The therapeutic aspects of the endocannabinoid system (ECS) for cancer and their development: from nature to laboratory.

Posted on December 15, 2015 by David

“The endocannabinoid system (ECS) is a group of neuromodulatory lipids and their receptors, which are widely distributed in mammalian tissues. ECS regulates various cardiovascular, nervous, and immune system functions inside cells.

In recent years, there has been a growing body of evidence for the use of synthetic and natural cannabinoids as potential anticancer agents.

For instance, the CB1 and CB2 receptors are assumed to play an important role inside the endocannabinoid system. These receptors are abundantly expressed in the brain and fatty tissue of the human body.

Despite recent developments in molecular biology, there is still a lack of knowledge about the distribution of CB1 and CB2 receptors in the human kidney and their role in kidney cancer. To address this gap, we explore and demonstrate the role of the endocannabinoid system in renal cell carcinoma (RCC).

In this brief overview, we elucidate the therapeutic aspects of the endocannabinoid system for various cancers and explain how this system can be used for treating kidney cancer.

Overall, this review provides new insights into cannabinoids’ mechanisms of action in both in vivo and in vitro models, and focuses on recent discoveries in the field.”

http://www.ncbi.nlm.nih.gov/pubmed/26654588

Potentiation of the antitumor activity of adriamycin against osteosarcoma by cannabinoid WIN-55,212-2

Posted on December 3, 2015 by David

“Osteosarcoma is the most frequent primary malignant bone tumor that occurs in children and adolescents. Osteosarcoma is a bone malignancy that predominantly affects children and adolescents, and exhibits high invasion and metastasis rates.

Although adriamycin (ADM) is an effective benchmark agent for the management of osteosarcoma, it also results in harmful side-effects including toxicity and chemoresistance that substantially affect the quality of life of patients. Therefore, novel therapeutic approaches and drugs must be sought for the treatment of osteosarcoma.

Natural products which have potential antitumor activities have become a focus of attention for study in previous years. Cannabinoids, the active components naturally derived from the marijuana plant Cannabis sativa L., have been reported as potential antitumor drugs based on their ability to limit inflammation, cell proliferation and cell survival.

To date, several cannabinoids have been identified and characterized, including Δ(9)-tetrahydrocannabinol (THC), cannabidiol, cannabinol (CBN) and anandamide, as well as synthetic cannabinoids, including WIN-55,212-2, JWH-133 and (R)-methanandamide.

In the early 1970s, THC and CBN were shown to inhibit tumor growth in Lewis lung carcinoma. Subsequently, cannabinoids were found to induce apoptosis and inhibit the proliferation of various cancer cells, including those of glioma and lymphoma, and prostate, breast, skin and pancreatic cancer…

In conclusion, the present study indicated that cannabinoid WIN-55,212-2 is antiproliferative, antimetastatic and antiangiogenic against MG-63 cells in vitro, and presented evidence that cannabinoid WIN-55,212-2 may result in synergistic antitumor action in combination with ADM against osteosarcoma.

These findings may offer a novel strategy for the treatment of osteosarcoma.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4580018/

Controlled release tablet formulation containing natural δ9 tetrahydrocannabinol.

Posted on November 21, 2015 by David

“Cannabinoids are increasingly being used in the treatment of chemotherapy induced nausea and vomiting (CINV) because of their action on the cannabinoid receptors, CB1 and CB2.

The currently marketed capsule formulations (sesame oil based and crystalline powder) are required to be administered frequently to maintain therapeutic levels, which leads to non-compliance.

In the present study, oral controlled release tablet formulations of Δ9- tetrahydrocannabinol (THC) were prepared using the lipids Precirol® and Compritrol®. Release profiles using THC-lipid matrices and/or with the lipids in the external phase (blend) were evaluated…

The overall results demonstrate the feasibility of preparing oral THC tablets for once a day administration which can improve CINV management.”

http://www.ncbi.nlm.nih.gov/pubmed/26585693

Cannabinoids for nausea and vomiting in adults with cancer receiving chemotherapy.

Posted on November 13, 2015 by David

“Cannabis has a long history of medicinal use.

Cannabis-based medications (cannabinoids) are based on its active element, delta-9-tetrahydrocannabinol (THC), and have been approved for medical purposes.

Cannabinoids may be a useful therapeutic option for people with chemotherapy-induced nausea and vomiting that respond poorly to commonly used anti-emetic agents (anti-sickness drugs).

Cannabis-based medications may be useful for treating refractory chemotherapy-induced nausea and vomiting.”

http://www.ncbi.nlm.nih.gov/pubmed/26561338

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

Clinical Significance of Cannabinoid Receptors CB1 and CB2 Expression in Human Malignant and Benign Thyroid Lesions.

Posted on November 6, 2015 by David

“The endocannabinoid system is comprised of cannabinoid receptors (CB1 and CB2), their endogenous ligands (endocannabinoids), and proteins responsible for their metabolism participate in many different functions indispensable to homeostatic regulation in several tissues, exerting also antitumorigenic effects.

The present study aimed to evaluate the clinical significance of CB1 and CB2 expression in human benign and malignant thyroid lesions.

Our data suggest that CB receptors may be involved in malignant thyroid transformation and especially CB2 receptor could serve as useful biomarker and potential therapeutic target in thyroid neoplasia.”

http://www.ncbi.nlm.nih.gov/pubmed/26539529

http://www.hindawi.com/journals/bmri/2015/839403/

Cannabinoids and cancer: potential for colorectal cancer therapy.

Posted on October 23, 2015 by David

“Despite extensive research into the biology of CRC (colorectal cancer), and recent advances in surgical techniques and chemotherapy, CRC continues to be a major cause of death throughout the world. Therefore it is important to develop novel chemopreventive/chemotherapeutic agents for CRC.

Cannabinoids are a class of compounds that are currently used in the treatment of chemotherapy-induced nausea and vomiting, and in the stimulation of appetite. However, there is accumulating evidence that they could also be useful for the inhibition of tumour cell growth by modulating key survival signalling pathways.

The chemotherapeutic potential for plant-derived and endogenous cannabinoids in CRC therapy is reviewed.”

http://www.ncbi.nlm.nih.gov/pubmed/16042581

Plant derived substances with anti-cancer activity: from folklore to practice.

Posted on October 21, 2015 by David

“Plants have had an essential role in the folklore of ancient cultures. In addition to the use as food and spices, plants have also been utilized as medicines for over 5000 years.

It is estimated that 70-95% of the population in developing countries continues to use traditional medicines even today. A new trend, that involved the isolation of plant active compounds begun during the early nineteenth century.

This trend led to the discovery of different active compounds that are derived from plants.

In the last decades, more and more new materials derived from plants have been authorized and subscribed as medicines, including those with anti-cancer activity.

Cancer is among the leading causes of morbidity and mortality worldwide. The number of new cases is expected to rise by about 70% over the next two decades. Thus, there is a real need for new efficient anti-cancer drugs with reduced side effects, and plants are a promising source for such entities.

Here we focus on some plant-derived substances exhibiting anti-cancer and chemoprevention activity, their mode of action and bioavailability. These include paclitaxel, curcumin, and cannabinoids.

In addition, development and use of their synthetic analogs, and those of strigolactones, are discussed. Also discussed are commercial considerations and future prospects for development of plant derived substances with anti-cancer activity.”

http://www.ncbi.nlm.nih.gov/pubmed/26483815

http://journal.frontiersin.org/article/10.3389/fpls.2015.00799/full

Human lung-resident macrophages express CB1 and CB2 receptors whose activation inhibits the release of angiogenic and lymphangiogenic factors.

Posted on October 16, 2015 by David

“Macrophages are pivotal effector cells in immune responses and tissue remodeling by producing a wide spectrum of mediators, including angiogenic and lymphangiogenic factors.

Activation of cannabinoid receptor types 1 and 2 has been suggested as a new strategy to modulate angiogenesis in vitro and in vivo.

We investigated whether human lung-resident macrophages express a complete endocannabinoid system by assessing their production of endocannabinoids and expression of cannabinoid receptors…

Activation of cannabinoid receptors on tissue-resident macrophages might be a novel strategy to modulate macrophage-assisted vascular remodeling in cancer and chronic inflammation.”

http://www.ncbi.nlm.nih.gov/pubmed/26467187

Evaluation of cannabinoid CB1 and CB2 receptors expression in mobile tongue squamous cell carcinoma: associations with clinicopathological parameters and patients’ survival.

Posted on October 16, 2015 by David

Tumor Biology

“Cannabinoid receptors (CB1R and CB2R) constitute essential members of the endocannabinoid system (ECS) which participates in many different functions indispensable to homeostatic regulation in several tissues, exerting also antitumorigenic effects. The present study aimed to assess the clinical significance of CB1R and CB2R protein expression in mobile tongue squamous cell carcinoma (SCC). The present study provides evidence that CB1R and CB2R may play a role in the pathophysiological aspects of the mobile tongue SCC and even each molecule may constitute a potential target for the development of novel anti-cancer drugs for this type of malignancy.” http://www.ncbi.nlm.nih.gov/pubmed/26459312

https://link.springer.com/article/10.1007%2Fs13277-015-4182-8

Endocannabinoids and Cancer.

Posted on September 27, 2015 by David

“A large body of evidence shows that cannabinoids, in addition to their well-known palliative effects on some cancer-associated symptoms, can reduce tumour growth in animal models of cancer.

They do so by modulating key cell signalling pathways involved in the control of cancer cell proliferation and survival.

In addition, cannabinoids inhibit angiogenesis and cell proliferation in different types of tumours in laboratory animals.

By contrast, little is known about the biological role of the endocannabinoid system in cancer physio-pathology, and several studies suggest that it may be over-activated in cancer.

In this review, we discuss our current understanding of cannabinoids as antitumour agents, focusing on recent advances in the molecular mechanisms of action, including resistance mechanisms and opportunities for combination therapy approaches.”

http://www.ncbi.nlm.nih.gov/pubmed/26408171

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