Category Archives: Rhabdomyosarcoma

Use of cannabinoid receptor agonists in cancer therapy as palliative and curative agents.

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“Cannabinoids (the active components of Cannabis sativa) and their derivatives have received renewed interest in recent years due to their diverse pharmacological activities. In particular, cannabinoids offer potential applications as anti-tumour drugs, based on the ability of some members of this class of compounds to limit cell proliferation and to induce tumour-selective cell death. Although synthetic cannabinoids may have pro-tumour effects in vivo due to their immunosuppressive properties, predominantly inhibitory effects on tumour growth and migration, angiogenesis, metastasis, and also inflammation have been described. Emerging evidence suggests that agonists of cannabinoid receptors expressed by tumour cells may offer a novel strategy to treat cancer. In this chapter we review the more recent results generating interest in the field of cannabinoids and cancer, and provide novel suggestions for the development, exploration and use of cannabinoid agonists for cancer therapy, not only as palliative but also as curative drugs.” https://www.ncbi.nlm.nih.gov/pubmed/19285265

“Use of cannabinoid receptor agonists in cancer therapy as palliative and curative agents” http://www.bprcem.com/article/S1521-690X(09)00005-0/abstract

Cannabinoid receptor ligands as potential anticancer agents–high hopes for new therapies?

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“OBJECTIVES:

The endocannabinoid system is an endogenous lipid signalling network comprising arachidonic-acid-derived ligands, cannabinoid (CB) receptors, transporters and endocannabinoid degrading enzymes. The CB(1) receptor is predominantly expressed in neurons but is also co-expressed with the CB(2) receptor in peripheral tissues. In recent years, CB receptor ligands, including Delta(9)-tetrahydrocannabinol, have been proposed as potential anticancer agents.

KEY FINDINGS:

This review critically discusses the pharmacology of CB receptor activation as a novel therapeutic anticancer strategy in terms of ligand selectivity, tissue specificity and potency. Intriguingly, antitumour effects mediated by cannabinoids are not confined to inhibition of cancer cell proliferation; cannabinoids also reduce angiogenesis, cell migration and metastasis, inhibit carcinogenesis and attenuate inflammatory processes. In the last decade several new selective CB(1) and CB(2) receptor agents have been described, but most studies in the area of cancer research have used non-selective CB ligands. Moreover, many of these ligands exert prominent CB receptor-independent pharmacological effects, such as activation of the G-protein-coupled receptor GPR55, peroxisome proliferator-activated receptor gamma and the transient receptor potential vanilloid channels.

SUMMARY:

The role of the endocannabinoid system in tumourigenesis is still poorly understood and the molecular mechanisms of cannabinoid anticancer action need to be elucidated. The development of CB(2)-selective anticancer agents could be advantageous in light of the unwanted central effects exerted by CB(1) receptor ligands. Probably the most interesting question is whether cannabinoids could be useful in chemoprevention or in combination with established chemotherapeutic agents.”

http://www.ncbi.nlm.nih.gov/pubmed/19589225

[The endocannabinoid system as a target for the development of new drugs for cancer therapy].

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“Studies on the main bioactive components of Cannabis sativa, the cannabinoids, and particularly delta 9-tetrahydrocannabinol (THC), led to the discovery of a new endogenous signalling system that controls several physiological and pathological conditions: the endocannabinoid system. This comprises the cannabinoid receptors, their endogenous agonists–the endocannabinoids–and proteins for endocannabinoid biosynthesis and inactivation.

Recently, evidence has accumulated indicating that stimulation of cannabinoid receptors by either THC or the endocannabinoids influence the intracellular events controlling the proliferation and apoptosis of numerous types of cancer cells, thereby leading to anti-tumour effects both in vitro and in vivo.

This evidence is reviewed here and suggests that future anti-cancer therapy might be developed from our knowledge of how the endocannabinoid system controls the growth and metastasis of malignant cells.”

http://www.ncbi.nlm.nih.gov/pubmed/12723496

Endocannabinoid system modulation in cancer biology and therapy.

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“The discovery of the endocannabinoid system and the recognition of its potential impact in a plethora of pathological conditions, led to the development of therapeutic agents related to either the stimulation or antagonism of CB1 and CB2 cannabinoid receptors, the majority of which are actually tested in preclinical studies for the pharmacotherapy of several diseases. Endocannabinoid-related agents have been reported to affect multiple signaling pathways and biological processes involved in the development of cancer, displaying an interesting anti-proliferative, pro-apoptotic, anti-angiogenic and anti-metastatic activity both in vitro and in vivo in several models of cancer. Emerging evidence suggests that agonists of cannabinoid receptors, which share the useful property to discern between tumor cells and their non-transformed counterparts, could represent novel tumor-selective tools to treat cancer in addition to their already exploited use as palliative drugs to treat chemotherapy-induced nausea, pain and anorexia/weight loss in cancer patients. The aim of this review is to evidence and update the recent emerging knowledge about the role of the endocannabinoid system in cancer biology and the potentiality of its modulation in cancer therapy.”  http://www.ncbi.nlm.nih.gov/pubmed/19559362

http://www.sciencedirect.com/science/article/pii/S1043661809000863

Changes in the Endocannabinoid System May Give Insight into new and Effective Treatments for Cancer

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“The endocannabinoid system comprises specific cannabinoid receptors such as Cb1 and Cb2, the endogenous ligands (anandamide and 2-arachidonyl glycerol among others) and the proteins responsible for their synthesis and degradation. This system has become the focus of research in recent years because of its potential therapeutic value several disease states. The following review describes our current knowledge of the changes that occur in the endocannabinoid system during carcinogenesis and then focuses on the effects of anandamide on various aspects of the carcinogenic process such as growth, migration, and angiogenesis in tumors from various origins.

Marijuana and its derivatives have been used in medicine for centuries, however, it was not until the isolation of the psychoactive component of Cannabis sativa (Δ9-tetrahydrocannabinol; Δ9-THC) and the subsequent discovery of the endogenous cannabinoid signaling system that research into the therapeutic value of this system reemerged. Ongoing research is determining that regulation of the endocannabinoid system may be effective in the treatment of pain (Calignano et al., 1998; Manzanares et al., 1999), glaucoma (Voth and Schwartz, 1997), and neurodegenerative disorders such as Parkinson’s disease (Piomelli et al., 2000) and multiple sclerosis (Baker et al., 2000). In addition, cannabinoids might be effective anti-tumoral agents because of their ability to inhibit the growth of various types of cancer cell lines in culture (De Petrocellis et al., 1998; Ruiz et al., 1999; Sanchez et al., 1998, 2001) and in laboratory animals (Galve-Roperh et al., 2000).

In conclusion, the endocannabinoid system exerts a myriad of effects on tumor cell growth, progression, angiogenesis, and migration. With a notable few exceptions, targeting the endocannabinoid system with agents that activate cannabinoid receptors or increase the endogenous levels of AEA may prove to have therapeutic benefit in the treatment of various cancers. Further studies into the downstream consequences of AEA treatment are required and may illuminate other potential therapeutic targets.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2791688/

Receptor-dependent and Receptor-independent Endocannabinoid Signaling: A Therapeutic Target for Regulation of Cancer Growth.

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“The endocannabinoid system comprises the G-protein coupled CB1 cannabinoid receptor (CB1R) and CB2 cannabinoid receptor (CB2R), their endogenous ligands (endocannabinoids), and the enzymes responsible for their synthesis and catabolism. Recent works have revealed several important interactions between the endocannabinoid system and cancer. Moreover, it is now well established that synthetic small molecule cannabinoid receptor agonist acting on either CB1R or CB2R or both exert anti-cancer effects on a variety of tumor cells. Recent results from many laboratories reported that the expression of CB1R and CB2R in prostate cancer, breast cancer, and many other cancer cells are higher than corresponding non-malignant tissues. The mechanisms by which cannabinoids acting on CB1R or CB2R exert their effects on cancer cells are quite diverse and complex. Further, several studies demonstrated that some of the anti-proliferative and apoptotic effects of cannabinoids are mediated by receptor-independent mechanisms. In this minreview we provide an overview of the major findings on the effects of endogenous and/or synthetic cannabinoids on breast and prostate cancer. We also provide insight into receptor independent mechanisms of the anti-cancer effects of cannabinoids under in vitro and in vivo conditions.” http://www.ncbi.nlm.nih.gov/pubmed/23069587

http://www.sciencedirect.com/science/article/pii/S0024320512005930

Targeting the endocannabinoid system for the treatment of cancer– a practical view.

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“In recent years, considerable interest has been generated by findings that cannabinoids not only have useful palliative effects, but also can affect the viability and invasivity of a variety of different cancer cells. In the present review, the potential of targeting the cannabinoid system for the treatment of cancer is considered from a practical, rather than a mechanistic viewpoint, addressing questions such as whether human tumour cells express CB receptors; whether the potencies of action of cannabinoids in vitro match the potencies expected on the base of receptor theory; what is known about the in vivo effects of cannabinoids and cancer, and how relevant the experiments undertaken are to the clinical situation; and finally, what approaches can be taken to minimise unwanted effects of cannabinoid treatment. It is concluded that cannabinoids (or agents modulating the endogenous cannabinoid system) are an attractive target for drug development in the cancer area, but that more in vivo studies, particularly those investigating the potential of cannabinoids as an addition to current treatment strategies, are needed.”  http://www.ncbi.nlm.nih.gov/pubmed/20370711

http://www.eurekaselect.com/85470/article

Cannabinoids, Endocannabinoids and Cancer

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“The endocannabinoid system consists of an array of endogenously produced bioactive lipids that activate cannabinoid receptors. Although the primary focus of endocannabinoid biology has been on neurological and psychiatric effects, recent work has revealed several important interactions between the endocannabinoid system and cancer. Several different types of cancer have abnormal regulation of the endocannabinoid system that contributes to cancer progression and correlates to clinical outcomes.

Modulation of the endocannabinoid system by pharmacological agents in various cancer types reveals that it can mediate antiproliferative and apoptotic effects by both cannabinoid receptor-dependent and -independent pathways. Selective agonists and antagonists of the cannabinoid receptors, inhibitors of endocannabinoid hydrolysis, and cannabinoid analogs have been utilized to probe the pathways involved in the effects of the endocannabinoid system on cancer cell apoptosis, proliferation, migration, adhesion, and invasion. The antiproliferative and apoptotic effects produced by some of these pharmacological probes reveal that the endocannabinoid system is a promising new target for the development of novel chemotherapeutics to treat cancer.”

Although there is a strong set of data in vitro, in cellular model systems, and in mouse model systems, there is a dearth of clinical data on the effects of cannabinoids in the treatment of cancer in humans. This fact is quite surprising considering the large library of compounds that have been developed and used to study the effects of cannabinoids on cancer in model systems.

Despite the lack of preclinical and clinical data, there is a strong agreement that pharmacological targeting of the endocannabinoid system is emerging as one of the most promising new methods for reducing the progression of cancer. In particular, combination therapy utilizing both traditional chemotherapeutics and molecules targeting the endocannabinoid system may be an excellent next generation treatment for cancer.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3366283/

The endocannabinoid system in cancer-potential therapeutic target?

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“Endogenous arachidonic acid metabolites with properties similar to compounds of Cannabis sativa Linnaeus, the so-called endocannabinoids, have effects on various types of cancer. Although endocannabinoids and synthetic cannabinoids may have pro-proliferative effects, predominantly inhibitory effects on tumor growth, angiogenesis, migration and metastasis have been described. Remarkably, these effects may be selective for the cancer cells, while normal cells and tissues are spared. Such apparent tumor cell selectivity makes the endocannabinoid system an attractive potential target for cancer therapy. In this review we discuss various means by which the endocannabinoid system may be targeted in cancer and the current knowledge considering the regulation of the endocannabinoid system in malignancy.”  http://www.ncbi.nlm.nih.gov/pubmed/18249558

http://www.sciencedirect.com/science/article/pii/S1044579X07001058

Endocannabinoids as emerging suppressors of angiogenesis and tumor invasion (review).

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“The medicinal properties of extracts from the hemp plant Cannabis sativa have been known for centuries but only in the 90s membrane receptors for the Cannabis major principle were discovered in mammalian cells. Later on the endogenous ligands for the cannabinoid receptors were identified and the term ‘endocannabinoid system’ was coined to indicate the complex signaling system of cannabinoid receptors, endogenous ligands and the enzymes responsible for their biosynthesis and inactivation.

The ‘endocannabinoid system’ is involved in a broad range of functions and in a growing number of pathological conditions.

There is increasing evidence that endocannabinoids are able to inhibit cancer cell growth in culture as well as in animal models.

Most work has focused on the role of endocannabinoids in regulating tumor cell growth and apoptosis and ongoing research is addressed to further dissect the precise mechanisms of cannabinoid antitumor action. However, endocannabinoids are now emerging as suppressors of angiogenesis and tumor spreading since they have been reported to inhibit angiogenesis, cell migration and metastasis in different types of cancer, pointing to a potential role of the endocannabinoid system as a target for a therapeutic approach of such malignant diseases.

The potential use of cannabinoids to retard tumor growth and spreading is even more appealing considering that they show a good safety profile, regarding toxicity, and are already used in cancer patients as palliatives to stimulate appetite and to prevent devastating effects such as nausea, vomiting and pain.”  http://www.ncbi.nlm.nih.gov/pubmed/17342320

https://www.spandidos-publications.com/or/17/4/813