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      The Therapeutic Aspects of the Endocannabinoid System (ECS) for Cancer and their Development: From Nature to Laboratory

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          Abstract

          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 CB 1 and CB 2 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 CB 1 and CB 2 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.

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          Structure of a cannabinoid receptor and functional expression of the cloned cDNA.

          Marijuana and many of its constituent cannabinoids influence the central nervous system (CNS) in a complex and dose-dependent manner. Although CNS depression and analgesia are well documented effects of the cannabinoids, the mechanisms responsible for these and other cannabinoid-induced effects are not so far known. The hydrophobic nature of these substances has suggested that cannabinoids resemble anaesthetic agents in their action, that is, they nonspecifically disrupt cellular membranes. Recent evidence, however, has supported a mechanism involving a G protein-coupled receptor found in brain and neural cell lines, and which inhibits adenylate cyclase activity in a dose-dependent, stereoselective and pertussis toxin-sensitive manner. Also, the receptor is more responsive to psychoactive cannabinoids than to non-psychoactive cannabinoids. Here we report the cloning and expression of a complementary DNA that encodes a G protein-coupled receptor with all of these properties. Its messenger RNA is found in cell lines and regions of the brain that have cannabinoid receptors. These findings suggest that this protein is involved in cannabinoid-induced CNS effects (including alterations in mood and cognition) experienced by users of marijuana.
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            Chemical constituents of marijuana: the complex mixture of natural cannabinoids.

            The cannabis plant (Cannabis sativa L.) and products thereof (such as marijuana, hashish and hash oil) have a long history of use both as a medicinal agent and intoxicant. Over the last few years there have been an active debate regarding the medicinal aspects of cannabis. Currently cannabis products are classified as Schedule I drugs under the Drug Enforcement Administration (DEA) Controlled Substances act, which means that the drug is only available for human use as an investigational drug. In addition to the social aspects of the use of the drug and its abuse potential, the issue of approving it as a medicine is further complicated by the complexity of the chemical make up of the plant. This manuscript discusses the chemical constituents of the plant with particular emphasis on the cannabinoids as the class of compounds responsible for the drug's psychological properties.
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              Tumour microenvironment - opinion: validating matrix metalloproteinases as drug targets and anti-targets for cancer therapy.

              The matrix metalloproteinases (MMPs) mediate homeostasis of the extracellular environment. They have multiple signalling activities that are commonly altered during tumorigenesis and that might serve as intervention points for anticancer drugs. However, there are many criteria to consider in validating MMPs as drug targets and for the development of MMP inhibitors. The inhibition of some MMPs could have pro-tumorigenic effects (making them anti-targets), counterbalancing the benefits of target inhibition. These effects might partially account for the failure of MMP inhibitors in clinical trials. What are the major challenges in MMP target validation and MMP-inhibitor-drug development?
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                Author and article information

                Journal
                Curr Pharm Des
                Curr. Pharm. Des
                CPD
                Current Pharmaceutical Design
                Bentham Science Publishers
                1381-6128
                1873-4286
                March 2016
                March 2016
                : 22
                : 12
                : 1756-1766
                Affiliations
                [1 ]Molecular Oncology Laboratory, Department of Oncology, Military Institute of Medicine, ul. Szaserów 128, 04-141 Warsaw, Poland;
                [2 ]Department of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences - WULS, Warsaw, Poland;
                [3 ]Dipartimento di Chimica e Tecnologie del Farmaco, Università degli Studi di Roma “La Sapienza,” Piazzale Aldo Moro 5, 00185 Roma, Italy
                Author notes
                [* ]Address correspondence to this author at the Molecular Oncology Laboratory, Department of Oncology, Military Institute of Medicine, ul. Szaserów 128, 04-141 Warsaw, Poland; Tel: +48-790763164; Fax: +48-22-610-30-98; E-mails: mkhan@ 123456wim.mil.pl ; imrankhanbioinfo@ 123456gmail.com
                Article
                CPD-22-1756
                10.2174/1381612822666151211094901
                5412000
                26654588
                da9d0acd-851c-46bf-b6a6-92348dcb2098
                © 2016 Bentham Science Publishers

                This is an open access article licensed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International Public License (CC BY-NC 4.0) ( https://creativecommons.org/licenses/by-nc/4.0/legalcode), which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

                History
                : 30 October 2015
                : 10 December 2015
                Categories
                Article

                Pharmacology & Pharmaceutical medicine
                cb1 and cb2 receptors,cannabinoids,endocannabinoid system,renal cell carcinoma

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