Posted: 24th April 2019

Subject: IM Approaches by Illness, Gender & Age / Sub-category: Bowel Cancer

Cannabis Research for Colon Cancer

Article source: https://www.sativaisticated.com/medical-cannabis/research/cannabis-research-for-colon-cancer/

Accessed from the world wide web at 11:00 hrs on 04.04.19.

Colon cancer is a disease in which malignant (cancer) cells form in the tissues of the colon.

The colon is part of the body’s digestive system. The digestive system removes and processes nutrients (vitamins, minerals, carbohydrates, fats, proteins, and water) from foods and helps pass waste material out of the body. The digestive system is made up of the esophagus, stomach, and the small and large intestines. The colon (large bowel) is the first part of the large intestine and is about 5 feet long. Together, the rectum and anal canal make up the last part of the large intestine and are about 6-8 inches long. The anal canal ends at the anus (the opening of the large intestine to the outside of the body).

Gastrointestinal stromal tumors can occur in the colon. — National Cancer Institute

Below is a Library of Cannabis Research Studies for Colon Cancer.

Can Cannabidiol Inhibit Angiogenesis in Colon Cancer?

Comparative Clinical Pathology | August 2018
Abstract: “Colon cancer is the third most common human malignancy and a main cause of death worldwide. The current study was carried out to investigate the effects of cannabidiol, a cannabinoid, on angiogenesis and cell death in mice with experimental colon cancer induced by injection of CT26 cell line. Fifty male BALB/c mice were assigned randomly to five study groups, including: (1) negative control, (2) cancer control, (3) cancer vehicle control, (3) cancer treatment (1 mg/kg cannabidiol), and (5) cancer treatment (5 mg/kg cannabidiol). Treatment responses were evaluated based on histopathological examination, the expression of vascular endothelial growth factor (VEGF) gene, measurement of interleukins (ILs 6 and 8), oxidative stress parameters (glutathione peroxidase, glutathione reductase, superoxide dismutase serum activities, total antioxidant capacity, and malondialdehyde levels). In the present study, CBD reduced VEGF gene expression, decreased serum levels of IL6, IL8, and malondialdehyde, and increased antioxidant enzyme activity in mice with colon cancer. Moreover, cannabidiol induced apoptosis and reduced cellular pleomorphism. Cannabidiol can be potentially considered as an anti-colon cancer medicine as it exerts an inhibitory effect on angiogenesis, tumor growth, and metastasis through reducing VEGF gene expression, decreasing cytokines, and increasing antioxidant enzyme activities.” — Study

Cannabinoid Pharmacology and Therapy in Gut Disorders

Biochemical Pharmacology | August 2018
Abstract: “Cannabis sp and their products (marijuana, hashish…), in addition to their recreational, industrial and other uses, have a long history for their use as a remedy for symptoms related with gastrointestinal diseases. After many reports suggesting these beneficial effects, it was not surprising to discover that the gastrointestinal tract expresses endogenous cannabinoids, their receptors, and enzymes for their synthesis and degradation, comprising the so-called endocannabinoid system. This system participates in the control of tissue homeostasis and important intestinal functions like motor and sensory activity, nausea, emesis, the maintenance of the epithelial barrier integrity, and the correct cellular microenvironment. Thus, different cannabinoid-related pharmacological agents may be useful to treat the main digestive pathologies. To name a few examples, in irritable bowel syndrome they may normalize dysmotility and reduce pain, in inflammatory bowel disease they may decrease inflammation, and in colorectal cancer, apart from alleviating some symptoms, they may play a role in the regulation of the cell niche.

This review summarizes the main recent findings on the role of cannabinoid receptors, their synthetic or natural ligands and their metabolizing enzymes in normal gastrointestinal function and in disorders including irritable bowel syndrome, inflammatory bowel disease, colon cancer and gastrointestinal chemotherapy-induced adverse effects (nausea/vomiting, constipation, diarrhea).” — Study

Identification of Synergistic Interaction Between Cannabis-Derived Compounds for Cytotoxic Activity in Colorectal Cancer Cell Lines and Colon Polyps That Induces Apoptosis-Related Cell Death and Distinct Gene Expression

Cannabis and Cannabinoid ResearchVol. 3, No. 1 | June 2018
Abstract: “Colorectal cancer remains the third most common cancer diagnosis and fourth leading cause of cancer-related mortality worldwide. Purified cannabinoids have been reported to prevent proliferation, metastasis, and induce apoptosis in a variety of cancer cell types. However, the active compounds from Cannabis sativa flowers and their interactions remain elusive…This study was aimed to specify the cytotoxic effect of C. sativa-derived extracts on colon cancer cells and adenomatous polyps by identification of active compound(s) and characterization of their interaction…Ethanol extracts of C. sativa were analyzed by high-performance liquid chromatography and gas chromatograph/mass spectrometry and their cytotoxic activity was determined using alamarBlue-based assay (Resazurin) and tetrazolium dye-based assay (XTT) on cancer and normal colon cell lines and on dysplastic adenomatous polyp cells. Annexin V Assay and fluorescence-activated cell sorting (FACS) were used to determine apoptosis and cell cycle, and RNA sequencing was used to determine gene expression…The unheated cannabis extracts (C2F), fraction 7 (F7), and fraction 3 (F3) had cytotoxic activity on colon cancer cells, but reduced activity on normal colon cell lines. Moreover, synergistic interaction was found between F7 and F3 and the latter contains mainly cannabigerolic acid. The F7 and F7+F3 cytotoxic activity involved cell apoptosis and cell cycle arrest in S or G0/G1 phases, respectively. RNA profiling identified 2283 differentially expressed genes in F7+F3 treatment, among them genes related to the Wnt signaling pathway and apoptosis-related genes. Moreover, F7, F3, and F7+F3 treatments induced cell death of polyp cells…C. sativa compounds interact synergistically for cytotoxic activity against colon cancer cells and induce cell cycle arrest, apoptotic cell death, and distinct gene expression. F3, F7, and F7+F3 are also active on adenomatous polyps, suggesting possible future therapeutic value.” — Study

Medical Cannabis and Cannabinoids: An Option for the Treatment of Inflammatory Bowel Disease and Cancer of the Colon?

Medical Cannabis and Cannabinoids | June 2018
Abstract: “In the past few years, we have witnessed a surge of new reports dealing with the role of cannabinoids, synthetic as well as herbal, in the mechanisms of inflammation and carcinogenesis. However, despite the wealth of in vitro data and anecdotal reports, evidence that cannabinoids could act as beneficial drugs in inflammatory bowel disease (IBD) or in neoplastic development of the human gastrointestinal tract is lacking. Some insight into the effects of medical Cannabis (usually meaning dried flowers) and cannabinoids in IBD has been gained through questionnaires and small pilot studies. As to colorectal cancer, only preclinical data are available. Currently, Δ9-tetrahydrocannabinol (THC) and its synthetic forms, dronabinol and nabilone, are used as an add-on treatment to alleviate chronic pain and spasticity in multiple sclerosis patients as well as chemotherapy-induced nausea. The use of medical Cannabis is authorized only in a limited number of countries. None of the mentioned substances are currently indicated for IBD. This review is an update of our knowledge on the role of cannabinoids in intestinal inflammation and carcinogenesis and a discussion on their potential therapeutic use.” — Study

Prospective Analysis of Safety and Efficacy of Medical Cannabis in Large Unselected Population of Patients with Cancer

European Journal of Internal Medicine | January 2018
Abstract: “Cancer is a major public health problem as the leading cause of death. Palliative treatment aimed to alleviate pain and nausea in patients with advanced disease is a cornerstone of oncology. In 2007, the Israeli Ministry of Health began providing approvals for medical cannabis for the palliation of cancer symptoms. The aim of this study is to characterize the epidemiology of cancer patients receiving medical cannabis treatment and describe the safety and efficacy of this therapy…We analyzed the data routinely collected as part of the treatment program of 2970 cancer patients treated with medical cannabis between 2015 and 2017…The average age was 59.5 ± 16.3 years, 54.6% women and 26.7% of the patients reported previous experience with cannabis. The most frequent types of cancer were: breast (20.7%), lung (13.6%), pancreatic (8.1%) and colorectal (7.9%) with 51.2% being at stage 4. The main symptoms requiring therapy were: sleep problems (78.4%), pain (77.7%, median intensity 8/10), weakness (72.7%), nausea (64.6%) and lack of appetite (48.9%). After six months of follow up, 902 patients (24.9%) died and 682 (18.8%) stopped the treatment. Of the remaining, 1211 (60.6%) responded; 95.9% reported an improvement in their condition, 45 patients (3.7%) reported no change and four patients (0.3%) reported deterioration in their medical condition…Cannabis as a palliative treatment for cancer patients seems to be well tolerated, effective and safe option to help patients cope with the malignancy related symptoms.” — Study

GPCRs: Emerging Anti-Cancer Drug Targets

Cellular Signalling | September 2017
Abstract: “G protein-coupled receptors (GPCRs) constitute the largest and most diverse protein family in the human genome with over 800 members identified to date. They play critical roles in numerous cellular and physiological processes, including cell proliferation, differentiation, neurotransmission, development and apoptosis. Consequently, aberrant receptor activity has been demonstrated in numerous disorders/diseases, and as a result GPCRs have become the most successful drug target class in pharmaceuticals treating a wide variety of indications such as pain, inflammation, neurobiological and metabolic disorders. Many independent studies have also demonstrated a key role for GPCRs in tumourigenesis, establishing their involvement in cancer initiation, progression, and metastasis. Given the growing appreciation of the role(s) that GPCRs play in cancer pathogenesis, it is surprising to note that very few GPCRs have been effectively exploited in pursuit of anti-cancer therapies. The present review provides a broad overview of the roles that various GPCRs play in cancer growth and development, highlighting the potential of pharmacologically modulating these receptors for the development of novel anti-cancer therapeutics.” — Study

Cannabinoids as Anticancer Drugs

Advances in Pharmacology | June 2017
Abstract: “The endocannabinoid system encompassing cannabinoid receptors, endogenous receptor ligands (endocannabinoids), as well as enzymes conferring the synthesis and degradation of endocannabinoids has emerged as a considerable target for pharmacotherapeutical approaches of numerous diseases. Besides palliative effects of cannabinoids used in cancer treatment, phytocannabinoids, synthetic agonists, as well as substances that increase endogenous endocannabinoid levels have gained interest as potential agents for systemic cancer treatment. Accordingly, cannabinoid compounds have been reported to inhibit tumor growth and spreading in numerous rodent models. The underlying mechanisms include induction of apoptosis, autophagy, and cell cycle arrest in tumor cells as well as inhibition of tumor cell invasion and angiogenic features of endothelial cells. In addition, cannabinoids have been shown to suppress epithelial-to-mesenchymal transition, to enhance tumor immune surveillance, and to support chemotherapeutics’ effects on drug-resistant cancer cells. However, unwanted side effects include psychoactivity and possibly pathogenic effects on liver health. Other cannabinoids such as the nonpsychoactive cannabidiol exert a comparatively good safety profile while exhibiting considerable anticancer properties. So far experience with anticarcinogenic effects of cannabinoids is confined to in vitro studies and animal models. Although a bench-to-bedside conversion remains to be established, the current knowledge suggests cannabinoid compounds to serve as a group of drugs that may offer significant advantages for patients suffering from cancer diseases. The present review summarizes the role of the endocannabinoid system and cannabinoid compounds in tumor progression.” — Study

Cannabinoids as Modulators of Cell Death: Clinical Applications and Future Directions

Reviews of Physiology, Biochemistry and Pharmacology | April 2017
Abstract: “Endocannabinoids are bioactive lipids that modulate various physiological processes through G-protein-coupled receptors (CB1 and CB2) and other putative targets. By sharing the activation of the same receptors, some phytocannabinoids and a multitude of synthetic cannabinoids mimic the effects of endocannabinoids. In recent years, a growing interest has been dedicated to the study of cannabinoids properties for their analgesic, antioxidant, anti-inflammatory and neuroprotective effects. In addition to these well-recognized effects, various studies suggest that cannabinoids may affect cell survival, cell proliferation or cell death. These observations indicate that cannabinoids may play an important role in the regulation of cellular homeostasis and, thus, may contribute to tissue remodelling and cancer treatment. For a long time, the study of cannabinoid receptor signalling has been focused on the classical adenylyl cyclase/cyclic AMP/protein kinase A (PKA) pathway. However, this pathway does not totally explain the wide array of biological responses to cannabinoids. In addition, the diversity of receptors and signalling pathways that endocannabinoids modulate offers an interesting opportunity for the development of specific molecules to disturb selectively the endogenous system. Moreover, emerging evidences suggest that cannabinoids ability to limit cell proliferation and to induce tumour-selective cell death may offer a novel strategy in cancer treatment. This review describes the main properties of cannabinoids in cell death and attempts to clarify the different pathways triggered by these compounds that may help to understand the complexity of respective molecular mechanisms and explore the potential clinical benefit of cannabinoids use in cancer therapies.” — Review

Promises and Pitfalls of Cannabinoids as Agents with Potential Anticancer Efficacy

Journal of Neurology & Neuromedicine | September 2016
Abstract: “The endocannabinoid system is extensively studied in neuroscience and clinical use of cannabinoid derivatives as substances with remarkable spasmolytic effects in multiple sclerosis and antiemetic potential in cancer therapy as well as pain-relieving properties is broadly acknowledged. However, it becomes increasingly apparent, that in addition cannabinoids exert manifold functions in various organ systems, such as the immune system, the reproductive or cardiovascular system among others. Moreover, interactions with signaling pathways involved in programmed cell death, angiogenesis, metastasis or anti-tumor immunity make it highly suggestive that cannabinoids may have therapeutic potential in the treatment of cancer. Indeed, detailed reports have repeatedly shown an cancer efficacy in solid and hematologic tumor models, best characterized in human gliomas. Anecdotal evidence of blast control in a young patient with acute myeloid leukemia has led us to systematically investigate the potential use of cannabinoids in the treatment of acute leukemia. These data are summarized herein in the context of key data regarding an cancer efficacy of cannabinoids.” — Review

The Therapeutic Aspects Of The Endocannabinoid System (ECS) For Cancer And Their Development: From Nature To Laboratory.

Current Pharmaceutical Design | 2016
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 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.” — Study

Cannabinoids as Therapeutic Agents in Cancer: Current Status and Future Implications

Oncotarget | July 2014
Abstract: “The pharmacological importance of cannabinoids has been in study for several years. Cannabinoids comprise of (a) the active compounds of the Cannabis sativa plant, (b) endogenous as well as (c) synthetic cannabinoids. Though 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. Cannabinoids regulate key cell signaling pathways that are involved in cell survival, invasion, angiogenesis, metastasis, etc. There is more focus on CB1 and CB2, the two cannabinoid receptors which are activated by most of the cannabinoids. In this review article, we will focus on a broad range of cannabinoids, their receptor dependent and receptor independent functional roles against various cancer types with respect to growth, metastasis, energy metabolism, immune environment, stemness and future perspectives in exploring new possible therapeutic opportunities.” — Study

GPR55 Promotes Migration And Adhesion Of Colon Cancer Cells Indicating A Role In Metastasis

British Journal of Pharmacology | September 2015
Abstract: “Tumour cell migration and adhesion constitute essential features of metastasis. G‐protein coupled receptor 55 (GPR55), a lysophospholipid receptor, has been shown to play an important role in carcinogenesis. Here, we investigated the involvement of GPR55 in migration and metastasis of colon cancer cells…HCT116 cells showed a significant decrease in adhesion to endothelial cells and in migration after blockade with CID16020046 or cannabidiol. The inhibitory effects of CID16020046 or cannabidiol were averted by GPR55 siRNA knock down in cancer cells. The integrity of endothelial cell monolayers was increased after pretreatment of HCT116 cells with the antagonists or after GPR55 siRNA knockdown while pretreatment with lysophosphatidylinositol (LPI), the endogenous ligand of GPR55, decreased integrity of the monolayers. LPI also induced migration in GPR55 overexpressing HCT116 cells that was blocked by GPR55 antagonists. In a mouse model of metastasis, the arrest of HCT116 cancer cells in the liver was reduced after treatment with CID16020046 or cannabidiol. Increased levels of LPI (18:0) were found in colon cancer patients when compared with healthy individuals…GPR55 is involved in the migratory behaviour of colon carcinoma cells and may serve as a pharmacological target for the prevention of metastasis.” — Study

The Anticancer, Antioxidant And Antimicrobial Properties Of The Sesquiterpene β-Caryophyllene From The Essential Oil Of Aquilaria Crassna

Molecules | 2015
Abstract: “The present study reports a bioassay-guided isolation of β-caryophyllene from the essential oil of Aquilaria crassna. The structure of β-caryophyllene was confirmed using FT-IR, NMR and MS. The antimicrobial effect of β-caryophyllene was examined using human pathogenic bacterial and fungal strains. Its anti-oxidant properties were evaluated by DPPH and FRAP scavenging assays. The cytotoxicity of β-caryophyllene was tested against seven human cancer cell lines. The corresponding selectivity index was determined by testing its cytotoxicity on normal cells. The effects of β-caryophyllene were studied on a series of in vitro antitumor-promoting assays using colon cancer cells. Results showed that β-caryophyllene demonstrated selective antibacterial activity against S. aureus (MIC 3 ± 1.0 µM) and more pronounced anti-fungal activity than kanamycin. β-Caryophyllene also displayed strong antioxidant effects. Additionally, β-caryophyllene exhibited selective anti-proliferative effects against colorectal cancer cells (IC50 19 µM). The results also showed that β-caryophyllene induces apoptosis via nuclear condensation and fragmentation pathways including disruption of mitochondrial membrane potential. Further, β-caryophyllene demonstrated potent inhibition against clonogenicity, migration, invasion and spheroid formation in colon cancer cells. These results prompt us to state that β-caryophyllene is the active principle responsible for the selective anticancer and antimicrobial activities of A. crassnia. β-Caryophyllene has great potential to be further developed as a promising chemotherapeutic agent against colorectal malignancies.”— Study

Composition And In Vitro Anticancer Activities Of The Leaf Essential Oil Of Neolitsea Variabillima From Taiwan

Natural Products Communication | April 2013 
Abstract: “This study investigated the chemical composition and in vitro anticancer activities of the essential oil isolated from the leaf of Neolitsea variabillima. The essential oil was isolated using hydrodistillation in a Clevenger-type apparatus, and characterized by GC-FID and GC-MS. Sixty-seven compounds were identified, representing 100% of the oil. The main components identified were trans-beta-ocimene (13.4%), alpha-cadinol (10.5%), terpinen-4-ol (9.3%), tau-cadinol (9.2%), beta-caryophyllene (8.8%), and sabinene (6.7%). The anticancer activities of oil were evaluated. The results showed that the oil exhibited cytotoxic activity against human oral, liver, lung, colon, melanoma, and leukemic cancer cells. The presence of beta-caryophyllene, tau-cadinol, and alpha-cadinol significantly contributed to the anticancer activities of N. variabillima leaf oil.” — Study

Chemopreventive Effect Of The Non-psychotropic Phytocannabinoid Cannabidiol On Experimental Colon Cancer.

Journal of Molecular Medicine | August 2012
Abstract: “Colon cancer affects millions of individuals in Western countries. Cannabidiol, a safe and non-psychotropic ingredient of Cannabis sativa, exerts pharmacological actions (antioxidant and intestinal antinflammatory) and mechanisms (inhibition of endocannabinoid enzymatic degradation) potentially beneficial for colon carcinogenesis. Thus, we investigated its possible chemopreventive effect in the model of colon cancer induced by azoxymethane (AOM) in mice. AOM treatment was associated with aberrant crypt foci (ACF, preneoplastic lesions), polyps, and tumour formation, up-regulation of phospho-Akt, iNOS and COX-2 and down-regulation of caspase-3. Cannabidiol-reduced ACF, polyps and tumours and counteracted AOM-induced phospho-Akt and caspase-3 changes. In colorectal carcinoma cell lines, cannabidiol protected DNA from oxidative damage, increased endocannabinoid levels and reduced cell proliferation in a CB1-, TRPV1- and PPARγ-antagonists sensitive manner. It is concluded that cannabidiol exerts chemopreventive effect in vivo and reduces cell proliferation through multiple mechanisms.” — Study

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

Biological & Pharmaceutical Bulletin | 2012
Abstract: “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 LYR-8, a novel hexahydrocannabinol analog, exerts anti-angiogenic and anti-tumor activity in human cancer xenografts. In the xenografted tumor tissues, LYR-8 significantly reduced the expression of hypoxia-inducible factor-1 alpha (HIF-1α), a transcription factor responsible for induction of angiogenesis-promoting factors, and its target genes, vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2). In HT-29 human colon cancer cells treated with a hypoxia-inducing agent (CoCl(2)), LYR-8 dose-dependently suppressed the induction of HIF-1α and subsequently its targets, VEGF and COX-2. In addition, highly elevated prostaglandin E(2) (PGE(2)) concentrations in CoCl(2)-treated HT-29 cells were also significantly suppressed by LYR-8. However, LYR-8 alone in the absence of CoCl(2) did not alter the basal expression of VEGF and COX-2, or PGE(2) production. Furthermore, LYR-8 effectively suppressed Akt signaling, which corresponded to the suppression of CoCl(2)-induced HIF-1α accumulation. Taken together, LYR-8 exerts anti-tumor effects through the inhibition of Akt and HIF-1α activation, and subsequently suppressing factors regulating tumor microenvironment, such as VEGF and COX-2. These results indicate a novel function of cannabinoid-like compound LYR-8 as an anti-tumor agent with a HIF-1α inhibitory activity.”— Study

Evaluation Of The Cyclooxygenase Inhibiting Effects Of Six Major Cannabinoids Isolated From Cannabis Sativa

Biological & Pharmaceutical Bulletin | May 2011 
 “Cyclooxygenase enzymes (COX-1 and COX-2) catalyse the production of prostaglandins from arachidonic acid. Prostaglandins are important mediators in the inflammatory process and their production can be reduced by COX-inhibitors. Endocannabinoids, endogenous analogues of the plant derived cannabinoids, occur normally in the human body. The Endocannabinoids are structurally similar to arachidonic acid and have been suggested to interfere with the inflammatory process. They have also been shown to inhibit cancer cell proliferation. Anti-inflammatory effects of cannabinoids and endocannabinoids have been observed, however the mode of action is not yet clarified. Anti-inflammatory activity (i.e., inhibition of COX-2) is proposed to play an important role in the development of colon cancer, which makes this subject interesting to study further. In the present work, the six cannabinoids tetrahydrocannabinol (Δ⁹-THC), tetrahydrocannabinolic acid (Δ⁹-THC-A), cannabidiol (CBD), cannabidiolic acid (CBDA), cannabigerol (CBG) and cannabigerolic acid (CBGA), isolated from Cannabis sativa, were evaluated for their effects on prostaglandin production. For this purpose an in vitro enzyme based COX-1/COX-2 inhibition assay and a cell based prostaglandin production radioimmunoassay were used. Cannabinoids inhibited cyclooxygenase enzyme activity with IC₅₀ values ranging from 1.7·10⁻³ to 2.0·10⁻⁴ M.”— Study

Loss Of Cannabinoid Receptor 1 Accelerates Intestinal Tumor Growth

Cancer Research | August 2008
Abstract: “Although endocannabinoid signaling is important for certain aspects of gastrointestinal homeostasis, the role of the cannabinoid receptors (CB) in colorectal cancer has not been defined. Here we show that CB1 expression was silenced in human colorectal cancer due to methylation of the CB1 pro- moter. Our genetic and pharmacologic studies reveal that loss or inhibition of CB1 accelerated intestinal adenoma growth in ApcMin/+ mice whereas activation of CB1 attenuated intes- tinal tumor growth by inducing cell death via down-regulation of the antiapoptotic factor survivin. This down-regulation of survivin by CB1 is mediated by a cyclic AMP–dependent protein kinase A signaling pathway. These results indicate that the endogenous cannabinoid system may represent a potential therapeutic target for prevention or treatment of colorectal cancer.” — Study

Potentiating Effect Of Beta-caryophyllene On Anticancer Activity Of Alpha-humulene, Isocaryophyllene And Paclitaxel

Journal of Pharmacy and Pharmacology | December 2007 Abstract: “β-caryophyllene is a sesquiterpene widely distributed in essential oils of various plants. Several biological activities are attributed to β-caryophyllene, such as anti-inflammatory, antibiotic, antioxidant, anticarcinogenic and local anaesthetic activities. In this work, the potentiating effect of β-caryophyllene on the anticancer activity of α-humulene, isocaryophyllene and paclitaxel against MCF-7, DLD-1 and L-929 human tumour cell lines was evaluated. A non-cytotoxic concentration of β-caryophyllene significantly increased the anticancer activity of α-humulene and isocaryophyllene on MCF-7 cells: α-humulene or isocaryophyllene alone (32 μg mL−1) inhibited cell growth by about 50% and 69%, respectively, compared with 75% and 90% when combined with 10 μg mL−1 β-caryophyllene. Moreover, β-caryophyllene potentiated the anticancer activity of paclitaxel on MCF-7, DLD-1 and L-929 cell lines. The highest potentiating effect was obtained in DLD-1 cells treated with paclitaxel combined with 10 μg mL−1 β-caryophyllene, which increased the paclitaxel activity about 10-fold. The intracellular accumulation of paclitaxel-oregon green was evaluated in combination with concentrations of β-caryophyllene ranging from 2.5 to 40 μg mL−1. β-Caryophyllene (10 μg mL−1) significantly increased the intracellular accumulation of paclitaxel-oregon green (about 64% over controls). Moreover, β-caryophyllene induced intracellular accumulation of calcein but not verapamil, an inhibitor of P-glycoprotein and multidrug resistance related protein transporters, suggesting that β-caryophyllene promotes drug accumulation by a different mechanism of action. These results suggest that β-caryophyllene facilitates the passage of paclitaxel through the membrane and thus potentiates its anticancer activity.” — Study

The Endogenous Cannabinoid, Anandamide, Induces Cell Death In Colorectal Carcinoma Cells: A Possible Role For Cyclooxygenase 2

Gut | December 2005
Abstract: “Cyclooxygenase 2 (COX-2) is upregulated in most colorectal cancers and is responsible for metabolism of the endogenous cannabinoid, anandamide, into prostaglandin- ethanolamides (PG-EAs). The aims of this study were to determine whether anandamide and PG-EAs induce cell death in colorectal carcinoma (CRC) cells, and whether high levels of COX-2 in CRC cells could be utilised for their specific targeting for cell death by anandamide…Anandamide inhibited the growth of CRC cell lines HT29 and HCA7/C29 (moderate and high COX-2 expressors, respectively) but had little effect on the very low COX-2 expressing CRC cell line, SW480. Induction of cell death in HT29 and HCA7/C29 cell lines was partially rescued by the COX-2 selective inhibitor NS398. Cell death induced by anandamide was neither apoptosis nor necrosis. Furthermore, inhibition of fatty acid amide hydrolase potentiated the non-apoptotic cell death, indicating that anandamide induced cell death was mediated via metabolism of anandamide by COX-2, rather than its degradation into arachidonic acid and ethanolamine. Interestingly, both PGE2-EA and PGD2-EA induced classical apoptosis…These findings suggest anandamide may be a useful chemopreventive/therapeutic agent for colorectal cancer as it targets cells that are high expressors of COX-2, and may also be used in the eradication of tumour cells that have become resistant to apoptosis.”— Study