Conclusions of peer-reviewed medical studies (as r
Post# of 36728
Posted On: 11/09/2013 10:02:45 PM
Conclusions of peer-reviewed medical studies (as reported in scientific journals) examining anti-cancer, anti-tumor effects of cannabinoids (THC, CBDs) in respect to various types of cancers.
Brain cancer
http://www.nature.com/bjc/journal/v95/n2/abs/6603236a.html
Nature
British Journal of Cancer (2006) 95, 197–203. doi:10.1038/sj.bjc.6603236 www.bjcancer.com
Delta9-Tetrahydrocannabinol (THC) and other cannabinoids inhibit tumour growth and angiogenesis in animal models, so their potential application as antitumoral drugs has been suggested. However, the antitumoral effect of cannabinoids has never been tested in humans.
Here we report the first clinical study aimed at assessing cannabinoid antitumoral action, specifically a pilot phase I trial in which nine patients with recurrent glioblastoma multiforme were administered THC intratumoraly. The patients had previously failed standard therapy (surgery and radiotherapy) and had clear evidence of tumour progression.
Cannabinoid delivery was safe and could be achieved without overt psychoactive effects. Median survival of the cohort from the beginning of cannabinoid administration was 24 weeks (95 % confidence interval: 15–33). Delta9 -Tetrahydrocannabinol inhibited tumour-cell proliferation in vitro and decreased tumour-cell Ki67 immunostaining when administered to two patients. The fair safety profile of THC, together with its possible antiproliferative action on tumour cells reported here and in other studies, may set the basis for future trials aimed at evaluating the potential antitumoral activity of cannabinoids.
http://www.jneurosci.org/content/21/17/6475.abstract
The Journal of Neuroscience
Neuroprotection by Delta9-Tetrahydrocannabinol, the Main Active Compound in Marijuana, against Ouabain-Induced In Vivo Excitotoxicity
Excitotoxicity is a paradigm used to explain the biochemical events in both acute neuronal damage and in slowly progressive, neurodegenerative diseases. [...]
These results provide evidence that the cannabinoid system can serve to protect the brain against neurodegeneration.
http://mct.aacrjournals.org/content/10/1/90.abstract
Molecular Cancer Therapeutics
A Combined Preclinical Therapy of Cannabinoids and Temozolomide against Glioma
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. ?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 also observed in tumors that are resistant to TMZ treatment.
Department of Pediatricsy, State University of New York, Upstate Medical University, Syracuse, NY, USA.
Oral cancer
http://www.ncbi.nlm.nih.gov/pubmed/20516734
Pharmacology. 2010;85(6):328-35. doi: 10.1159/000312686. Epub 2010 Jun 2.
Cannabinoids inhibit cellular respiration of human oral cancer cells.
BACKGROUND AND PURPOSE: The primary cannabinoids, Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and Delta(8) -tetrahydrocannabinol (Delta(8) -THC) are known to disturb the mitochondrial function and possess antitumor activities.
CONCLUSIONS AND IMPLICATIONS: These results show the cannabinoids are potent inhibitors of Tu183 cellular respiration and are toxic to this highly malignant tumor.
Breast cancer
http://www.pnas.org/content/95/14/8375.full.pdf+html
Proceedings of the National Academy of Science USA
Vol. 95, pp. 8375– 8380, July 1998
The endogenous cannabinoid anandamide inhibits human breast
cancer cell proliferation
Anandamide was the first brain metabolite shown to act as a ligand of ‘‘central’’ CB1 cannabinoid receptors.
Here we report that the endogenous cannabinoid potently and selectively inhibits the proliferation of human beast cancer cells in vitro.
Lung cancer
http://www.nature.com/onc/journal/v27/n3/abs/1210641a.html
Nature
Oncogene (2008)
27, 339–346; doi:10.1038/sj.onc.1210641; published online 9 July 2007
Delta9-Tetrahydrocannabinol inhibits epithelial growth factor-induced lung cancer cell migration in vitro as well as its growth and metastasis in vivo
Additionally, in in vivo studies in severe combined immunodeficient mice, there was significant inhibition of the subcutaneous tumor growth and lung metastasis of A549 cells in THC-treated animals as compared to vehicle-treated controls. Tumor samples from THC-treated animals revealed antiproliferative and antiangiogenic effects of THC.
Uterine, Testicular, and Pancreatic Cancers
http://cancerres.aacrjournals.org/content/66/...8.abstract
National Cancer Institute
During this 2-year study, groups of mice and rats were given various doses of THC by gavage. A dose-related decrease in the incidence of hepatic adenoma tumors and hepatocellular carcinoma (HCC) was observed in the mice.
Decreased incidences of benign tumors (polyps and adenomas) in other organs (mammary gland, uterus, pituitary, testis, and pancreas) were also noted in the rats. In another study, delta-9-THC, delta-8-THC, and cannabinol were found to inhibit the growth of Lewis lung adenocarcinoma cells in vitro and in vivo .[4] In addition, other tumors have been shown to be sensitive to cannabinoid-induced growth inhibition.[5-8]
Prostate cancer
http://www.ncbi.nlm.nih.gov/pubmed/12746841?dopt=Abstract
Prostate. 2003 Jun 15;56(1):1-12.
Anti-proliferative and apoptotic effects of anandamide in human prostatic cancer cell lines
BACKGROUND: Anandamide (ANA) is an endogenous lipid which acts as a cannabinoid receptor ligand and with potent anticarcinogenic activity in several cancer cell types.
CONCLUSIONS: The potent anti-proliferative and cytotoxic effects of ANA on metastatic prostatic cancer cells might provide basis for the design of new therapeutic agents for effective treatment of recurrent and invasive prostatic cancers.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3...ool=pubmed
Indian Journal of Urology. 2012 Jan-Mar; 28(1): 9–14.
Prostate cancer is ... the second most common cause of cancer death in the United States.[1]
Prostate cancer is the most common cancer in American men except for non-melanoma skin cancer. In the United States, an estimated 217,730 cases will be diagnosed in 2010 and 32,050 deaths will occur.[1] Its frequency has increased in part due to the widespread availability of serum PSA testing.
...the endocannabinoid signaling system has recently been the focus of medical research and considered a potential therapeutic target[15–17] since the late 1980s when Howlett and colleagues[3] identified and characterized the distinct cannabinoid receptor in rat brain.
In 2005, Sarfaraz and colleagues[30] showed increased expression of both CB1 and CB2 receptors in cultured prostate cancer cells when compared with normal prostate cells, treatment of prostate cancer cells with cannabinoid CB1/CB2 agonist WIN-55,212-2 results in a dose and time dependent decrease in cell viability ,and increased apoptosis along with decrease in androgen receptor protein expression, PSA expression, and secreted PSA, suggesting that cannabinoids should be considered as agents for the management of prostate cancer.
http://www.ncbi.nlm.nih.gov/pubmed/22594963
British Journal of Pharmacology. 2013 Jan;168(1):79-102. doi: 10.1111/j.1476-5381.2012.02027.x.
Non-THC cannabinoids inhibit prostate carcinoma growth in vitro and in vivo: pro-apoptotic effects and underlying mechanisms.
KEY RESULTS: Cannabidiol (CBD) significantly inhibited cell viability. ... CBD-BDS (i.p.) potentiated the effects of bicalutamide and docetaxel against LNCaP and DU-145 xenograft tumours and, given alone, reduced LNCaP xenograft size. CBD (1-10 µM) induced apoptosis and induced markers of intrinsic apoptotic pathways (PUMA and CHOP expression and intracellular Ca(2+)).
CONCLUSIONS AND IMPLICATIONS: These data support the clinical testing of CBD against prostate carcinoma.
Colon/rectal cancer
http://www.ncbi.nlm.nih.gov/pubmed/22231745
Journal of Molecular Medicine (Berl). 2012 Aug;90(8) :925-34. doi: 10.1007/s00109-011-0856-x. Epub 2012 Jan 10.
Chemopreventive effect of the non-psychotropic phytocannabinoid cannabidiol on experimental colon cancer.
Colon cancer affects millions of individuals in Western countries. Cannabidiol, a safe and non-psychotropic ingredient of Cannabis sativa, exerts pharmacological actions (antioxidant and intestinal antinflammatory) and mechanisms (inhibition of endocannabinoid enzymatic degradation) potentially beneficial for colon carcinogenesis.
In colorectal carcinoma cell lines, cannabidiol protected DNA from oxidative damage, increased endocannabinoid levels and reduced cell proliferation in a CB(1)-, TRPV1- and PPAR?-antagonists sensitive manner. It is concluded that cannabidiol exerts chemopreventive effect in vivo and reduces cell proliferation through multiple mechanisms.
Cancer of the blood
http://molpharm.aspetjournals.org/content/70/5/1612.abstract
Cannabinoid Receptor-Mediated Apoptosis Induced by R(+)-Methanandamide and Win55,212-2 Is Associated with Ceramide Accumulation and p38 Activation in Mantle Cell Lymphoma
Abstract
We have recently shown that cannabinoids induce growth inhibition and apoptosis in mantle cell lymphoma (MCL), a malignant B-cell lymphoma that expresses high levels of cannabinoid receptor types 1 and 2 (CB1 and CB2). In the current study, the role of each receptor and the signal transduction triggered by receptor ligation were investigated.
Taken together, these results suggest that concurrent ligation of CB1 and CB2 with either R(+)-MA or Win55 induces apoptosis via a sequence of events in MCL cells: accumulation of ceramide, phosphorylation of p38, depolarization of the mitochondrial membrane, and caspase activation. Although induction of apoptosis was observed in both MCL cell lines and primary MCL, normal B cells remained unaffected. The present data suggest that targeting CB1/CB2 may have therapeutic potential for the treatment of mantle cell lymphoma.
http://www.ncbi.nlm.nih.gov/pubmed/12091357
Blood. 2002 Jul 15;100(2):627-34.
Targeting CB2 cannabinoid receptors as a novel therapy to treat malignant lymphoblastic disease.
Together, the current data demonstrate that CB2 cannabinoid receptors expressed on malignancies of the immune system may serve as potential targets for the induction of apoptosis. Also, because CB2 agonists lack psychotropic effects, they may serve as novel anticancer agents to selectively target and kill tumors of immune origin.
http://www.ncbi.nlm.nih.gov/pubmed/12511587
J Clin Invest. 2003 Jan;111(1):43-50.
Inhibition of skin tumor growth and angiogenesis in vivo by activation of cannabinoid receptors.
Nonmelanoma skin cancer is one of the most common malignancies in humans.
Cannabinoid-treated tumors showed an increased number of apoptotic cells. This was accompanied by impairment of tumor vascularization, as determined by altered blood vessel morphology and decreased expression of proangiogenic factors (VEGF, placental growth factor, and angiopoietin 2). Abrogation of EGF-R function was also observed in cannabinoid-treated tumors. These results support a new therapeutic approach for the treatment of skin tumors.
Liver cancer
http://www.ncbi.nlm.nih.gov/pubmed/21475304
Cell Death Differ. 2011 Jul;18(7):1099-111. doi: 10.1038/cdd.2011.32. Epub 2011 Apr 8.
Anti-tumoral action of cannabinoids on hepatocellular carcinoma: role of AMPK-dependent activation of autophagy.
Hepatocellular carcinoma (HCC) (Liver cancer) is the third cause of cancer-related death worldwide. When these tumors are in advanced stages, few therapeutic options are available. Therefore, it is essential to search for new treatments to fight this disease. In this study, we investigated the effects of cannabinoids--a novel family of potential anticancer agents--on the growth of HCC
We found that delta(9)-tetrahydrocannabinol (delta(9)-THC, the main active component of Cannabis sativa) and JWH-015 (a cannabinoid receptor 2 (CB(2)) cannabinoid receptor-selective agonist) reduced the viability of the human HCC cell lines HepG2 (human hepatocellular liver carcinoma cell line) and HuH-7 (hepatocellular carcinoma cells), an effect that relied on the stimulation of CB(2) receptor.
In vivo studies revealed that delta(9)-THC and JWH-015 reduced the growth of HCC subcutaneous xenografts, an effect that was not evident when autophagy was genetically of pharmacologically inhibited in those tumors.
Moreover, cannabinoids were also able to inhibit tumor growth and ascites in an orthotopic model of HCC xenograft. Our findings may contribute to the design of new therapeutic strategies for the management of HCC.
Biliary tract cancer
http://www.ncbi.nlm.nih.gov/pubmed/19916793
Cancer Invest. 2010 May;28(4):357-63. doi: 10.3109/07357900903405934.
The dual effects of delta(9)-tetrahydrocannabinol on cholangiocarcinoma cells: anti-invasion activity at low concentration and apoptosis induction at high concentration.
Currently, only gemcitabine plus platinum demonstrates the considerable activity for cholangiocarcinoma. The anticancer effect of Delta (9)-tetrahydrocannabinol (THC), the principal active component of cannabinoids has been demonstrated in various kinds of cancers. We therefore evaluate the antitumor effects of THC on cholangiocarcinoma cells. Both cholangiocarcinoma cell lines and surgical specimens from cholangiocarcinoma patients expressed cannabinoid receptors.
THC inhibited cell proliferation, migration and invasion, and induced cell apoptosis. THC also decreased actin polymerization and reduced tumor cell survival in anoikis assay. pMEK1/2 and pAkt demonstrated the lower extent than untreated cells.
Consequently, THC is potentially used to retard cholangiocarcinoma cell growth and metastasis.
Cancer general
http://www.ncbi.nlm.nih.gov/pubmed/12514108
FASEB J. 2003 Mar;17(3):529-31. Epub 2003 Jan 2.
Inhibition of tumor angiogenesis by cannabinoids.
Cannabinoids, the active components of marijuana and their derivatives, induce tumor regression in rodents (8) . However, the mechanism of cannabinoid antitumoral action in vivo is as yet unknown. Here we show that local administration of a nonpsychoactive cannabinoid to mice inhibits angiogenesis of malignant gliomas as determined by immunohistochemical analyses and vascular permeability assays. In vitro and in vivo experiments show that at least two mechanisms may be involved in this cannabinoid action: the direct inhibition of vascular endothelial cell migration and survival as well as the decrease of the expression of proangiogenic factors (vascular endothelial growth factor and angiopoietin-2) and matrix metalloproteinase-2 in the tumors. Inhibition of tumor angiogenesis may allow new strategies for the design of cannabinoid-based antitumoral therapies.
http://www.ncbi.nlm.nih.gov/pubmed/15313899
Cancer Res. 2004 Aug 15;64(16):5617-23.
Cannabinoids inhibit the vascular endothelial growth factor pathway in gliomas.
Cannabinoids inhibit tumor angiogenesis in mice, but the mechanism of their antiangiogenic action is still unknown. Because the vascular endothelial growth factor (VEGF) pathway plays a critical role in tumor angiogenesis, here we studied whether cannabinoids affect it. As a first approach, cDNA array analysis showed that cannabinoid administration to mice bearing s.c. gliomas lowered the expression of various VEGF pathway-related genes. The use of other methods (ELISA, Western blotting, and confocal microscopy) provided additional evidence that cannabinoids depressed the VEGF pathway by decreasing the production of VEGF and the activation of VEGF receptor (VEGFR)-2, the most prominent VEGF receptor, in cultured glioma cells and in mouse gliomas. Cannabinoid-induced inhibition of VEGF production and VEGFR-2 activation was abrogated both in vitro and in vivo by pharmacological blockade of ceramide biosynthesis. These changes in the VEGF pathway were paralleled by changes in tumor size. Moreover, intratumoral administration of the cannabinoid Delta9-tetrahydrocannabinol to two patients with glioblastoma multiforme (grade IV astrocytoma) decreased VEGF levels and VEGFR-2 activation in the tumors. Because blockade of the VEGF pathway constitutes one of the most promising antitumoral approaches currently available, the present findings provide a novel pharmacological target for cannabinoid-based therapies.
Brain cancer
http://www.nature.com/bjc/journal/v95/n2/abs/6603236a.html
Nature
British Journal of Cancer (2006) 95, 197–203. doi:10.1038/sj.bjc.6603236 www.bjcancer.com
Delta9-Tetrahydrocannabinol (THC) and other cannabinoids inhibit tumour growth and angiogenesis in animal models, so their potential application as antitumoral drugs has been suggested. However, the antitumoral effect of cannabinoids has never been tested in humans.
Here we report the first clinical study aimed at assessing cannabinoid antitumoral action, specifically a pilot phase I trial in which nine patients with recurrent glioblastoma multiforme were administered THC intratumoraly. The patients had previously failed standard therapy (surgery and radiotherapy) and had clear evidence of tumour progression.
Cannabinoid delivery was safe and could be achieved without overt psychoactive effects. Median survival of the cohort from the beginning of cannabinoid administration was 24 weeks (95 % confidence interval: 15–33). Delta9 -Tetrahydrocannabinol inhibited tumour-cell proliferation in vitro and decreased tumour-cell Ki67 immunostaining when administered to two patients. The fair safety profile of THC, together with its possible antiproliferative action on tumour cells reported here and in other studies, may set the basis for future trials aimed at evaluating the potential antitumoral activity of cannabinoids.
http://www.jneurosci.org/content/21/17/6475.abstract
The Journal of Neuroscience
Neuroprotection by Delta9-Tetrahydrocannabinol, the Main Active Compound in Marijuana, against Ouabain-Induced In Vivo Excitotoxicity
Excitotoxicity is a paradigm used to explain the biochemical events in both acute neuronal damage and in slowly progressive, neurodegenerative diseases. [...]
These results provide evidence that the cannabinoid system can serve to protect the brain against neurodegeneration.
http://mct.aacrjournals.org/content/10/1/90.abstract
Molecular Cancer Therapeutics
A Combined Preclinical Therapy of Cannabinoids and Temozolomide against Glioma
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. ?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 also observed in tumors that are resistant to TMZ treatment.
Department of Pediatricsy, State University of New York, Upstate Medical University, Syracuse, NY, USA.
Oral cancer
http://www.ncbi.nlm.nih.gov/pubmed/20516734
Pharmacology. 2010;85(6):328-35. doi: 10.1159/000312686. Epub 2010 Jun 2.
Cannabinoids inhibit cellular respiration of human oral cancer cells.
BACKGROUND AND PURPOSE: The primary cannabinoids, Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and Delta(8) -tetrahydrocannabinol (Delta(8) -THC) are known to disturb the mitochondrial function and possess antitumor activities.
CONCLUSIONS AND IMPLICATIONS: These results show the cannabinoids are potent inhibitors of Tu183 cellular respiration and are toxic to this highly malignant tumor.
Breast cancer
http://www.pnas.org/content/95/14/8375.full.pdf+html
Proceedings of the National Academy of Science USA
Vol. 95, pp. 8375– 8380, July 1998
The endogenous cannabinoid anandamide inhibits human breast
cancer cell proliferation
Anandamide was the first brain metabolite shown to act as a ligand of ‘‘central’’ CB1 cannabinoid receptors.
Here we report that the endogenous cannabinoid potently and selectively inhibits the proliferation of human beast cancer cells in vitro.
Lung cancer
http://www.nature.com/onc/journal/v27/n3/abs/1210641a.html
Nature
Oncogene (2008)
27, 339–346; doi:10.1038/sj.onc.1210641; published online 9 July 2007
Delta9-Tetrahydrocannabinol inhibits epithelial growth factor-induced lung cancer cell migration in vitro as well as its growth and metastasis in vivo
Additionally, in in vivo studies in severe combined immunodeficient mice, there was significant inhibition of the subcutaneous tumor growth and lung metastasis of A549 cells in THC-treated animals as compared to vehicle-treated controls. Tumor samples from THC-treated animals revealed antiproliferative and antiangiogenic effects of THC.
Uterine, Testicular, and Pancreatic Cancers
http://cancerres.aacrjournals.org/content/66/...8.abstract
National Cancer Institute
During this 2-year study, groups of mice and rats were given various doses of THC by gavage. A dose-related decrease in the incidence of hepatic adenoma tumors and hepatocellular carcinoma (HCC) was observed in the mice.
Decreased incidences of benign tumors (polyps and adenomas) in other organs (mammary gland, uterus, pituitary, testis, and pancreas) were also noted in the rats. In another study, delta-9-THC, delta-8-THC, and cannabinol were found to inhibit the growth of Lewis lung adenocarcinoma cells in vitro and in vivo .[4] In addition, other tumors have been shown to be sensitive to cannabinoid-induced growth inhibition.[5-8]
Prostate cancer
http://www.ncbi.nlm.nih.gov/pubmed/12746841?dopt=Abstract
Prostate. 2003 Jun 15;56(1):1-12.
Anti-proliferative and apoptotic effects of anandamide in human prostatic cancer cell lines
BACKGROUND: Anandamide (ANA) is an endogenous lipid which acts as a cannabinoid receptor ligand and with potent anticarcinogenic activity in several cancer cell types.
CONCLUSIONS: The potent anti-proliferative and cytotoxic effects of ANA on metastatic prostatic cancer cells might provide basis for the design of new therapeutic agents for effective treatment of recurrent and invasive prostatic cancers.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3...ool=pubmed
Indian Journal of Urology. 2012 Jan-Mar; 28(1): 9–14.
Prostate cancer is ... the second most common cause of cancer death in the United States.[1]
Prostate cancer is the most common cancer in American men except for non-melanoma skin cancer. In the United States, an estimated 217,730 cases will be diagnosed in 2010 and 32,050 deaths will occur.[1] Its frequency has increased in part due to the widespread availability of serum PSA testing.
...the endocannabinoid signaling system has recently been the focus of medical research and considered a potential therapeutic target[15–17] since the late 1980s when Howlett and colleagues[3] identified and characterized the distinct cannabinoid receptor in rat brain.
In 2005, Sarfaraz and colleagues[30] showed increased expression of both CB1 and CB2 receptors in cultured prostate cancer cells when compared with normal prostate cells, treatment of prostate cancer cells with cannabinoid CB1/CB2 agonist WIN-55,212-2 results in a dose and time dependent decrease in cell viability ,and increased apoptosis along with decrease in androgen receptor protein expression, PSA expression, and secreted PSA, suggesting that cannabinoids should be considered as agents for the management of prostate cancer.
http://www.ncbi.nlm.nih.gov/pubmed/22594963
British Journal of Pharmacology. 2013 Jan;168(1):79-102. doi: 10.1111/j.1476-5381.2012.02027.x.
Non-THC cannabinoids inhibit prostate carcinoma growth in vitro and in vivo: pro-apoptotic effects and underlying mechanisms.
KEY RESULTS: Cannabidiol (CBD) significantly inhibited cell viability. ... CBD-BDS (i.p.) potentiated the effects of bicalutamide and docetaxel against LNCaP and DU-145 xenograft tumours and, given alone, reduced LNCaP xenograft size. CBD (1-10 µM) induced apoptosis and induced markers of intrinsic apoptotic pathways (PUMA and CHOP expression and intracellular Ca(2+)).
CONCLUSIONS AND IMPLICATIONS: These data support the clinical testing of CBD against prostate carcinoma.
Colon/rectal cancer
http://www.ncbi.nlm.nih.gov/pubmed/22231745
Journal of Molecular Medicine (Berl). 2012 Aug;90(8) :925-34. doi: 10.1007/s00109-011-0856-x. Epub 2012 Jan 10.
Chemopreventive effect of the non-psychotropic phytocannabinoid cannabidiol on experimental colon cancer.
Colon cancer affects millions of individuals in Western countries. Cannabidiol, a safe and non-psychotropic ingredient of Cannabis sativa, exerts pharmacological actions (antioxidant and intestinal antinflammatory) and mechanisms (inhibition of endocannabinoid enzymatic degradation) potentially beneficial for colon carcinogenesis.
In colorectal carcinoma cell lines, cannabidiol protected DNA from oxidative damage, increased endocannabinoid levels and reduced cell proliferation in a CB(1)-, TRPV1- and PPAR?-antagonists sensitive manner. It is concluded that cannabidiol exerts chemopreventive effect in vivo and reduces cell proliferation through multiple mechanisms.
Cancer of the blood
http://molpharm.aspetjournals.org/content/70/5/1612.abstract
Cannabinoid Receptor-Mediated Apoptosis Induced by R(+)-Methanandamide and Win55,212-2 Is Associated with Ceramide Accumulation and p38 Activation in Mantle Cell Lymphoma
Abstract
We have recently shown that cannabinoids induce growth inhibition and apoptosis in mantle cell lymphoma (MCL), a malignant B-cell lymphoma that expresses high levels of cannabinoid receptor types 1 and 2 (CB1 and CB2). In the current study, the role of each receptor and the signal transduction triggered by receptor ligation were investigated.
Taken together, these results suggest that concurrent ligation of CB1 and CB2 with either R(+)-MA or Win55 induces apoptosis via a sequence of events in MCL cells: accumulation of ceramide, phosphorylation of p38, depolarization of the mitochondrial membrane, and caspase activation. Although induction of apoptosis was observed in both MCL cell lines and primary MCL, normal B cells remained unaffected. The present data suggest that targeting CB1/CB2 may have therapeutic potential for the treatment of mantle cell lymphoma.
http://www.ncbi.nlm.nih.gov/pubmed/12091357
Blood. 2002 Jul 15;100(2):627-34.
Targeting CB2 cannabinoid receptors as a novel therapy to treat malignant lymphoblastic disease.
Together, the current data demonstrate that CB2 cannabinoid receptors expressed on malignancies of the immune system may serve as potential targets for the induction of apoptosis. Also, because CB2 agonists lack psychotropic effects, they may serve as novel anticancer agents to selectively target and kill tumors of immune origin.
http://www.ncbi.nlm.nih.gov/pubmed/12511587
J Clin Invest. 2003 Jan;111(1):43-50.
Inhibition of skin tumor growth and angiogenesis in vivo by activation of cannabinoid receptors.
Nonmelanoma skin cancer is one of the most common malignancies in humans.
Cannabinoid-treated tumors showed an increased number of apoptotic cells. This was accompanied by impairment of tumor vascularization, as determined by altered blood vessel morphology and decreased expression of proangiogenic factors (VEGF, placental growth factor, and angiopoietin 2). Abrogation of EGF-R function was also observed in cannabinoid-treated tumors. These results support a new therapeutic approach for the treatment of skin tumors.
Liver cancer
http://www.ncbi.nlm.nih.gov/pubmed/21475304
Cell Death Differ. 2011 Jul;18(7):1099-111. doi: 10.1038/cdd.2011.32. Epub 2011 Apr 8.
Anti-tumoral action of cannabinoids on hepatocellular carcinoma: role of AMPK-dependent activation of autophagy.
Hepatocellular carcinoma (HCC) (Liver cancer) is the third cause of cancer-related death worldwide. When these tumors are in advanced stages, few therapeutic options are available. Therefore, it is essential to search for new treatments to fight this disease. In this study, we investigated the effects of cannabinoids--a novel family of potential anticancer agents--on the growth of HCC
We found that delta(9)-tetrahydrocannabinol (delta(9)-THC, the main active component of Cannabis sativa) and JWH-015 (a cannabinoid receptor 2 (CB(2)) cannabinoid receptor-selective agonist) reduced the viability of the human HCC cell lines HepG2 (human hepatocellular liver carcinoma cell line) and HuH-7 (hepatocellular carcinoma cells), an effect that relied on the stimulation of CB(2) receptor.
In vivo studies revealed that delta(9)-THC and JWH-015 reduced the growth of HCC subcutaneous xenografts, an effect that was not evident when autophagy was genetically of pharmacologically inhibited in those tumors.
Moreover, cannabinoids were also able to inhibit tumor growth and ascites in an orthotopic model of HCC xenograft. Our findings may contribute to the design of new therapeutic strategies for the management of HCC.
Biliary tract cancer
http://www.ncbi.nlm.nih.gov/pubmed/19916793
Cancer Invest. 2010 May;28(4):357-63. doi: 10.3109/07357900903405934.
The dual effects of delta(9)-tetrahydrocannabinol on cholangiocarcinoma cells: anti-invasion activity at low concentration and apoptosis induction at high concentration.
Currently, only gemcitabine plus platinum demonstrates the considerable activity for cholangiocarcinoma. The anticancer effect of Delta (9)-tetrahydrocannabinol (THC), the principal active component of cannabinoids has been demonstrated in various kinds of cancers. We therefore evaluate the antitumor effects of THC on cholangiocarcinoma cells. Both cholangiocarcinoma cell lines and surgical specimens from cholangiocarcinoma patients expressed cannabinoid receptors.
THC inhibited cell proliferation, migration and invasion, and induced cell apoptosis. THC also decreased actin polymerization and reduced tumor cell survival in anoikis assay. pMEK1/2 and pAkt demonstrated the lower extent than untreated cells.
Consequently, THC is potentially used to retard cholangiocarcinoma cell growth and metastasis.
Cancer general
http://www.ncbi.nlm.nih.gov/pubmed/12514108
FASEB J. 2003 Mar;17(3):529-31. Epub 2003 Jan 2.
Inhibition of tumor angiogenesis by cannabinoids.
Cannabinoids, the active components of marijuana and their derivatives, induce tumor regression in rodents (8) . However, the mechanism of cannabinoid antitumoral action in vivo is as yet unknown. Here we show that local administration of a nonpsychoactive cannabinoid to mice inhibits angiogenesis of malignant gliomas as determined by immunohistochemical analyses and vascular permeability assays. In vitro and in vivo experiments show that at least two mechanisms may be involved in this cannabinoid action: the direct inhibition of vascular endothelial cell migration and survival as well as the decrease of the expression of proangiogenic factors (vascular endothelial growth factor and angiopoietin-2) and matrix metalloproteinase-2 in the tumors. Inhibition of tumor angiogenesis may allow new strategies for the design of cannabinoid-based antitumoral therapies.
http://www.ncbi.nlm.nih.gov/pubmed/15313899
Cancer Res. 2004 Aug 15;64(16):5617-23.
Cannabinoids inhibit the vascular endothelial growth factor pathway in gliomas.
Cannabinoids inhibit tumor angiogenesis in mice, but the mechanism of their antiangiogenic action is still unknown. Because the vascular endothelial growth factor (VEGF) pathway plays a critical role in tumor angiogenesis, here we studied whether cannabinoids affect it. As a first approach, cDNA array analysis showed that cannabinoid administration to mice bearing s.c. gliomas lowered the expression of various VEGF pathway-related genes. The use of other methods (ELISA, Western blotting, and confocal microscopy) provided additional evidence that cannabinoids depressed the VEGF pathway by decreasing the production of VEGF and the activation of VEGF receptor (VEGFR)-2, the most prominent VEGF receptor, in cultured glioma cells and in mouse gliomas. Cannabinoid-induced inhibition of VEGF production and VEGFR-2 activation was abrogated both in vitro and in vivo by pharmacological blockade of ceramide biosynthesis. These changes in the VEGF pathway were paralleled by changes in tumor size. Moreover, intratumoral administration of the cannabinoid Delta9-tetrahydrocannabinol to two patients with glioblastoma multiforme (grade IV astrocytoma) decreased VEGF levels and VEGFR-2 activation in the tumors. Because blockade of the VEGF pathway constitutes one of the most promising antitumoral approaches currently available, the present findings provide a novel pharmacological target for cannabinoid-based therapies.
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