Activation of Cannabinoid Receptor 2 Prevents Colitis-Associated Colon Cancer through Myeloid Cell De-activation Upstream of IL-22 Production

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” Here we show that delta-9-tetrahydrocannabinol (THC) attenuates colitis-associated colon cancer and colitis induced by anti-CD40.
 THC can prevent the development of colitis-associated colon cancer in mice.”

“Study reveals how cannabinoids may be useful to prevent colon cancer”   https://medicalxpress.com/news/2020-09-reveals-cannabinoids-colon-cancer.html

“Key cannabis chemical may help prevent colon cancer, researchers say”   https://www.heraldmailmedia.com/news/nation/key-cannabis-chemical-may-help-prevent-colon-cancer-researchers-say/article_7afd0a72-eead-57f0-a1d3-006be62b7469.html

“Treatment with a cannabinoid prevented the development of colon cancers in mice” https://www.news-medical.net/news/20200915/Treatment-with-a-cannabinoid-prevented-the-development-of-colon-cancers-in-mice.aspx

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Cannabinoids and Prostate Cancer: A Systematic Review of Animal Studies

ijms-logo“Prostate cancer is a major cause of death among men worldwide.

Recent preclinical evidence implicates cannabinoids as powerful regulators of cell growth and differentiation, as well as potential anti-cancer agents.

The aim of this review was to evaluate the effect of cannabinoids on in vivo prostate cancer models.

We identified six studies that were all found to be based on in vivo/xenograft animal models.

All studies have reported that the treatment of prostate cancers in in vivo/xenograft models with various cannabinoids decreased the size of the tumor, the outcomes of which depended on the dose and length of treatment.

Within the limitation of these identified studies, cannabinoids were shown to reduce the size of prostate cancer tumors in animal models.”

https://pubmed.ncbi.nlm.nih.gov/32872551/

https://www.mdpi.com/1422-0067/21/17/6265

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Cannabis sativa L. Extracts can reverse drug resistance in colorectal carcinoma cells in vitro

Synergy“Multidrug resistance (MDR) to known chemotherapeutic agents is increasing while the development of new drugs is lacking behind. Combination therapies might increase the development of effective treatment.

Anticancer properties of C. sativa L. have been extensively studied against various cancer cell lines but research on its effectiveness on MDR in cancer is less documented.

Aim

To determine the potential resistant reversal of the cytostatic drug doxorubicin by C. sativa L. extracts through combination studies.

Method

The cytotoxic effect of the different C. sativa L. extracts was assessed against a panel of human colon cancer cells (HT-29, Caco-2, HCT-15, LS513) and normal colon cells (CCD-18Co) by MTT assay. Drug-extract combination studies were performed on HCT-15 and LS513 MDR cells.

Results

DCM: methanol- and H2O extracts moderately inhibited the growth in HCT-15 and LS513 cells (IC50: 20–100 μg/ml). DCM- and H2O extracts potently inhibited HT-29 cell growth. Higher concentrations (100 μg/ml) of the hexane- and DCM- extracts slightly stimulated growth in Caco-2 cells. All the C. sativa L. extracts were more cytotoxic towards the cancerous cells than towards the normal colon cells. Combination studies between doxorubicin and the C. sativa L. extracts revealed synergistic growth inhibitory effects (CI < 1). The sensitivity to doxorubicin increased in HCT-15 and LS513 cells by 2.08- to 74.07-fold and 2.21- to 300.7-fold, respectively, compared to verapamil which improved it by 1.41-fold and 0.05-fold, respectively.

Conclusion

C. sativa L. extracts possess direct selective cytotoxic effect on colon cells and have a potential to reverse doxorubicin resistance.”

https://www.sciencedirect.com/science/article/abs/pii/S2213713019300021

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Anti-proliferative and cytotoxic effect of cannabidiol on human cancer cell lines in presence of serum

 BMC Research Notes | Home page“Objective: Cannabinoids are able to reduce tumor growth in xenograft models, but their therapeutic potential as anti-cancer drugs in humans is unclear yet. In vitro studies of the effect of cannabinoids on cancer cells are often carried out in absence of serum or in low serum concentration (i.e. 0.5% serum), conditions that limit cellular growth and therefore can increase the response of cells to additional challenges such as the presence of cannabinoids. However, the tumor microenvironment can be teaming with growth factors. In this study we assessed the viability and proliferation of cancer cells treated with cannabidiol in presence of a serum concentration that commonly sustains cell growth (10% serum).

Results: The results show that cannabidiol exerts a markedly different effect on the viability of the human HT-29 cancer cell line when cultured in presence of 0.5% serum in comparison to 10% serum, displaying a cytotoxic effect only in the former situation. In presence of 10% serum, no inhibitory effect of cannabidiol on DNA replication of HT-29 cells was detected, and a weak inhibition was observed for other cancer cell lines. These results indicate that the effect of cannabidiol is cell context-dependent being modulated by the presence of growth factors.”

https://pubmed.ncbi.nlm.nih.gov/32819436/

“The cannabis plant has a therapeutic potential to treat a wide range of diseases, including cancer.”

https://bmcresnotes.biomedcentral.com/articles/10.1186/s13104-020-05229-5

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Roles of Cannabinoids in Melanoma: Evidence from In Vivo Studies

ijms-logo“Melanoma is the fourth most common type of cancer diagnosed in Australians after breast, prostate, and colorectal cancers. While there has been substantial progress in the treatment of cancer in general, malignant melanoma, in particular, is resistant to existing medical therapies requiring an urgent need to develop effective treatments with lesser side effects.

Several studies have shown that “cannabinoids”, the major compounds of the Cannabis sativaL. plant, can reduce cell proliferation and induce apoptosis in melanoma cells.

Despite prohibited use of Cannabis in most parts of the world, in recent years there have been renewed interests in exploiting the beneficial health effects of the Cannabis plant-derived compounds. Therefore, the aim of this study was in the first instance to review the evidence from in vivo studies on the effects of cannabinoids on melanoma.

The findings revealed cannabinoids, individually or combined, reduced tumor growth and promoted apoptosis and autophagy in melanoma cells.

Further preclinical and animal studies are required to determine the underlying mechanisms of cannabinoids-mediated inhibition of cancer-signaling pathways. Well-structured, randomized clinical studies on cannabinoid use in melanoma patients would also be required prior to cannabinoids becoming a viable and recognized therapeutic option for melanoma treatment in patients.”

https://pubmed.ncbi.nlm.nih.gov/32839414/

https://www.mdpi.com/1422-0067/21/17/6040

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Cannabinoid Effects on Experimental Colorectal Cancer Models Reduce Aberrant Crypt Foci (ACF) and Tumor Volume: A Systematic Review

See the source image “Colorectal cancer represents a heavy burden for health systems worldwide, being the third most common cancer worldwide. Despite the breakthroughs in medicine, current chemotherapeutic options continue to have important side effects and may not be effective in preventing disease progression.

Cannabinoids might be substances with possible therapeutic potential for cancer because they can attenuate the side effects of chemotherapy and have antiproliferative and antimetastatic effects.

We aim to determine, through a systematic review of experimental studies performed on animal CRC models, if cannabinoids can reduce the formation of preneoplastic lesions (aberrant crypt foci), number, and volume of neoplastic lesions.

Results: Eight in vivo experimental studies were included in the analysis after the full-text evaluation. Seven studies were azoxymethane (AOM) colorectal cancer models, and four studies were xenograft models. Cannabidiol botanical substance (CBD BS) and rimonabant achieved high aberrant crypt foci (ACF) reduction (86% and 75.4%, respectively). Cannabigerol, O-1602, and URB-602 demonstrated a high capacity for tumor volume reduction. Induction of apoptosis, interaction with cell survival, growth pathways, and angiogenesis inhibition were the mechanisms extracted from the studies that explain cannabinoids’ actions on CRC.

Conclusions: Cannabinoids have incredible potential as antineoplastic agents as experimental models demonstrate that they can reduce tumor volume and ACF formation. It is crucial to conduct more experimental studies to understand the pharmacology of cannabinoids in CRC better.”

https://pubmed.ncbi.nlm.nih.gov/32765628/

“Current literature findings demonstrate that cannabinoids might have potential as antineoplastic agents because they can reduce tumor volume and ACF formation.”

https://www.hindawi.com/journals/ecam/2020/2371527/

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The Effects of Cannabidiol and Prognostic Role of TRPV2 in Human Endometrial Cancer

ijms-logo“Several studies support, both in vitro and in vivo, the anti-cancer effects of cannabidiol (CBD), a transient receptor potential vanilloid 2 (TRPV2) ligand. TRPV2, often dysregulated in tumors, is associated with altered cell proliferation and aggressiveness.

Endometrial cancer (EC) is historically divided in type I endometrioid EC and type II non-endometrioid EC, associated with poor prognosis. Treatment options with chemotherapy and combinations with radiation showed only limited efficacy. Since no data are reported concerning TRPV2 expression as well as CBD potential effects in EC, the aim of this study was to evaluate the expression of TRPV2 in biopsies and cell lines as well as the effects of CBD in in vitro models. Overall survival (OS), progression-free survival (PFS), cell viability, migration, and chemo-resistance have been evaluated.

Results show that TRPV2 expression increased with the malignancy of the cancer tissue and correlated with shorter PFS (p = 0.0224). Moreover, in vitro TRPV2 over-expression in Ishikawa cell line increased migratory ability and response to cisplatin. CBD reduced cell viability, activating predominantly apoptosis in type I cells and autophagy in mixed type EC cells. The CBD improved chemotherapeutic drugs cytotoxic effects, enhanced by TRPV2 over-expression. Hence, TRPV2 could be considered as a marker for optimizing the therapy and CBD might be a useful therapeutic option as adjuvant therapy.”

https://pubmed.ncbi.nlm.nih.gov/32751388/

https://www.mdpi.com/1422-0067/21/15/5409

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Cytotoxic Effects of Cannabinoids on Human HT-29 Colorectal Adenocarcinoma Cells: Different Mechanisms of THC, CBD, and CB83

ijms-logo “In this study, we investigated the effects of exposition to IC50 dose for 24 h of a new synthetic cannabinoid (CB83) and of phytocannabinoids Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) on HT-29 colorectal carcinoma cells. Cell viability and proliferative activity evaluated using the MTT, lactate dehydrogenase (LDH), and CyQUANT assays showed that cell viability was significantly affected when CB83, THC, and CBD were administered to cells.

The results obtained showed that the reduced glutathione/oxidized glutathione ratio was significantly reduced in the cells exposed to CBD and significantly increased in the cells treated with the CB83 when compared to the controls. CBD treatment causes a significant increase in malondialdehyde content. The catalase activity was significantly reduced in HT-29 cells after incubation with CB83, THC, and CBD. The activities of glutathione reductase and glutathione peroxidase were significantly increased in cells exposed to THC and significantly decreased in those treated with CBD. The ascorbic acid content was significantly reduced in cells exposed to CB83, THC, and CBD. The ultrastructural investigation by TEM highlighted a significantly increased percentage of cells apoptotic and necrotic after CB83 exposition. The Annexin V-Propidium Iodide assay showed a significantly increased percentage of cells apoptotic after CB83 exposition and necrotic cells after CBD and THC exposition.

Our results proved that only CBD induced oxidative stress in HT-29 colorectal carcinoma cells via CB receptor-independent mechanisms and that CB83 caused a mainly CB2 receptor-mediated antiproliferative effect comparable to 5-Fuorouracil, which is still the mainstay drug in protocols for colorectal cancer.”

https://pubmed.ncbi.nlm.nih.gov/32752303/

https://www.mdpi.com/1422-0067/21/15/5533

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Anti-Cancer Potential of Cannabinoids, Terpenes, and Flavonoids Present in Cannabis

cancers-logo“In recent years, and even more since its legalization in several jurisdictions, cannabis and the endocannabinoid system have received an increasing amount of interest related to their potential exploitation in clinical settings. Cannabinoids have been suggested and shown to be effective in the treatment of various conditions. In cancer, the endocannabinoid system is altered in numerous types of tumours and can relate to cancer prognosis and disease outcome. Additionally, cannabinoids display anticancer effects in several models by suppressing the proliferation, migration and/or invasion of cancer cells, as well as tumour angiogenesis. However, the therapeutic use of cannabinoids is currently limited to the treatment of symptoms and pain associated with chemotherapy, while their potential use as cytotoxic drugs in chemotherapy still requires validation in patients. Along with cannabinoids, cannabis contains several other compounds that have also been shown to exert anti-tumorigenic actions. The potential anti-cancer effects of cannabinoids, terpenes and flavonoids, present in cannabis, are explored in this literature review.”

https://pubmed.ncbi.nlm.nih.gov/32708138/

https://www.mdpi.com/2072-6694/12/7/1985

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Enhancing ovarian cancer conventional chemotherapy through the combination with cannabidiol loaded microparticles

 European Journal of Pharmaceutics and Biopharmaceutics“In this work, we evaluated, for the first time, the antitumor effect of cannabidiol (CBD) as monotherapy and in combination with conventional chemotherapeutics in ovarian cancer and developed PLGA-microparticles as CBD carriers to optimize its anticancer activity.

Spherical microparticles, with a mean particle size around 25 µm and high entrapment efficiency were obtained. Microparticles elaborated with a CBD:polymer ratio of 10:100 were selected due to the most suitable release profile with a zero-order CBD release (14.13±0.17 μg/day/10 mg Mps) for 40 days.

The single administration of this formulation showed an in vitro extended antitumor activity for at least 10 days and an in ovo antitumor efficacy comparable to that of CBD in solution after daily topical administration (≈1.5-fold reduction in tumor growth vs control). The use of CBD in combination with paclitaxel (PTX) was really effective.

The best treatment schedule was the pre+co-administration of CBD (10µM) with PTX. Using this protocol, the single administration of microparticles was even more effective than the daily administration of CBD in solution, achieving a ≈10- and 8- fold reduction in PTX IC50 respectively. This protocol was also effective in ovo. While PTX conducted to a 1.5-fold tumor growth inhibition, its combination with both CBD in solution (daily administered) and 10-Mps (single administration) showed a 2-fold decrease.

These results show the promising potential of CBD-Mps administered in combination with PTX for ovarian cancer treatment, since it would allow to reduce the administered dose of this antineoplastic drug maintaining the same efficacy and, as a consequence, reducing PTX adverse effects.”

https://pubmed.ncbi.nlm.nih.gov/32682943/

https://www.sciencedirect.com/science/article/abs/pii/S0939641120302113?via%3Dihub

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