Cannabinoids as a Potential New and Novel Treatment for Melanoma: A Pilot Study in a Murine Model

Erika Simmerman DO; Xu Qin DDS; Jack C. Yu MD, DMD; Babak Baban PhD  (October 2018)

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Malignant melanoma is a complex malignancy with significant morbidity and mortality. The incidence continues to rise, and despite advances in treatment, the prognosis is poor. Thus, it is necessary to develop novel strategies to treat this aggressive cancer. Synthetic cannabinoids have been implicated in inhibiting cancer cell proliferation, reducing tumor growth, and reducing metastasis. We developed a unique study focusing on the effects of treatment with a cannabinoid derivative on malignant melanoma tumors in a murine model. We demonstrate a potential beneficial therapeutic effect of cannabinoids, which could influence the course of melanoma in a murine model. Increased survival and less tumorgenicity are novel findings that should guide research to better understand the mechanisms by which cannabinoids could be utilized as adjunctive treatment of cancer, specifically melanoma. Further studies are necessary to evaluate this potentially new and novel treatment of malignant melanoma.

Cannabinoid WIN 55,212-2 induces cell cycle arrest and apoptosis, and inhibits proliferation, migration, invasion, and tumor growth in prostate cancer in a cannabinoid-receptor 2 dependent manner.

Roberto D, Klotz LH, Venkateswaran V  (September 2018)

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Cannabinoids have demonstrated anticarcinogenic properties in a variety of malignancies, including in prostate cancer. In the present study, we explored the anti-cancer effects of the synthetic cannabinoid WIN 55,212-2 (WIN) in prostate cancer. WIN significantly reduced prostate cancer cell proliferation, migration, invasion, induced apoptosis, and arrested cells in Go/G1 phase in a dose-dependent manner. Mechanistic studies revealed these effects were mediated through a pathway involving cell cycle regulators p27, Cdk4, and pRb. Pre-treatment with a CB2 antagonist, AM630, followed by treatment with WIN resulted in a reversal of the anti-proliferation and cell cycle arrest previously seen with WIN alone. In vivo, administration of WIN resulted in a reduction in the tumor growth rate compared to control (P < 0.05). The following study provides evidence supporting the use of WIN as a novel therapeutic for prostate cancer.

Cannabidiol (CBD) Is a Novel Inhibitor for Exosome and Microvesicle (EMV) Release in Cancer.

Kosgodage US, Mould R, Henley AB, Nunn AV, Guy GW, Thomas EL, Inal JM, Bell JD, Lange S  (August 2018)

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Recent studies show that EMV-inhibiting agents can sensitize cancer cells to chemotherapeutic agents and reduce cancer growth in vivo. Cannabidiol (CBD), a phytocannabinoid derived from Cannabis sativa, has anti-inflammatory and anti-oxidant properties, and displays anti-proliferative activity. Here we report a novel role for CBD as a potent inhibitor of EMV release from three cancer cell lines: prostate cancer (PC3), hepatocellular carcinoma (HEPG2) and breast adenocarcinoma (MDA-MB-231). CBD significantly reduced exosome release in all three cancer cell lines, and also significantly, albeit more variably, inhibited microvesicle release.

Anti‐tumoural actions of cannabinoids

Burkhard Hinz and Robert Ramer (July 2018)

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Although the clinical use of cannabinoid receptor ligands is limited by their psychoactivity, nonpsychoactive compounds, such as cannabidiol, have gained attention due to preclinically established anticancer properties and a favourable risk‐to‐benefit profile. Thus, cannabinoids may complement the currently used collection of chemotherapeutics, as a broadly diversified option for cancer treatment, while counteracting some of their severe side effects.

Cannabis for the Management of Cancer Symptoms: THC Version 2.0?

Guzmán, Manuel  (May 2018)

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Nowadays, on practical grounds, interpretation of empirical records on medical cannabis use, combined with a rational application of our current understanding of the mechanism of cannabinoid action, as well as some “trial and error,” may be the only way to delineate which cannabis preparations may adjust best (in terms of efficacy and tolerability) to the specific needs of each patient at each disease stage. Hopefully, this relatively fragile strategy will evolve in the near future for the appreciable benefit of the patient.

Enhancing the Therapeutic Efficacy of Cancer Treatment With Cannabinoids

Sayeda Yasmin-Karim, Michele Moreau, Romy Mueller, Neeharika Sinha, Raymond Dabney, Allen Herman and Wilfred Ngwa  (May 2018)

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Pancreatic cancer is one of the deadliest cancers, with a dismal 5-year survival rate of less than 5% (24, 25). Meanwhile lung cancer is amongst the top killers, with a growing burden, especially in low- and middle-income countries with limited access to treatment (19). There is, thus, great need to develop more effective and accessible therapeutic approaches for treating these cancers. Our results suggest that the use of a combination of strategies could allow for greater therapeutic efficacy when using CBDs for cancer treatment. The in vitro study results showing synergistic outcomes when using CBDs in combination with RT are in consonance with previous work highlighted in recent reviews (1, 2).

Inhibition of Fatty Acid Amide Hydrolase Inhibits Tumor Growth In A Murine Model Of Breast Cancer

Sun, Jeffrey Ching-Ruey  (December 2017)

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By inhibiting FAAH using the inhibitor URB 597, we can harness the body’s natural production of endocannabinoids to encourage apoptosis in cancer cells. We have shown through in vitro models that FAAH is present in breast cancer and increased apoptosis can be achieved through the addition of exogenous endocannabinoids and URB 597. Here, we develop an in vitro model of breast cancer using GFP & luciferase transduced breast cancer cells and an immune-deficient mouse model.

Effect of Phytocannabinoids and Endocannabinoids on Ovarian Cancer Cell Proliferation

Bert Crawford (March 2017)

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The phytocannabinoids tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) and the endocannabinoids 2-arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol (2-AG) exhibit antiproliferative effect on cancer cells derived from diiferent organs, including thyroid, brain, prostate and breast. THC and the endocannabinoids are known agonists at the G-protein coupled receptors (CB1 and CB2), which appear to mediate the antiproliferative effect on some of the cancer cells. CBD’s antiproliferative effect, on the other hand, is mediated via CB receptor-independent mechanism. In this study, I hypothesized that ovarian cancer cell proliferation will be also inhibited by these cannabinoids.

Anticancer mechanisms of cannabinoids

G. Velasco, PhD, C. Sánchez, PhD, and M. Guzmán, PhD (March 2016)

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In this review, we discuss the current understanding of cannabinoids as antitumour agents, focusing on recent discoveries about their molecular mechanisms of action, including resistance mechanisms and opportunities for their use in combination therapy. Those observations have already contributed to the foundation for the development of the first clinical studies that will analyze the safety and potential clinical benefit of cannabinoids as anticancer agents.

Proapoptotic effect of endocannabinoids in prostate cancer cells

O. Orellana-Serradell, C. E. Poblete, C. Sanchez, E. A. Castellón, I. Gallegos, C. Huidobro, M. N. Llanos, H. R. Contreras  (January 2015)

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Treatment with endocannabinoids resulted in an increase in the percentage of apoptotic cells as determined by Annexin V assays and caused an increase in the levels of activated caspase-3 and a reduction in the levels of Bcl-2 confirming that the reduction in cell viability noted in the MTT assay was caused by the activation of the apoptotic pathway. Finally, we observed that endocannabinoid treatment activated the Erk pathway and at the same time, produced a decrease in the activation levels of the Akt pathway. Based on these results, we suggest that endocannabinoids may be a beneficial option for the treatment of prostate cancer that has become nonresponsive to common therapies.

Endocannabinoids and Cancer

Guillermo Velasco, Cristina Sánchez, Manuel Guzmán  (2015)

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A large body of evidence shows that cannabinoids, in addition to their well-known palliative effects on some cancer-associated symptoms, can reduce tumour growth in animal models of cancer. They do so by modulating key cell signalling pathways involved in the control of cancer cell proliferation and survival. In addition, cannabinoids inhibit angiogenesis and cell proliferation in different types of tumours in laboratory animals. By contrast, little is known about the biological role of the endocannabinoid system in cancer physio-pathology, and several studies suggest that it may be over-activated in cancer.

Regulation of circulating endocannabinoids associated with cancer and metastases in mice and humans

Sebastian Sailler, Katja Schmitz, Elke Jäger, Nerea Ferreiros, Sabine Wicker, Katja Zschiebsch, Geethanjali Pickert, Gerd Geisslinger, Carmen Walter, Irmgard Tegeder, and Jörn Lötsch (April 2014)

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The endocannabinoid system was subject to cancer-associated regulations to an extent that led to measurable changes in circulating endocannabinoid levels, emphasizing the importance of the endocannabinoid system in the pathophysiology of cancer.