Tag Archives: chemopreventive

Antitumor Cannabinoid Chemotypes: Structural Insights.

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Image result for frontiers in pharmacology“Cannabis has long been known to limit or prevent nausea and vomiting, lack of appetite, and pain. For this reason, cannabinoids have been successfully used in the treatment of some of the unwanted side effects caused by cancer chemotherapy.

Besides their palliative effects, research from the past two decades has demonstrated their promising potential as antitumor agents in a wide variety of tumors.

Cannabinoids of endogenous, phytogenic, and synthetic nature have been shown to impact the proliferation of cancer through the modulation of different proteins involved in the endocannabinoid system such as the G protein-coupled receptors CB1, CB2, and GRP55, the ionotropic receptor TRPV1, or the fatty acid amide hydrolase (FAAH).

In this article, we aim to structurally classify the antitumor cannabinoid chemotypes described so far according to their targets and types of cancer. In a drug discovery approach, their in silico pharmacokinetic profile has been evaluated in order to identify appropriate drug-like profiles, which should be taken into account for further progress toward the clinic.

This analysis may provide structural insights into the selection of specific cannabinoid scaffolds for the development of antitumor drugs for the treatment of particular types of cancer.” https://www.ncbi.nlm.nih.gov/pubmed/31214034

“The first report on the antitumor activity of phytocannabinoids was published over four decades ago. During these last years, significant research has been focused on the therapeutic potential of cannabinoids to manage palliative effects in cancer patients. Besides such palliative applications, some cannabinoids have shown anticancer properties. Since inflammation is a common risk factor for cancer, and some cannabinoids have shown anti-inflammatory properties, they could play a role in chemoprevention.” https://www.frontiersin.org/articles/10.3389/fphar.2019.00621/full
“Antitumor effects of THC.” http://www.ncbi.nlm.nih.gov/pubmed/11097557
“Antitumor effects of cannabidiol” http://www.ncbi.nlm.nih.gov/pubmed/14617682
“Anti-tumour actions of cannabinoids.” https://www.ncbi.nlm.nih.gov/pubmed/30019449
“Extensive preclinical research has demonstrated that cannabinoids, the active ingredients of Cannabis sativa, trigger antitumor responses in different models of cancer.” https://www.ncbi.nlm.nih.gov/pubmed/29940172

It’s Colorectal Cancer Awareness Month. Please Be Aware:

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“Prevention and Treatment of Colorectal Cancer by Natural Agents From Mother Nature. This review clearly demonstrates that various nutraceuticals provided by the Mother Nature have a huge potential for both prevention and treatment of Colorectal cancer (CRC). Since these agents can be administered chronically without any concern for safety and are highly affordable, their use has been the wave of the past and is likely to continue as the wave of the future.” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3693477/
“Inflammatory Diet Linked to Colon Cancer, Metabolic Risk” https://www.psychologytoday.com/blog/nourish/201410/inflammatory-diet-linked-colon-cancer-metabolic-risk
“Links between inflammation and colon cancer metastasis” https://www.sciencedaily.com/releases/2015/08/150825094923.htm
“Inflammation and colon cancer. The connection between inflammation and tumorigenesis is well-established. Inflammation is also likely to be involved with other forms of sporadic as well as heritable colon cancer.” https://www.ncbi.nlm.nih.gov/pubmed/20420949
“Cannabis-derived substances in cancer therapy–an emerging anti-inflammatory role for the cannabinoids. Chronic inflammation has been associated with neoplasia for sometime, and as a consequence, reducing inflammation as a way of impacting cancer presents a new role for these compounds. ” https://www.ncbi.nlm.nih.gov/pubmed/20925645
“Cannabinoids as gastrointestinal anti-inflammatory drugs.” https://www.ncbi.nlm.nih.gov/pubmed/28239924
“Colon Cancer Risk Linked To High-Fat Diet: How Eating More Fat Can Increase Intestinal Tumors” http://www.medicaldaily.com/colon-cancer-high-fat-diet-intestinal-tumors-376664
 
“Study: Red and Processed Meats Linked With Colon Cancer Risk” http://healthland.time.com/2011/05/27/study-red-and-processed-meats-linked-with-colon-cancer-risk/
 
“Eating hot dogs, ham and other processed meat can cause colorectal cancer, and eating red meat “probably” can cause cancer, the World Health Organization’s cancer agency reported” http://www.usatoday.com/story/news/nation/2015/10/26/experts-processed-meats-can-cause-cancer/74615390/
 
“Mediterranean Diet Reduces Risk of Colon Cancer”
 
 
“More evidence a veg diet might lower cancer risk” http://www.today.com/health/veggie-diet-lowers-colon-cancer-risk-t7671
 
 
 
“Omegas linked with colon cancer survival. A large, observational study has linked higher intake of omega-3s with a lower risk of dying from colon cancer.” http://www.newhope.com/breaking-news/omegas-linked-colon-cancer-survival
 
 “Study shows how high-fat diets increase colon cancer risk” http://news.temple.edu/news/2012-03-06/study-shows-how-high-fat-diets-increase-colon-cancer-risk
 
 
 
“Poor metabolic health linked to increased risk for colorectal cancer in normal-weight women” http://www.news-medical.net/news/20170201/Poor-metabolic-health-linked-to-increased-risk-for-colorectal-cancer-in-normal-weight-women.aspx
 
 
“Cheese, Milk, and Fatty Fish Can Help Fight Colon Cancer” https://munchies.vice.com/en_us/article/cheese-milk-and-fatty-fish-can-help-fight-colon-cancer
 
“Diet, exercise and aspirin: 3 tools to fight colon cancer” http://ktar.com/story/1314810/diet-exercise-aspirin-3-tools-fight-colon-cancer/
 
“Many Early Colon Cancers Linked to Inherited Genes” https://medlineplus.gov/news/fullstory_162574.html
 
“Study Supports Link Between Asbestos Exposure and Colon Cancer” http://www.asbestosnetwork.com/News/Study-Supports-Link-Between-Asbestos-Exposure-and-Colon-Cancer.shtml
 
“E.coli Bacteria Linked to Colon Cancer” http://www.ibtimes.co.uk/e-coli-bateria-linked-colon-cancer-375102
 
“Colorectal cancer prevalence linked to human papillomavirus: a systematic review with meta-analysis” http://www.scielo.br/scielo.php?pid=S1415-790X2016000400791&script=sci_arttext&tlng=en
 
“Colon cancer linked to viruses in beef, Nobel-winning scientist contends” http://www.scmp.com/lifestyle/health/article/1695757/colon-cancer-linked-viruses-beef-nobel-winning-scientist-contends
 
 
“Diet High in Choline Linked with Increased Risk of Colorectal Polyps. According to the results of a study published in the Journal of the National Cancer Institute, high intake of choline-a nutrient found in foods such as red meat, eggs, poultry, and dairy products-may be linked with an increased risk of colorectal polyps.” http://news.cancerconnect.com/diet-high-in-choline-linked-with-increased-risk-of-colorectal-polyps/
 
“High-Glycemic Foods Linked to Colon Cancer. These foods include breads, pastas, pancakes, and other carbohydrates made from refined “white” grains, as well as other processed or sugary foods such as cakes, cookies, and other snacks.” http://www.webmd.com/colorectal-cancer/news/20040203/high-glycemic-foods-linked-to-colon-cancer#1
 
“Low-carb diet cuts risk of colon cancer” https://www.utoronto.ca/news/low-carb-diet-cuts-risk-colon-cancer
 
“Common food additive promotes colon cancer in mice. Emulsifiers, which are added to most processed foods to aid texture and extend shelf life, can alter intestinal bacteria in a manner that promotes intestinal inflammation and colorectal cancer” https://www.sciencedaily.com/releases/2016/11/161107110639.htm
 
“Processed meats including bacon, hot dogs linked to colon cancer” http://www.cp24.com/news/processed-meats-including-bacon-hot-dogs-linked-to-colon-cancer-1.2627498
 
“Processed meat can cause colon cancer, World Health Organization says” http://www.cbc.ca/news/health/meat-cancer-world-health-organization-1.3288355
 
“Sweets, sugary snacks linked to colorectal cancer” http://www.cbsnews.com/news/sweets-sugary-snacks-linked-to-colorectal-cancer/
 
“Eating Nuts Linked to Lower Risk of Colon Cancer” http://www.livescience.com/54448-eating-nuts-may-lower-colon-cancer-risk.html
 
“Diabetes, high blood pressure linked to colon cancer recurrence” http://www.mcknights.com/news/diabetes-high-blood-pressure-linked-to-colon-cancer-recurrence/article/274064/
 
“Coffee consumption linked to lower risk of colorectal cancer” http://www.ctvnews.ca/health/coffee-consumption-linked-to-lower-risk-of-colorectal-cancer-1.2841834
“Alcohol Linked to Colorectal Cancer Risk” http://www.medscape.com/viewarticle/749886
 
“Excessive alcohol consumption favours high risk polyp or colorectal cancer occurrence among patients with adenomas: a case control study” http://gut.bmj.com/content/50/1/38.full
 
 
 
“High vitamin D levels linked to lower risk of colon cancer” http://www3.imperial.ac.uk/newsandeventspggrp/imperialcollege/newssummary/news_22-1-2010-13-46-0
 
 
 
 
“Anthocyanins in Purple, Blue and Red Foods Fight Colon Cancer” http://reliawire.com/anthocyanins-purple-blue-red-foods-fight-colon-cancer/
 
“Purple Potatoes Could Fight Colon Cancer” http://www.emaxhealth.com/1275/purple-potatoes-could-fight-colon-cancer
 
“Prunes reduce colon cancer risk by benefiting healthy gut bacteria” http://www.belmarrahealth.com/prunes-reduce-colon-cancer-risk-by-benefiting-healthy-gut-bacteria/
 
“BLACK RASPBERRIES A POTENTIALLY POWERFUL AGENT IN FIGHT AGAINST COLON CANCER” https://researchnews.osu.edu/archive/brberry.htm
 
 
 
 
 
 
 
“G‐protein coupled receptor 55 (GPR55), a lysophospholipid receptor, has been shown to play an important role in carcinogenesis. GPR55 is involved in the migratory behaviour of colon carcinoma cells and may serve as a pharmacological target for the prevention of metastasis.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688947/
“The putative cannabinoid receptor GPR55 promotes cancer cell proliferation.” http://www.ncbi.nlm.nih.gov/pubmed/21057532
 “L-α-lysophosphatidylinositol meets GPR55: a deadly relationship. Evidence points to a role of L-α-lysophosphatidylinositol (LPI) in cancer.” http://www.ncbi.nlm.nih.gov/pubmed/21367464
“Modulation of l-α-Lysophosphatidylinositol/GPR55 Mitogen-activated Protein Kinase (MAPK) Signaling by Cannabinoids*. Here, we report that the little investigated cannabis constituents CBDV, CBGA, and CBGV are potent inhibitors of LPI-induced GPR55 signaling. The phytocannabinoids Δ9-tetrahydrocannabivarin, cannabidivarin, and cannabigerovarin are also potent inhibitors of LPI. Our findings also suggest that GPR55 may be a new pharmacological target for the following C. sativa constituents: Δ9-THCV, CBDV, CBGA, and CBGV. These Cannabis sativa constituents may represent novel therapeutics targeting GPR55.” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3249141/
 “Cannabinoids and cancer: potential for colorectal cancer therapy.” https://www.ncbi.nlm.nih.gov/pubmed/16042581
 “The endogenous cannabinoid system protects against colonic inflammation”  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC385396/
 “Cannabinoids in intestinal inflammation and cancer. In vivo, cannabinoids – via direct or indirect activation of CB(1) and/or CB(2) receptors – exert protective effects in well-established models of intestinal inflammation and colon cancer. Pharmacological elevation of endocannabinoid levels may be a promising strategy to counteract intestinal inflammation and colon cancer.” http://www.ncbi.nlm.nih.gov/pubmed/19442536
 “Cannabinoids have become a novel therapeutic approach against colon cancer with protective and anti-tumoral effects on colorectal carcinoma cell lines and in animal models of colon cancer” http://impactjournals.com/oncoscience/index.php?pii=119 
 “Possible endocannabinoid control of colorectal cancer growth. Inhibitors of endocannabinoid inactivation may prove useful anticancer agents.” https://www.ncbi.nlm.nih.gov/pubmed/12949714
“Increased endocannabinoid levels reduce the development of precancerous lesions in the mouse colon. Cannabinoids have been licensed for clinical use as palliative treatment of chemotherapy, but increasing evidence shows antitumor actions of cannabinoid agonists on several tumor cells in vitro and in animal models” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2755791/

“Loss of cannabinoid receptor 1 accelerates intestinal tumor growth”  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2561258/

“Turned-off Cannabinoid Receptor Turns On Colorectal Tumor Growth” https://www.sciencedaily.com/releases/2008/08/080801074056.htm

“Turning CB1 back on and then treating with a cannabinoid agonist could provide a new approach to colorectal cancer treatment or prevention. Cannabinoids are a group of ligands that serve a variety of cell-signaling roles. Some are produced by the body internally (endocannabinoids). External cannabinoids include manmade versions and those present in plants, most famously the active ingredient in marijuana (THC).” http://www.news-medical.net/news/2008/08/03/40485.aspx

“Cannabinoid Receptor Activation Induces Apoptosis through Tumor Necrosis Factor α–Mediated Ceramide De novo Synthesis in Colon Cancer Cells. The present study shows that either CB1 or CB2 receptor activation induces apoptosis through ceramide de novo synthesis in colon cancer cells. ” http://clincancerres.aacrjournals.org/content/14/23/7691.long

“The cannabinoid delta(9)-tetrahydrocannabinol inhibits RAS-MAPK and PI3K-AKT survival signalling and induces BAD-mediated apoptosis in colorectal cancer cells. Here, we report that CB1 and CB2 cannabinoid receptors are expressed in human colorectal adenoma and carcinoma cells, and show for the first time that THC induces apoptosis in colorectal cancer cells. The use of THC, or selective targeting of the CB1 receptor, may represent a novel strategy for colorectal cancer therapy.” http://www.ncbi.nlm.nih.gov/pubmed/17583570

“Programmed Cell Death (Apoptosis)” http://www.ncbi.nlm.nih.gov/books/NBK26873/

“Cannabis-Linked Cell Receptor Might Help Prevent Colon Cancer” http://www.medicinenet.com/script/main/art.asp?articlekey=91511

“Chemopreventive effect of the non-psychotropic phytocannabinoid cannabidiol on experimental colon cancer. 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. It is concluded that cannabidiol exerts chemopreventive effect in vivo and reduces cell proliferation through multiple mechanisms.” https://www.ncbi.nlm.nih.gov/pubmed/22231745

“CBD-Rich Marijuana Fights Colon Cancer, New Study Finds” http://blog.sfgate.com/smellthetruth/2014/01/06/cbd-rich-marijuana-fights-colon-cancer-new-study-finds/

“Inhibition of colon carcinogenesis by a standardized Cannabis sativa extract with high content of cannabidiol. Cannabis-based medicines are useful adjunctive treatments in cancer patients.” http://www.ncbi.nlm.nih.gov/pubmed/24373545

“Cannabigerol (CBG) is a safe non-psychotropic Cannabis-derived cannabinoid. CBG hampers colon cancer progression in vivo and selectively inhibits the growth of colorectal cancer cells. CBG should be considered translationally in colorectal cancer prevention and cure.” http://www.ncbi.nlm.nih.gov/pubmed/25269802

“According to researchers at the University of Texas in Houston chemicals in marijuana could be a potential cure in the treatment of colon cancer.” http://www.digitaljournal.com/article/258161

“Cannabis compound clue to colon cancer”  https://www.newscientist.com/article/mg19926685.000-cannabis-compound-clue-to-colon-cancer/

“Marijuana takes on colon cancer” https://www.newscientist.com/article/dn14451-marijuana-takes-on-colon-cancer/

“Cannabinoids appear to kill tumor cells but do not affect their nontransformed counterparts and may even protect them from cell death. Tumor specimens revealed that THC had antiangiogenic and antiproliferative effects. CBD has also been demonstrated to exert a chemopreventive effect in a mouse model of colon cancer. In in vitro experiments involving colorectal cancer cell lines, the investigators found that CBD protected DNA from oxidative damage, increased endocannabinoid levels, and reduced cell proliferation. In addition, both plant-derived and endogenous cannabinoids have been studied for anti-inflammatory effects. A mouse study demonstrated that endogenous cannabinoid system signaling is likely to provide intrinsic protection against colonic inflammation. As a result, a hypothesis that phytocannabinoids and endocannabinoids may be useful in the risk reduction and treatment of colorectal cancer has been developed.” http://www.cancer.gov/about-cancer/treatment/cam/hp/cannabis-pdq#section/_7

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Cannabinoids and cancer: potential for colorectal cancer therapy.

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“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

Cannabisin B induces autophagic cell death by inhibiting the AKT/mTOR pathway and S phase cell cycle arrest in HepG2 cells.

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“This study investigates the anticancer properties of cannabisin B, purified from hempseed hull, in HepG2 human hepatoblastoma cells.

The results indicate that cannabisin B significantly inhibited cell proliferation by inducing autophagic cell death rather than typical apoptosis.

Cell viability transiently increased upon the addition of a low concentration of cannabisin B but decreased upon the addition of high concentrations.

Cannabisin B-induced changes in cell viability were completely inhibited by pre-treatment with 3-methyladenine (3-MA), indicating that the induction of autophagy by cannabisin B caused cell death.

Additionally, cannabisin B induced S phase cell cycle arrest in a dose-dependent manner.

Moreover, cannabisin B was found to inhibit survival signaling by blocking the activation of AKT and down-stream targets of the mammalian target of rapamycin (mTOR).

These findings suggest that cannabisin B possesses considerable antiproliferative activity and that it may be utilised as a promising chemopreventive agent against hepatoblastoma disease.”

http://www.ncbi.nlm.nih.gov/pubmed/23411211

http://www.thctotalhealthcare.com/category/liver-cancer-2/

Structure-dependent inhibitory effects of synthetic cannabinoids against 12-O-tetradecanoylphorbol-13-acetate-induced inflammation and skin tumour promotion in mice.

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“Whether and how synthetic cannabinoids affect inflammation and carcinogenesis has not been well studied. The present study was thus conducted to assess effects of synthetic cannabinoids on inflammation and carcinogenesis in vivo in mice…

The present results suggest that synthetic cannabinoids, such as JWH-018, -122 and -210, may be used as cancer chemopreventive agents in the future.”

http://www.ncbi.nlm.nih.gov/pubmed/23837590