Cannabinoid receptor 2 (CB2) agonists and antagonists: a patent update.

May 25, 2016, 4:54 am

≫ Next: The Use of Medical Marijuana in Cancer.

≪ Previous: Effects of Delta-9-Tetrahydrocannabinol and Cannabidiol on Cisplatin-Induced Neuropathy in Mice.

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“Modulation of the CB₂ receptor is an interesting approach for pain and inflammation, arthritis, addictions, neuroprotection, and cancer, among other possible therapeutic applications, and is devoid of central side effects.

Structural diversity of CB₂ modulator scaffolds characterized the patent literature.

Several CB₂ agonists reached clinical Phase II for pain management and inflammation.

Other therapeutic applications need to be explored such as neuroprotection and/or neurodegeneration.”

http://www.ncbi.nlm.nih.gov/pubmed/27215781

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The Use of Medical Marijuana in Cancer.

May 25, 2016, 5:08 am

≫ Next: Endocannabinoid system: a promising therapeutic target for the treatment of haematological malignancies?

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“The use of medical marijuana in cancer care presents a dilemma for both patients and physicians. The scientific evidence is evolving, yet much of the known information is still insufficient to adequately inform patients as to risks and benefits. In addition, evidence-based dosing and administration information on medical marijuana is lacking. Medical marijuana is now legal, on some level, in 24 states plus the District of Columbia, yet is not legal on the federal level. This review addresses the current state of the research, including potential indications, risks and adverse effects, preliminary data on anticancer effects, as well as legal and quality issues. A summary of the clinical trials underway on medical marijuana in the oncology setting is discussed.”

http://www.ncbi.nlm.nih.gov/pubmed/27215434

Endocannabinoid system: a promising therapeutic target for the treatment of haematological malignancies?

May 31, 2016, 4:20 am

≫ Next: Phytochemicals as adjunctive with conventional anticancer therapies.

≪ Previous: The Use of Medical Marijuana in Cancer.

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“The therapeutic properties of cannabinoids are well-known since ancient years.

Growing evidence exist on endocannabinoid system (ECS) modulation related with human tumorigenesis.

Taking into account the substantial role of ECS on immune cell regulation, the present review is aimed to summarize the emerging evidence concerning cannabinoid receptor (CBR) expression and cannabinoid ligand effects on haematological malignancies.

CONCLUSIONS:

Most of cannabinoid actions, mainly CB2R-mediated against haematopoietic malignant cells, seems promising, as inhibition of cell proliferation and apoptosis and paraptosis induction have been documented.

Cannabinoid ligands appear to activate rudimentary pathways for cell survival, such as ERK, JNK, p38 MAPK, and to induce caspase synthesis, in vitro. Such data are strongly recommended to be confirmed by in vivo experiments with emphasis on cannabinoid ligands’ bioavailability and phytocannabinoid psychotropic properties.

The preliminary antitumoral ECS effects and their relative lack of important side effects render ECS a promising therapeutic target for the treatment of haematological malignancies.”

http://www.ncbi.nlm.nih.gov/pubmed/27237820

Phytochemicals as adjunctive with conventional anticancer therapies.

June 6, 2016, 5:00 am

≫ Next: Inhibition of human tumour prostate PC-3 cell growth by cannabinoids R(+)-Methanandamide and JWH-015: Involvement of CB2

≪ Previous: Endocannabinoid system: a promising therapeutic target for the treatment of haematological malignancies?

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“Cancer is defined as the abnormal proliferations of cells which could occur in any tissue and can cause life-threatening malignancies with high financial costs for both patients and health care system. Plant-derived secondary metabolites are shown to have positive role in various diseases and conditions. The aim of the present study is to summarize clinical evidences on the benefits of phytochemicals as adjuvant therapy along with conventional anticancer therapies.

The findings showed that positive effects of phytochemicals are due to their direct anti-carcinogenic activity, induction of relief in cancer complications, as well as their protective role against side effects of conventional chemotherapeutic agents.

Results obtained from current review demonstrated that numerous phytochemical agents from different chemical categories including alkaloid, benzopyran, coumarin, carotenoid, diarylheptanoid, flavonoid, indole, polysaccharide, protein, stilbene, terpene, and xanthonoid possess therapeutic effect in patients with different types of cancer. Polyphenols are the most studied components. Curcumin, ginsenosides, lycopene, homoharringtonine, aviscumine, and resveratrol are amongst the major components with remarkable volumes of clinical evidence indicating their direct anticancer activities in different types of cancer including hepatocarcinoma, prostate cancer, leukemia and lymphoma, breast and ovarian cancer, and gastrointestinal cancers.

Cannabinoids, cumarin, curcumin, ginsenosides, epigallocatechin gallate, vitexin, and salidroside are phytochemicals with significant alleviative effect on synthetic chemotherapy-induced toxicities.”

http://www.ncbi.nlm.nih.gov/pubmed/27262332

Inhibition of human tumour prostate PC-3 cell growth by cannabinoids R(+)-Methanandamide and JWH-015: Involvement of CB2

June 11, 2016, 8:59 am

≫ Next: CANNABIS CHEMICALS STOP PROSTATE CANCER GROWTH

≪ Previous: Phytochemicals as adjunctive with conventional anticancer therapies.

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“We have previously shown that cannabinoids induce growth inhibition and apoptosis in prostate cancer PC-3 cells, which express high levels of cannabinoid receptor types 1 and 2 (CB₁ and CB₂). In this study, we investigated the role of CB₂ receptor in the anti-proliferative action of cannabinoids and the signal transduction triggered by receptor ligation.

This study defines the involvement of CB₂-mediated signalling in the in vivo and in vitro growth inhibition of prostate cancer cells and suggests that CB₂ agonists have potential therapeutic interest and deserve to be explored in the management of prostate cancer.

Cannabinoids, the active components of Cannabis sativa and their derivatives, exert a wide spectrum of modulatory actions and pharmacological activities in the brain as well as in the periphery, and therefore, the therapeutic potential of cannabinoids has gained much attention during the past few years. One of the most exciting areas of current research in the therapeutic potential of cannabinoids is cancer.

Recent evidence suggests that cannabinoids are powerful regulators of cell growth and differentiation. They have been shown to exert anti-tumoural effects by decreasing viability, proliferation, adhesion and migration on various cancer cells, thereby suggesting the potential use of cannabinoids in the treatment of gliomas, prostate and breast cancers and malignancies of immune origin.

Overall, our data show a role for the cannabinoid receptor CB₂ in the anti-tumour effect of cannabinoids on prostate cells in vitroand in vivo. There is considerable interest in the application of selective CB₂ receptor agonists, which are devoid of typical marijuana-like psychoactive properties of CB₁ agonists, for future cannabinoid-based anticancer therapies. Therefore, our findings point to the potential application of cannabinoid receptor type 2 ligands as anti-tumour agents in prostate cancer.”

 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2743360/

http://www.thctotalhealthcare.com/category/prostate-cancer/

CANNABIS CHEMICALS STOP PROSTATE CANCER GROWTH

June 11, 2016, 9:03 am

≫ Next: The cannabinoid WIN 55,212-2 prevents neuroendocrine differentiation of LNCaP prostate cancer cells.

≪ Previous: Inhibition of human tumour prostate PC-3 cell growth by cannabinoids R(+)-Methanandamide and JWH-015: Involvement of CB2

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“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.

“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.””

http://www.nature.com/bjc/press_releases/p_r_aug09_6605248.html

The cannabinoid WIN 55,212-2 prevents neuroendocrine differentiation of LNCaP prostate cancer cells.

June 23, 2016, 4:30 am

≫ Next: Cannabimimetic Drugs: Recent Patents in Central Nervous System Disorders.

≪ Previous: CANNABIS CHEMICALS STOP PROSTATE CANCER GROWTH

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“Neuroendocrine (NE) differentiation represents a common feature of prostate cancer and is associated with accelerated disease progression and poor clinical outcome. Nowadays, there is no treatment for this aggressive form of prostate cancer.

The aim of this study was to determine the influence of the cannabinoid WIN 55,212-2 (WIN, a non-selective cannabinoid CB1 and CB2 receptor agonist) on the NE differentiation of prostate cancer cells.

Taken together, we demonstrate that PI3K/Akt/AMPK might be an important axis modulating NE differentiation of prostate cancer that is blocked by the cannabinoid WIN, pointing to a therapeutic potential of cannabinoids against NE prostate cancer.”

http://www.ncbi.nlm.nih.gov/pubmed/27324222

Cannabimimetic Drugs: Recent Patents in Central Nervous System Disorders.

June 24, 2016, 4:41 am

≫ Next: Activation of the orphan receptor GPR55 by lysophosphatidylinositol promotes metastasis in triple-negative breast cancer.

≪ Previous: The cannabinoid WIN 55,212-2 prevents neuroendocrine differentiation of LNCaP prostate cancer cells.

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“Agents acting via cannabinoid receptors have been widely developed; starting from the chemical structure of phytocannabinoids isolated from cannabis sativa plant, specific and selective compounds of these receptors have been produced ranging from partial to full agonists and /or antagonists endowed with different potency.

The enhanced interest on developing such classes of drugs is due to the beneficial properties widely reported by both anecdotal reports and scientific studies describing the potential medicinal use of cannabinoids and their derivatives in numerous pathological conditions in both in vitro and in vivo models.

The use of these drugs has been found to be of benefit in a wide number of neurological and neuropsychiatric disorders, and in many other diseases ranging from cancer, atherosclerosis, stroke, hypertension, inflammatory related disorders, and autoimmune diseases, just to mention some.

In particular, being the cannabinoid CB1 receptor a central receptor expressed by neurons of the central nervous system, the attention for the treatment of neurological diseases has been mainly focused on compounds acting via this receptor, however some of these compounds has been showed to act by alternative pathways in some cases unrelated to CB1 receptors.

Nonetheless, endocannabinoids are potent regulators of the synaptic function in the central nervous system and their levels are modulated in neurological diseases.

In this study, we focused on endocannabinoid mechanism of action in neuronal signaling and on cannabimimetic drug potential application in neurological disorders.

Finally, novel patents on cannabis-based drugs with applicability in central nervous system disorders are highlighted, to suggest future potential therapeutic utility of derivatives of this ancient plant.”

http://www.ncbi.nlm.nih.gov/pubmed/27334611

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Activation of the orphan receptor GPR55 by lysophosphatidylinositol promotes metastasis in triple-negative breast cancer.

June 29, 2016, 4:21 am

≫ Next: Cannabinoid signalling in glioma cells

≪ Previous: Cannabimimetic Drugs: Recent Patents in Central Nervous System Disorders.

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“The orphan G protein-coupled receptor GPR55 has been directly or indirectly related to basic alterations that drive malignant growth: uncontrolled cancer cell proliferation, sustained angiogenesis, and cancer cell adhesion and migration. However, little is known about the involvement of this receptor in metastasis.

Here, we show that elevated GPR55 expression in human tumors is associated with the aggressive basal/triple-negative breast cancer population, higher probability to develop metastases, and therefore poor patient prognosis. Activation of GPR55 by its proposed endogenous ligand lysophosphatidylinositol confers pro-invasive features on breast cancer cells both in vitro and in vivo. Specifically, this effect is elicited by coupling to Gq/11 heterotrimeric proteins and the subsequent activation, through ERK, of the transcription factor ETV4/PEA3.

Together, these data show that GPR55 promotes breast cancer metastasis, and supports the notion that this orphan receptor may constitute a new therapeutic target and potential biomarker in the highly aggressive triple-negative subtype.”

http://www.ncbi.nlm.nih.gov/pubmed/27340777

Cannabinoid signalling in glioma cells

July 9, 2016, 4:26 am

≫ Next: Anticancer and antioxidant properties of terpinolene in rat brain cells.

≪ Previous: Activation of the orphan receptor GPR55 by lysophosphatidylinositol promotes metastasis in triple-negative breast cancer.

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“Cannabinoids, originally derived from Cannabis sativa, as well as their endogenous and synthetic counterparts, were shown to induce apoptosis of glioma cells in vitro and tumour regression in vivo via their specific receptors, cannabinoid receptors CB1 and/or CB2.

CB2 are abnormally expressed in human gliomas and glioma cell lines. Most of the analysed gliomas expressed significant levels of CB2 receptor and the extent of CB2 expression in the tumour specimens was related to tumour malignancy.

A synthetic cannabinoid, WIN 55,212-2, down-regulated the Akt and Erk signalling pathways in C6 glioma cells that resulted in reduction of phosphorylated Bad levels, mitochondrial depolarization and activation of caspase cascade leading to apoptosis.

We examined whether synthetic cannabinoids with different receptor specificity: WIN55,212-2 (a non-selective CB1/CB2 agonist) and JWH133 (a CB2-selective agonist) affect survival of four human glioma cell lines and three primary human glioma cell lines.

WIN-55,212-2 decreased cell viability in all examined cell lines and induced cell death. Susceptibility of the cells to JWH133 treatment correlated with the CB2 expression. Cannabinoids triggered a decrease of mitochondrial membrane potential, cleavage of caspase-9 and effector caspases.

Induction of cell death by cannabinoid treatment led to the generation of a pro-apoptotic sphingolipid ceramide and disruption of signalling pathways crucial for regulation of proliferation and survival. Increased ceramide levels induced ER-stress and autophagy in drug-treated glioblastoma cells.

We conclude that cannabinoids are efficient inhibitors of human glioma cells growth, once the cells express specific type of cannabinoid receptor.”

http://springerplus.springeropen.com/articles/10.1186/2193-1801-4-S1-L11

Anticancer and antioxidant properties of terpinolene in rat brain cells.

July 12, 2016, 7:32 am

≫ Next: Cannabinoids for Symptom Management and Cancer Therapy: The Evidence.

≪ Previous: Cannabinoid signalling in glioma cells

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“Terpinolene (TPO) is a natural monoterpene present in essential oils of many aromatic plant species.

Our findings clearly demonstrate that TPO is a potent antiproliferative agent for brain tumour cells and may have potential as an anticancer agent, which needs to be further studied.” http://www.ncbi.nlm.nih.gov/pubmed/24084350

“Three different medicinal cannabis varieties were investigated Bedrocan, Bedrobinol and Bediol. The major components in Bedrocan smoke were Delta(9)-THC, cannabinol (CBN), terpinolene, CBG, myrcene and cis-ocimene in Bedrobinol Delta(9)-THC, CBN and myrcene in Bediol CBD, Delta(9)-THC, CBN, myrcene, CBC and terpinolene.”  http://www.ncbi.nlm.nih.gov/pubmed/20118579

“The sedative effect of inhaled terpinolene in mice and its structure-activity relationships.” http://www.ncbi.nlm.nih.gov/pubmed/23339024

 “Anticancer and antioxidant properties of terpinolene in rat brain cells.”  http://www.ncbi.nlm.nih.gov/pubmed/24084350

Cannabinoids for Symptom Management and Cancer Therapy: The Evidence.

July 14, 2016, 3:54 pm

≫ Next: 5-lipoxygenase mediates docosahexaenoyl ethanolamide and N-arachidonoyl-L-alanine-induced reactive oxygen species production and inhibition of proliferation of head and neck squamous cell carcinoma cells.

≪ Previous: Anticancer and antioxidant properties of terpinolene in rat brain cells.

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“Cannabinoids bind not only to classical receptors (CB1 and CB2) but also to certain orphan receptors (GPR55 and GPR119), ion channels (transient receptor potential vanilloid), and peroxisome proliferator-activated receptors. Cannabinoids are known to modulate a multitude of monoamine receptors. Structurally, there are 3 groups of cannabinoids.

Multiple studies, most of which are of moderate to low quality, demonstrate that tetrahydrocannabinol (THC) and oromucosal cannabinoid combinations of THC and cannabidiol (CBD) modestly reduce cancer pain.

Dronabinol and nabilone are better antiemetics for chemotherapy-induced nausea and vomiting (CINV) than certain neuroleptics, but are not better than serotonin receptor antagonists in reducing delayed emesis, and cannabinoids have largely been superseded by neurokinin-1 receptor antagonists and olanzapine; both cannabinoids have been recommended for breakthrough nausea and vomiting among other antiemetics. Dronabinol is ineffective in ameliorating cancer anorexia but does improve associated cancer-related dysgeusia.

Multiple cancers express cannabinoid receptors directly related to the degree of anaplasia and grade of tumor.

Preclinical in vitro and in vivo studies suggest that cannabinoids may have anticancer activity.

Paradoxically, cannabinoid receptor antagonists also have antitumor activity.

There are few randomized smoked or vaporized cannabis trials in cancer on which to judge the benefits of these forms of cannabinoids on symptoms and the clinical course of cancer. Smoked cannabis has been found to contain Aspergillosis. Immunosuppressed patients should be advised of the risks of using “medical marijuana” in this regard.”

http://www.ncbi.nlm.nih.gov/pubmed/27407130

5-lipoxygenase mediates docosahexaenoyl ethanolamide and N-arachidonoyl-L-alanine-induced reactive oxygen species production and inhibition of proliferation of head and neck squamous cell carcinoma cells.

July 16, 2016, 4:07 am

≫ Next: Endocannabinoid system as a regulator of tumor cell malignancy – biological pathways and clinical significance

≪ Previous: Cannabinoids for Symptom Management and Cancer Therapy: The Evidence.

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“Endocannabinoids have recently drawn attention as promising anti-cancer agents.

We previously observed that anandamide (AEA), one of the representative endocannabinoids, effectively inhibited the proliferation of head and neck squamous cell carcinoma (HNSCC) cell lines in a receptor-independent manner.

In this study, using HNSCC cell lines, we examined the anti-cancer effects and the mechanisms of action of docosahexaenoyl ethanolamide (DHEA) and N-arachidonoyl-L-alanine (NALA), which are polyunsaturated fatty acid (PUFA)-based ethanolamides like AEA.

From these findings, we suggest that ROS production induced by the 5-LO pathway mediates the anti-cancer effects of DHEA and NALA on HNSCC cells.

Finally, our findings suggest the possibility of a new cancer-specific therapeutic strategy, which utilizes 5-LO activity rather than inhibiting it.”

http://www.ncbi.nlm.nih.gov/pubmed/27411387

Endocannabinoid system as a regulator of tumor cell malignancy – biological pathways and clinical significance

July 19, 2016, 11:28 am

≫ Next: In vitro and in vivo evaluation of Δ⁹-tetrahidrocannabinol/PLGA nanoparticles for cancer chemotherapy.

≪ Previous: 5-lipoxygenase mediates docosahexaenoyl ethanolamide and N-arachidonoyl-L-alanine-induced reactive oxygen species production and inhibition of proliferation of head and neck squamous cell carcinoma cells.

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“The endocannabinoid system (ECS) comprises cannabinoid receptors (CBs), endogenous cannabinoids, and enzymes responsible for their synthesis, transport, and degradation of (endo)cannabinoids.

To date, two CBs, CB1 and CB2, have been characterized; however, orphan G-protein-coupled receptor GPR55 has been suggested to be the third putative CB.

Several different types of cancer present abnormal expression of CBs, as well as other components of ECS, and this has been shown to correlate with the clinical outcome.

Although most effects of (endo)cannabinoids are mediated through stimulation of classical CBs, they also interact with several molecules, either prosurvival or proapoptotic molecules.

It should be noted that the mode of action of exogenous cannabinoids differs significantly from that of endocannabinoid and results from the studies on their activity both in vivo and in vitro could not be easily compared.

This review highlights the main signaling pathways involved in the antitumor activity of cannabinoids and the influence of their activation on cancer cell biology.

We also discuss changes in the expression pattern of the ECS in various cancer types that have an impact on disease progression and patient survival.

A growing amount of experimental data imply possible exploitation of cannabinoids in cancer therapy.”

https://www.dovepress.com/endocannabinoid-system-as-a-regulator-of-tumor-cell-malignancy-ndash-b-peer-reviewed-article-OTT

In vitro and in vivo evaluation of Δ⁹-tetrahidrocannabinol/PLGA nanoparticles for cancer chemotherapy.

August 1, 2016, 1:43 pm

≫ Next: Preparation and characterization of Δ(9)-tetrahydrocannabinol-loaded biodegradable polymeric microparticles and their antitumoral efficacy on cancer cell lines.

≪ Previous: Endocannabinoid system as a regulator of tumor cell malignancy – biological pathways and clinical significance

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“Nanoplatforms can optimize the efficacy and safety of chemotherapy, and thus cancer therapy. However, new approaches are encouraged in developing new nanomedicines against malignant cells.

In this work, a reproducible methodology is described to prepare Δ(9)-tetrahidrocannabinol (Δ(9)-THC)-loaded poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles against lung cancer.

Cell viability studies comparing the activity of the nanoformulations against human A-549 and murine LL2 lung adenocarcinoma cells, and human embryo lung fibroblastic MRC-5 cells revealed a statistically significant selective cytotoxic effect toward the lung cancer cell lines.

In addition, cytotoxicity assays in A-549 cells demonstrated the more intense anticancer activity of Δ(9)-THC-loaded PEGylated PLGA nanoparticles.

These promising results were confirmed by in vivo studies in LL2 lung tumor-bearing immunocompetent C57BL/6 mice.”

http://www.ncbi.nlm.nih.gov/pubmed/25899283

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Preparation and characterization of Δ(9)-tetrahydrocannabinol-loaded biodegradable polymeric microparticles and their antitumoral efficacy on cancer cell lines.

August 1, 2016, 2:18 pm

≫ Next: Endocannabinoid system as a regulator of tumor cell malignancy – biological pathways and clinical significance.

≪ Previous: In vitro and in vivo evaluation of Δ⁹-tetrahidrocannabinol/PLGA nanoparticles for cancer chemotherapy.

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“Cannabinoids present an interesting therapeutic potential as antiemetics, appetite stimulants in debilitating diseases (cancer, AIDS and multiple sclerosis), analgesics, and in the treatment of multiple sclerosis and cancer, among other conditions.

However, despite their high clinical potential, only few dosage forms are available to date.

In this paper, the development of Δ(9)-tetrahydrocannabinol (THC) biodegradable microspheres as an alternative delivery system for cannabinoid parenteral administration is proposed.

As THC has shown therapeutic potential as anticancer drug, the efficacy of the microspheres was tested on different cancer cell lines.

Interestingly, the microspheres were able to inhibit cancer cell proliferation during the nine-day study period.

All the above results suggest that the use of biodegradable microspheres would be a suitable alternative delivery system for THC administration.”

http://www.ncbi.nlm.nih.gov/pubmed/23773072

Endocannabinoid system as a regulator of tumor cell malignancy – biological pathways and clinical significance.

August 4, 2016, 5:49 am

≫ Next: Modulation of L-α-lysophosphatidylinositol/GPR55 mitogen-activated protein kinase (MAPK) signaling by cannabinoids.

≪ Previous: Preparation and characterization of Δ(9)-tetrahydrocannabinol-loaded biodegradable polymeric microparticles and their antitumoral efficacy on cancer cell lines.

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“The endocannabinoid system (ECS) comprises cannabinoid receptors (CBs), endogenous cannabinoids, and enzymes responsible for their synthesis, transport, and degradation of (endo)cannabinoids.

To date, two CBs, CB1 and CB2, have been characterized; however, orphan G-protein-coupled receptor GPR55 has been suggested to be the third putative CB.

Several different types of cancer present abnormal expression of CBs, as well as other components of ECS, and this has been shown to correlate with the clinical outcome.

Although most effects of (endo)cannabinoids are mediated through stimulation of classical CBs, they also interact with several molecules, either prosurvival or proapoptotic molecules.

It should be noted that the mode of action of exogenous cannabinoids differs significantly from that of endocannabinoid and results from the studies on their activity both in vivo and in vitro could not be easily compared.

This review highlights the main signaling pathways involved in the antitumor activity of cannabinoids and the influence of their activation on cancer cell biology.

We also discuss changes in the expression pattern of the ECS in various cancer types that have an impact on disease progression and patient survival.

A growing amount of experimental data imply possible exploitation of cannabinoids in cancer therapy.”

http://www.ncbi.nlm.nih.gov/pubmed/27486335

Modulation of L-α-lysophosphatidylinositol/GPR55 mitogen-activated protein kinase (MAPK) signaling by cannabinoids.

August 5, 2016, 11:26 am

≫ Next: Inhibition of interleukin-8 release in the human colonic epithelial cell line HT-29 by cannabinoids.

≪ Previous: Endocannabinoid system as a regulator of tumor cell malignancy – biological pathways and clinical significance.

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“This study has implications for developing new therapeutics for the treatment of cancer, pain, and metabolic disorders.

GPR55 is activated by l-α-lysophosphatidylinositol (LPI) but also by certain cannabinoids.

In this study, we investigated the GPR55 pharmacology of various cannabinoids, including analogues of the CB1 receptor antagonist Rimonabant®, CB2 receptor agonists, and Cannabis sativa constituents.

Here, we show that CB1 receptor antagonists can act both as agonists alone and as inhibitors of LPI signaling under the same assay conditions. This study clarifies the controversy surrounding the GPR55-mediated actions of SR141716A; some reports indicate the compound to be an agonist and some report antagonism. In contrast, we report that the CB2 ligand GW405833 behaves as a partial agonist of GPR55 alone and enhances LPI signaling. GPR55 has been implicated in pain transmission, and thus our results suggest that this receptor may be responsible for some of the antinociceptive actions of certain CB2 receptor ligands.

Here, we report that the little investigated cannabis constituents CBDV, CBGA, and CBGV are potent inhibitors of LPI-induced GPR55 signaling.

The phytocannabinoids Δ9-tetrahydrocannabivarin, cannabidivarin, and cannabigerovarin are also potent inhibitors of LPI.

Our findings also suggest that GPR55 may be a new pharmacological target for the following C. sativa constituents: Δ⁹-THCV, CBDV, CBGA, and CBGV.

These Cannabis sativa constituents may represent novel therapeutics targeting GPR55.”  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3249141/

“Lysophosphatidylinositol (LPI) is a bioactive lipid generated by phospholipase A2 which is believed to play an important role in several diseases.”  http://www.ncbi.nlm.nih.gov/pubmed/22285325

 “The putative cannabinoid receptor GPR55 promotes cancer cell proliferation.  In this issue of Oncogene, two groups demonstrated that GPR55 is expressed in various cancer types in an aggressiveness-related manner, suggesting a novel cancer biomarker and a potential therapeutic target.” http://www.ncbi.nlm.nih.gov/pubmed/21057532

“The orphan G protein-coupled receptor GPR55 promotes cancer cell proliferation via ERK. These findings reveal the importance of GPR55 in human cancer, and suggest that it could constitute a new biomarker and therapeutic target in oncology.” http://www.ncbi.nlm.nih.gov/pubmed/20818416

“The putative cannabinoid receptor GPR55 defines a novel autocrine loop in cancer cell proliferation. These findings may have important implications for LPI as a novel cancer biomarker and for its receptor GPR55 as a potential therapeutic target.”  http://www.ncbi.nlm.nih.gov/pubmed/20838378

“L-α-lysophosphatidylinositol meets GPR55: a deadly relationship. Evidence points to a role of L-α-lysophosphatidylinositol (LPI) in cancer.”  http://www.ncbi.nlm.nih.gov/pubmed/21367464

Inhibition of interleukin-8 release in the human colonic epithelial cell line HT-29 by cannabinoids.

August 5, 2016, 12:38 pm

≫ Next: Cannabinoids As Potential Treatment for Chemotherapy-Induced Nausea and Vomiting.

≪ Previous: Modulation of L-α-lysophosphatidylinositol/GPR55 mitogen-activated protein kinase (MAPK) signaling by cannabinoids.

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“We have investigated the effects of cannabinoid agonists and antagonists on tumour necrosis factor-alpha (TNF-alpha)-induced secretion of interleukin-8 from the colonic epithelial cell line, HT-29.

The cannabinoid receptor agonists [(-)-3-[2-hydroxy-4-(1,1-dimethyl-heptyl)-phenyl]4-[3-hydroxypropyl]cyclo-hexan-1-ol] (CP55,940); Delta-9-tetrahydrocannabinol; [R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl) methyl] pyrrolo[1,2,3-de]1,4-benzoxazin-6-yl](1-naphthyl) methanone mesylate] (WIN55,212-2) and 1-propyl-2-methyl-3-naphthoyl-indole (JWH 015) inhibited TNF-alpha induced release of interleukin-8 in a concentration-dependent manner.

We conclude that in HT-29 cells, TNF-alpha-induced interleukin-8 release is inhibited by cannabinoids through activation of cannabinoid CB(2) receptors.”

http://www.ncbi.nlm.nih.gov/pubmed/12498928

“Essential involvement of interleukin-8 (IL-8) in acute inflammation.”  http://www.ncbi.nlm.nih.gov/pubmed/7964163

“Interleukin-8 (IL-8) is known to possess tumorigenic and proangiogenic properties. Overexpression of IL-8 has been detected in many human tumors, including colorectal cancer (CRC). IL-8 promotes tumor growth, metastasis, chemoresistance and angiogenesis, implying IL-8 to be an important therapeutic target in CRC.”  http://www.ncbi.nlm.nih.gov/pubmed/20648559

Cannabinoids As Potential Treatment for Chemotherapy-Induced Nausea and Vomiting.

August 11, 2016, 4:37 am

≫ Next: Cancer is a Preventable Disease that Requires Major Lifestyle Changes

≪ Previous: Inhibition of interleukin-8 release in the human colonic epithelial cell line HT-29 by cannabinoids.

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“Despite the advent of classic anti-emetics, chemotherapy-induced nausea is still problematic, with vomiting being somewhat better managed in the clinic.

If post-treatment nausea and vomiting are not properly controlled, anticipatory nausea-a conditioned response to the contextual cues associated with illness-inducing chemotherapy-can develop. Once it develops, anticipatory nausea is refractive to current anti-emetics, highlighting the need for alternative treatment options.

One of the first documented medicinal uses of Δ(9)-tetrahydrocannabinol (Δ(9)-THC) was for the treatment of chemotherapy-induced nausea and vomiting (CINV), and recent evidence is accumulating to suggest a role for the endocannabinoid system in modulating CINV.

Here, we review studies assessing the therapeutic potential of cannabinoids and manipulations of the endocannabinoid system in human patients and pre-clinical animal models of nausea and vomiting.”

http://www.ncbi.nlm.nih.gov/pubmed/27507945