Tag Archives: anti-angiogenic

Anti-Tumorigenic Properties of Omega-3 Endocannabinoid Epoxides.

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Journal of Medicinal Chemistry

“Accumulating studies have linked inflammation to tumor progression.

Dietary omega-3 fatty acids including docosahexaenoic acid (DHA) have been shown to suppress tumor growth through their conversion to epoxide metabolites. Alternatively, DHA is converted enzymatically into docosahexaenoylethanolamide (DHEA), an endocannabinoid with anti-proliferative activity.

Recently, we reported a novel class of anti-inflammatory DHEA-epoxides (EDP-EAs) that contain both ethanolamide and epoxide moieties. Herein we evaluate the anti-tumorigenic properties of EDP-EAs in an osteosarcoma model.

First, we show ~80% increase in EDP-EAs in metastatic lungs versus normal mouse lungs. We found significant differences in the apoptotic and anti-migratory potency of the different EDP-EA regioisomers, which are partly mediated through cannabinoid receptor 1 (CB1).

Furthermore, we synthesized derivatives of the most pro-apoptotic regioisomer. These derivatives had reduced hydrolytic susceptibility to fatty acid-amide hydrolase and increased CB1 binding.

Collectively, we report a novel class of EDP-EAs that exhibit anti-angiogenic, anti-tumorigenic and anti-migratory properties in osteosarcoma.”

https://www.ncbi.nlm.nih.gov/pubmed/29856219

https://pubs.acs.org/doi/10.1021/acs.jmedchem.8b00243

“Omega-3 Fatty Byproducts May Have Anticancer Effects.” https://scienceblog.com/502227/omega-3-fatty-byproducts-may-have-anticancer-effects/
“Products of omega-3 fatty acid metabolism may have anticancer effects, study shows” https://medicalxpress.com/news/2018-07-products-omega-fatty-acid-metabolism.html
“Omega-3-derived cannabinoid may stop cancer. New research suggests that the body’s natural pain-killer, the “endocannabinoid system,” may also have cancer-fighting properties when “activated” by omega-3 fatty acids.” https://www.medicalnewstoday.com/articles/322482.php
“Products of omega-3 fatty acid metabolism may have anticancer effects” https://www.sciencedaily.com/releases/2018/07/180713220137.htm

Cannabinoids: Possible agents for treatment of psoriasis via suppression of angiogenesis and inflammation.

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“Psoriasis is a chronic skin disease also affecting other sites such as joints.

This disease highly depends on inflammation and angiogenesis as well as other pathways.

At each step of the psoriasis molecular pathway, different inflammatory cytokines and angiogenic growth factors are involved such as hypoxia inducible factor-1 α (HIF-1 α), vascular endothelial growth factor (VEGF), matrix metalo proteinases (MMPs), basic fibroblast growth factor (bFGF), Angiopoitin-2, interleukin-8 (IL-8), IL-17, and IL-2. Beside the mentioned growth factors and cytokines, cellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) which play roles in both angiogenesis and inflammation are also involved in the pathogenesis.

Cannabinoids are active compounds of Cannabina Sativa inducing their effects through cannabinoid receptors (CBs).

JWH-133 is a synthetic cannabinoid with strong anti-angiogenic and anti-inflammatory activities. This agent is able to inhibit HIF-1 α, VEGF, MMPs, bFGF, IL-8, IL-17, and other mentioned cytokines and adhesion molecules both in vivo and in vitro.

Altogether, authors suggest using this cannabinoid for treatment of psoriasis due to its potential in suppressing the two main steps of psoriatic pathogenesis.

Of course complementary animal studies and human trials are still required.”

https://www.ncbi.nlm.nih.gov/pubmed/28110689

Antitumorigenic targets of cannabinoids – current status and implications.

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“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.”

http://www.ncbi.nlm.nih.gov/pubmed/27070944

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

Cannabinoid pharmacology in cancer research: A new hope for cancer patients?

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“Cannabinoids have been used for many centuries to ease pain and in the past decade, the endocannabinoid system has been implicated in a number of pathophysiological conditions, such as mood and anxiety disorders, movement disorders such as Parkinson’s and Huntington’s disease, neuropathic pain, multiple sclerosis, spinal cord injury, atherosclerosis, myocardial infarction, stroke, hypertension, glaucoma, obesity, and osteoporosis.

Several studies have demonstrated that cannabinoids also have anti-cancer activity and as cannabinoids are usually well tolerated and do not produce the typical toxic effects of conventional chemotherapies, there is considerable merit in the development of cannabinoids as potential anticancer therapies.

Whilst the presence of psychoactive effects of cannabinoids could prevent any progress in this field, recent studies have shown the value of the non-psychoactive components of cannabinoids in activating apoptotic pathways, inducing anti-proliferative and anti-angiogenic effects.

The aforementioned effects are suggested to be through pathways such as ERK, Akt, mitogen-activated protein kinase (MAPK) pathways, phosphoinositide 3-kinase (PI3K) pathways and hypoxia inducible factor 1 (HIF1), all of which are important contributors to the hallmarks of cancer.

Many important questions still remain unanswered or are poorly addressed thus necessitating further research at basic pre-clinical and clinical levels. In this review, we address these issues with a view to identifying the key challenges that future research needs to address.”

http://www.ncbi.nlm.nih.gov/pubmed/26852955

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

Δ-9 Tetrahydrocannabinol inhibits growth and metastasis of lung cancer.

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“Lung cancer is the major cause of cancer-related mortality worldwide.

Many of these over-express epidermal growth factor receptor (EGFR), and are usually highly aggressive and resistant to chemotherapy.

Recent studies have shown that Δ-9 Tetrahydrocannabinol (THC), the major component of Cannabis sativa, possess anti-tumor properties against various types of cancers.

However, not much is known about its effect on lung cancer. In this study, we sought to characterize the effect of THC on EGF-induced growth and metastasis of human non small lung cancer cell (NSCLC) lines A549 and SW-1573.

We demonstrate that these cell lines and primary tumor samples derived from lung cancer patients express cannabinoids receptors CB1 and CB2, the known targets for THC action.

We further show that THC inhibits EGF-induced growth in these cell lines.

In addition THC attenuated EGF-stimulated chemotaxis and chemoinvasion.

Next we characterized the effect of THC on in vivo lung cancer growth and metastasis in a murine model. A549 cells were implanted in SCID mice (n=6 per group) through subcutaneous and intravenous injections to generate subcutaneous and lung metastatic cancer, respectively. THC (5mg/kg body wt.) was administered once daily through intraperitoneal injections for 21 days. The mice were analyzed for tumor growth and lung metastasis.

A significant reduction (~50%) in tumor weight and volume were observed in THC treated animals compared to the vehicle treated animals.

THC treated animals also showed a significant (~60%) reduction in macroscopic lesions on the lung surface in comparison to vehicle treated control.

Immunohistochemical analysis of the tumor samples from THC treated animals revealed anti-proliferative and anti-angiogenic effects of THC with significant reduction in staining for Ki67, a proliferative marker and CD31, an endothelial marker indicative of vascularization. Investigation into the signaling events associated with reduced EGF-induced functional effects revealed that THC also inhibits EGF-induced Akt phosphorylation. Akt is a central signaling molecule of EGFR-mediated signaling pathways and it regulates a diverse array of cellular functions, including proliferation, angiogenesis, invasion and apoptosis.

Cumulatively, these studies indicate that THC has anti-tumorigenic and anti-metastatic effects against lung cancer. Novel therapies against EGFR overexpressing, aggressive and chemotherapy resistant lung cancers may include targeting the cannabinoids receptors.”

http://cancerres.aacrjournals.org/content/67/9_Supplement/4749.short

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

Cannabinoids as therapeutic agents in cancer: current status and future implications

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“Cannabinoids… active compounds of the Cannabis sativa plant… cannabinoids are clinically used for anti-palliative effects, recent studies open a promising possibility as anti-cancer agents.

They have been shown to possess anti-proliferative and anti-angiogenic effects in vitro as well as in vivo in different cancer models…”  http://www.ncbi.nlm.nih.gov/pubmed/25115386

“Cannabinoids… the active compounds of the Cannabis sativa plant… anti-cancer agents… anti-proliferative… anti-angiogenic… anti-migratory and anti-invasive… The administration of single cannabinoids might produce limited relief compared to the administration of crude extract of plant containing multiple cannabinoids, terpenes and flavanoids.” Full-text: http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B0%5D=2233&path%5B1%5D=3664

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

CANNABINOIDs INHIBIT angiogenic capacities of Endothelial cells via release of Tissue inhibitor of matrix metalloproteinases-1 from lung cancer cells.

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“Cannabinoids inhibit tumor neovascularisation as part of their tumorregressive action.

However, the underlying mechanism is still under debate. In the present study the impact of cannabinoids on potential tumor-to-endothelial cell communication conferring anti-angiogenesis was studied…

Collectively, our data suggest a pivotal role of the anti-angiogenic factor TIMP-1 inintercellular tumor-endothelial cell communication resulting in anti-angiogenic features of endothelial cells.”

http://www.ncbi.nlm.nih.gov/pubmed/24976505

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

Anti-tumor activity of the novel hexahydrocannabinol analog LYR-8 in Human colorectal tumor xenograft is mediated through the inhibition of Akt and hypoxia-inducible factor-1α activation.

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“Cannabinoid compounds have been shown to exert anti-tumor effects by affecting angiogenesis, invasion, and metastasis.

 

In the present study, we examined the action mechanism by which a novel hexahydrocannabinol analog, exerts anti-angiogenic and anti-tumor activity in human cancer xenografts.

These results indicate a novel function of cannabinoid-like compound as an anti-tumor agent.”

http://www.ncbi.nlm.nih.gov/pubmed/22687485

Inhibition of tumor angiogenesis by cannabinoids

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“Cannabinoids, the active components of marijuana and their derivatives, inhibit tumor growth in animal models… Because the generation of a new vascular supply (angiogenesis) is causally involved in the progression of the majority of solid tumors, the aim of this study was to test whether cannabinoids inhibit tumor angiogenesis.”

Figure 1.

“PRINCIPAL FINDINGS

1. Cannabinoid administration inhibits tumor angiogenesis

2. Cannabinoid administration inhibits vascular endothelial cell migration and survival

3. Cannabinoid administration inhibits tumor expression of proangiogenic factors and improves other markers of tumor malignancy

 

 …In the context of the renaissance in the study of the therapeutic effects of cannabinoids, our findings show that these compounds may be considered promising anti-tumoral agents as they inhibit tumor angiogenesis and growth in vivo with no significant side effects.

 This report provides a mechanistic basis for the anti-tumoral action of cannabinoids and a novel pharmacological target for cannabinoid-based anti-tumoral therapies…”

Full text:  http://www.fasebj.org/content/17/3/529.full

Delta–9 Tetrahydrocannabinol inhibits growth and metastasis of lung cancer – Harvard University

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“Lung cancer is the major cause of cancer-related mortality worldwide.Many of these over-express epidermal growth factor receptor(EGFR), and are usually highly aggressive and resistant to chemotherapy.

Recent studies have shown that {Delta}-9 Tetrahydrocannabinol (THC),the major component of Cannabis sativa, possess anti-tumor propertiesagainst various types of cancers.

 However, not much is knownabout its effect on lung cancer. In this study, we sought tocharacterize the effect of THC on EGF-induced growth and metastasisof human non small lung cancer cell (NSCLC) lines A549 and SW-1573.

We demonstrate that these cell lines and primary tumor samplesderived from lung cancer patients express cannabinoids receptorsCB1 and CB2, the known targets for THC action. We further showthat THC inhibits EGF-induced growth in these cell lines. Inaddition THC attenuated EGF-stimulated chemotaxis and chemoinvasion.Next we characterized the effect of THC on in vivo lung cancergrowth and metastasis in a murine model. A549 cells were implantedin SCID mice (n=6 per group) through subcutaneous and intravenousinjections to generate subcutaneous and lung metastatic cancer,respectively. THC (5mg/kg body wt.) was administered once dailythrough intraperitoneal injections for 21 days. The mice wereanalyzed for tumor growth and lung metastasis.

 A significantreduction (~50%) in tumor weight and volume were observed inTHC treated animals compared to the vehicle treated animals.THC treated animals also showed a significant (~60%) reductionin macroscopic lesions on the lung surface in comparison tovehicle treated control. Immunohistochemical analysis of thetumor samples from THC treated animals revealed anti-proliferativeand anti-angiogenic effects of THC with significant reductionin staining for Ki67, a proliferative marker and CD31, an endothelialmarker indicative of vascularization. Investigation into thesignaling events associated with reduced EGF-induced functionaleffects revealed that THC also inhibits EGF-induced Akt phosphorylation.Akt is a central signaling molecule of EGFR-mediated signalingpathways and it regulates a diverse array of cellular functions,including proliferation, angiogenesis, invasion and apoptosis.

Cumulatively, these studies indicate that THC has anti-tumorigenic and anti-metastatic effects against lung cancer. Novel therapies against EGFR overexpressing, aggressive and chemotherapy resistant lung cancers may include targeting the cannabinoids receptors.”

http://www.aacrmeetingabstracts.org/cgi/content/meeting_abstract/2007/1_Annual_Meeting/4749%20?maxtoshow&hits=80&RESULTFORMAT&fulltext=cannabinoid&searchid=1&FIRSTINDEX=1760&resourcetype=HWCIT