Category Archives: Cancer

Towards the use of non-psychoactive cannabinoids for prostate cancer.

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“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/

Cannabinoid Receptor as a Novel Target for the Treatment of Prostate Cancer

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“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.”

.http://cancerres.aacrjournals.org/content/65/5/1635.long

Cannabinoid Receptor Agonist-induced Apoptosis of Human Prostate Cancer Cells LNCaP Proceeds through Sustained Activation of ERK1/2 Leading to G1 Cell Cycle Arrest

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“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.”

http://www.jbc.org/content/281/51/39480.long

Delta9-tetrahydrocannabinol induces apoptosis in human prostate PC-3 cells via a receptor-independent mechanism.

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Abstract

“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.”

http://www.ncbi.nlm.nih.gov/pubmed/10570948

CYCLOOXYGENASE-2 AND PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR γ CONFER CANNABIDIOL-INDUCED APOPTOSIS OF HUMAN LUNG CANCER CELLS.

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Abstract

“The antitumorigenic mechanism of cannabidiol (CBD) is still controversial. This study investigates the role of cyclooxygenase-2 (COX-2) and peroxisome proliferator activated receptor γ (PPARγ) in CBDs proapoptotic and tumor-regressive action. In lung cancer cell lines (A549, H460) and primary cells from a lung cancer patient CBD elicited decreased viability associated with apoptosis. Apoptotic cell death by CBD was suppressed by NS-398 (COX-2 inhibitor), GW-9662 (PPARγ antagonist) and siRNA targeting COX-2 and PPARγ. CBD-induced apoptosis was paralleled by upregulation of COX-2 and PPARγ mRNA and protein expression with a maximum induction of COX-2 mRNA after 8 h and continuous increases of PPARγ mRNA when compared to vehicle. In response to CBD tumor cell lines exhibited increased levels of COX-2-dependent prostaglandins (PGs) among which PGD2 and 15-deoxy-Δ12,14-PGJ2 (15d-PGJ2) caused a translocation of PPARγ to the nucleus and induced a PPARγ-dependent apoptotic cell death. Moreover, in A549-xenografted nude mice CBD caused upregulation of COX-2 and PPARγ in tumor tissue, and tumor regression that was fully reversible by GW-9662. Together, our data demonstrate a novel proapoptotic mechanism of CBD involving initial upregulation of COX-2 and PPARγ and a subsequent nuclear translocation of PPARγ by COX-2-dependent PGs.”

http://www.ncbi.nlm.nih.gov/pubmed/23220503

Baby Recovered From Brain Tumor With Daily Dose of Marijuana

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“Anyone who has ever known and loved someone using chemotherapy knows just what a toxic cocktail those drugs truly are. So when faced with the idea that an 8-month-old baby could go through those horrific  side effects or try something else, namely marijuana, to treat a brain tumor, my money is on the “something else” every time.”

“This is exactly the question parents of an 8-month-old baby were faced with recently when they opted to treat their baby with cannabinoid oil (a form of marijuana) on the baby’s pacifier twice a day. Within two months the tumor had shrunk so dramatically that the baby’s doctor’s did not have to use chemo. Amazing, no?”

“The long term effects of marijuana on a baby are probably unknown, but the long term effects of chemotherapy may be just as harmful, if not even worse. At least cannabis can be grown safely and organically and given in as natural a state as possible.”

“Ordinarily I would frown on parents giving any kind of substance to a baby, but a baby with a brain tumor is another kind of story. In this case, the cannabis helped. Maybe this is the beginning of less invasive treatment methods with fewer side effects. Wouldn’t that be a miracle for ALL children?”

“Would you give your baby cannabinoid oil?”

Read more: http://thestir.cafemom.com/baby/147477/baby_recovered_from_brain_tumor?fb_action_ids=471912052845441&fb_action_types=og.recommends&fb_ref=post_top&fb_source=aggregation&fb_aggregation_id=288381481237582

Cannabinoid signaling in glioma cells

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“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…”

 http://www.ncbi.nlm.nih.gov/pubmed/22879071

Cannabinoids and gliomas.

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Abstract

“Cannabinoids, the active components of Cannabis sativa L., act in the body by mimicking endogenous substances–the endocannabinoids–that activate specific cell surface receptors. Cannabinoids exert various palliative effects in cancer patients. In addition, cannabinoids inhibit the growth of different types of tumor cells, including glioma cells, in laboratory animals. They do so by modulating key cell signaling pathways, mostly the endoplasmic reticulum stress response, thereby inducing antitumoral actions such as the apoptotic death of tumor cells and the inhibition of tumor angiogenesis. Of interest, cannabinoids seem to be selective antitumoral compounds, as they kill glioma cells, but not their non-transformed astroglial counterparts. On the basis of these preclinical findings, a pilot clinical study of Delta(9)-tetrahydrocannabinol (THC) in patients with recurrent glioblastoma multiforme has been recently run. The good safety profile of THC, together with its possible growth-inhibiting action on tumor cells, justifies the setting up of future trials aimed at evaluating the potential antitumoral activity of cannabinoids.”

http://www.ncbi.nlm.nih.gov/pubmed/17952650

Cannabinoids selectively inhibit proliferation and induce death of cultured human glioblastoma multiforme cells

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Journal of Neuro-Oncology

“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.”

https://www.ncbi.nlm.nih.gov/pubmed/16078104

https://link.springer.com/article/10.1007%2Fs11060-004-5950-2

Delta 9-tetrahydrocannabinol inhibits cell cycle progression by downregulation of E2F1 in human glioblastoma multiforme cells.

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“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.”

“CONCLUSIONS:

Delta(9)-THC is shown to significantly affect viability of GBM cells via a mechanism that appears to elicit G(1) arrest due to downregulation of E2F1 and Cyclin A. Hence, it is suggested that Delta(9)-THC and other cannabinoids be implemented in future clinical evaluation as a therapeutic modality for brain tumors.”

http://www.ncbi.nlm.nih.gov/pubmed/17934890