antineoplastic agent.”
“In conclusion, a cannabinoid-based therapeutic strategy for neural diseases devoid of undesired psychotropic side effects could find in CBD a valuable compound in cancer therapies along with the perspective of evaluating a synergistic effect with other cannabinoid molecules and/or with other chemotherapeutic agents as well as with radiotherapy. Whatever the precise mechanism underlying the CBD effects, the present results suggest a possible application of CBD as a promising, nonpsychoactive, antineoplastic agent.”
