“Cannabis sativa L. (Cannabaceae) is one of the first plants cultivated by man and one of the oldest plant sources of fibre, food and remedies. Cannabinoids comprise the plant‐derived compounds and their synthetic derivatives as well as endogenously produced lipophilic mediators. Phytocannabinoids are terpenophenolic secondary metabolites predominantly produced in CannabissativaL. The principal active constituent is delta‐9‐tetrahydrocannabinol (THC), which binds to endocannabinoid receptors to exert its pharmacological activity, including psychoactive effect. The other important molecule of current interest is non‐psychotropic cannabidiol (CBD). Since 1970s, phytocannabinoids have been known for their palliative effects on some cancer‐associated symptoms such as nausea and vomiting reduction, appetite stimulation and pain relief. More recently, these molecules have gained special attention for their role in cancer cell proliferation and death. A large body of evidence suggests that cannabinoids affect multiple signalling pathways involved in the development of cancer, displaying an anti‐proliferative, proapoptotic, anti‐angiogenic and anti‐metastatic activity on a wide range of cell lines and animal models of cancer.” https://www.intechopen.com/books/natural-products-and-cancer-drug-discovery/phytochemical-aspects-and-therapeutic-perspective-of-cannabinoids-in-cancer-treatment]]>
Tag Archives: antimetastatic
Cannabis sativa Extract Reduces Cytoskeletal Associated Proteins in Breast Cancer Cell Line
Inhibition of Wnt/β-Catenin pathway and Histone acetyltransferase activity by Rimonabant: a therapeutic target for colon cancer.
“In a high percentage (≥85%) of both sporadic and familial adenomatous polyposis forms of colorectal cancer (CRC), the inactivation of the APC tumor suppressor gene initiates tumor formation and modulates the Wnt/β-Catenin transduction pathways involved in the control of cell proliferation, adhesion and metastasis.
Increasing evidence showed that the endocannabinoids control tumor growth and progression, both in vitro and in vivo.
We evaluated the effect of Rimonabant, a Cannabinoid Receptor 1 (CB1) inverse agonist, on the Wnt/β-Catenin pathway in HCT116 and SW48 cell lines carrying the genetic profile of metastatic CRC poorly responsive to chemotherapies.
Obtained data heavily supported the rationale for the use of cannabinoids in combined therapies for metastatic CRC harbouring activating mutations of β-Catenin.”
https://www.ncbi.nlm.nih.gov/pubmed/28916833
https://www.nature.com/articles/s41598-017-11688-x
Cannabidiol, a novel inverse agonist for GPR12.
“GPR12 is a constitutively active, Gs protein-coupled receptor that currently has no confirmed endogenous ligands. GPR12 may be involved in physiological processes such as maintenance of oocyte meiotic arrest and brain development, as well as pathological conditions such as metastatic cancer. In this study, the potential effects of various classes of cannabinoids on GPR12 were tested using a cAMP accumulation assay. Our data demonstrate that cannabidiol (CBD), a major non-psychoactive phytocannabinoid, acted as an inverse agonist to inhibit cAMP accumulation stimulated by the constitutively active GPR12. Thus, GPR12 is a novel molecular target for CBD. CBD is a promising novel therapeutic agent for cancer, and GPR12 has been shown to alter viscoelasticity of metastatic cancer cells. Since we have demonstrated that CBD is an inverse agonist for GPR12, this provides novel mechanism of action for CBD, and an initial chemical scaffold upon which highly potent and efficacious agents acting on GPR12 may be developed with the ultimate goal of blocking cancer metastasis.” https://www.ncbi.nlm.nih.gov/pubmed/28888984 http://www.sciencedirect.com/science/article/pii/S0006291X1731759X]]>
Antitumorigenic targets of cannabinoids – current status and implications.
“Molecular structures of the endocannabinoid system have gained interest as potential pharmacotherapeutical targets for systemic cancer treatment.
The present review covers the contribution of the endocannabinoid system to cancer progression. Particular focus will be set on the accumulating preclinical data concerning antimetastatic, anti-invasive and anti-angiogenic mechanisms induced by cannabinoids.
Expert opinion: The main goal of targeting endocannabinoid structures for systemic anticancer treatment is the comparatively good safety profile of cannabinoid compounds.
In addition, antitumorigenic mechanisms of cannabinoids are not restricted to a single molecular cascade but involve multiple effects on various levels of cancer progression such as angiogenesis and metastasis. Particularly the latter effect has gained interest for pharmacological interventions.
Thus, drugs aiming at the endocannabinoid system may represent potential “antimetastatics” for an upgrade of a future armamentarium against cancer diseases.”
Effects of cannabinoids and their receptors on viral infections.
“Cannabinoids, the active ingredient in marijuana, and their derivatives have received remarkable attention in the last two decades because they can affect tumor growth and metastasis.
There is a large body of evidence from in vivo and in vitro models showing that cannabinoids and their receptors influence the immune system, viral pathogenesis, and viral replication.
The present study reviews current insights into the role of cannabinoids and their receptors on viral infections.
The results reported here indicate that cannabinoids and their receptors have different sequels for viral infection.
Although activation or inhibition of cannabinoid receptors in the majority of viral infections are proper targets for development of safe and effective treatments, caution is required before using pharmaceutical cannabinoids as a treatment agent for patients with viral infections.”
New insights into antimetastatic and antiangiogenic effects of cannabinoids.
“Cannabinoids exert antitumorigenic effects via multiple mechanisms.
Of these, antimetastatic and antiangiogenic actions have attracted considerable interest in the past years…
This chapter reviews the cell- and substance-specific antitumorigenic mechanisms of cannabinoids with particular consideration of their antimetastatic/anti-invasive and antiangiogenic actions.
In addition, beneficial interactions of cannabinoids with currently used chemotherapeutics as well as the influence of cannabinoids on tumor-immune surveillance are addressed.
Collectively, the currently available data suggest cannabinoids as a potential tool in modern cancer pharmacotherapy.”
COX-2 and PPAR-γ confer cannabidiol-induced apoptosis of human lung cancer cells.
“Within the last decade, evidence has been accumulated to suggest an antitumorigenic action of cannabinoids elicited via induction of apoptosis and alternative anticarcinogenic mechanisms… cannabidiol has been shown to elicit pronounced proapoptotic or autophagic effects on different types of tumor cells
This study investigates the role of COX-2 and PPAR-γ in cannabidiol’s proapoptotic and tumor-regressive action. In lung cancer cell lines (A549, H460) and primary cells from a patient with lung cancer, cannabidiol elicited decreased viability associated with apoptosis… our data show a novel proapoptotic mechanism of cannabidiol involving initial upregulation of COX-2 and PPAR-γ…
Collectively, our data strengthen the notion that activation of PPAR-γ may present a promising target for lung cancer therapy.
In addition and to the best of our knowledge, this is the first report to provide an inhibitor-proven tumor-regressive mechanism of cannabidiolin vivo as well as a proapoptotic mechanism confirmed by use of primary lung tumor cells.
Against this background and considering recent findings supporting a profound antimetastatic action of cannabidiol, this cannabinoid may represent a promising anticancer drug.”
Systematic review of the literature on clinical and experimental trials on the antitumor effects of cannabinoids in gliomas.
“To evaluate, through a systematic review of the literature, the antitumoral effects of cannabinoids on gliomas…
In all experimental studies included, cannabinoids exerted antitumoral activity in vitro and/or antitumoral evidence in vivo in several models of tumor cells and tumors.
The antitumor activity included: antiproliferative effects (cell cycle arrest), decreased viability and cell death by toxicity, apoptosis, necrosis, autophagy, as well as antiangiogenic and antimigratory effects.
Antitumoral evidence included: reduction in tumor size, antiangiogenic, and antimetastatic effects.
Additionally, most of the studies described that the canabinnoids exercised selective antitumoral action in several distinct tumor models. Thereby, normal cells used as controls were not affected.
The safety factor in the cannabinoids’ administration has also been demonstrated in vivo.
The various cannabinoids tested in multiple tumor models showed antitumoral effects both in vitro and in vivo.
These findings indicate that cannabinoids are promising compounds for the treatment of gliomas.”
Cannabinoids can inhibit tumor cell growth in highly invasive cancers
“A new study has found that Cannabinoids, the active components in marijuana, may aid in inhibiting tumor cell growth in highly invasive cancers.”
“Although, Cannabinoids are used in reducing the side effects of cancer treatment, such as pain, weight loss, and vomiting, evidences indicate that they might even help in suppressing tumor invasion.
Robert Ramer, Ph.D., and Burkhard Hinz, Ph.D., of the University of Rostock in Germany investigated whether and by what mechanism cannabinoids hold back tumor cell invasion.
It was found that Cannabinoids did suppress tumor cell invasion and stimulated TIMP-1 expression.
TIMP-1 is an inhibitor of a group of enzymes involved in tumor cell invasion.
“To our knowledge, this is the first report of TIMP-1-dependent anti-invasive effects of cannabinoids,” the authors said.
They added: “This signaling pathway may play an important role in the antimetastatic action of cannabinoids, whose potential therapeutic benefit in the treatment of highly invasive cancers should be addressed in clinical trials.”
The study was published in the Journal of the National Cancer Institute (ANI)”
“Inhibition of Cancer Cell Invasion by Cannabinoids via Increased Expression of Tissue Inhibitor of Matrix Metalloproteinases-1” http://jnci.oxfordjournals.org/content/100/1/59.long
http://www.topnews.in/health/cannabinoids-can-inhibit-tumor-cell-growth-highly-invasive-cancers-2380