Category Archives: Cancer

Synthetic Cannabinoid Activity Against Colorectal Cancer Cells

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“Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide, and new therapeutic strategies are still required. Here we screened a synthetic cannabinoid library to identify compounds that uniformly reduce the viability of seven CRC cell lines.

We identified 10 compounds from the library that were able to reduce cell viability of CRC cell lines.

Conclusion: We identified three families of cannabinoid compounds that reduce CRC cell viability through a noncanonical receptor mechanism. Future modification of these compounds may lead to the development of novel therapies to treat this disease.”

https://www.liebertpub.com/doi/10.1089/can.2018.0065

“Cannabinoid compounds may inhibit growth of colon cancer cells”  https://news.psu.edu/story/557660/2019/02/06/research/cannabinoid-compounds-may-inhibit-growth-colon-cancer-cells

“CANNABIS COMPOUNDS SLOW COLON CANCER IN THE LAB”  https://www.futurity.org/cannabinoids-colon-cancer-1975272/

“Synthetic cannabis may stop colorectal cancer from growing, study suggests”  https://www.dailymail.co.uk/health/article-6674275/Synthetic-cannabis-stop-colorectal-cancer-growing-study-suggests.html

Cannabinoids: the lows and the highs of chemotherapy-induced nausea and vomiting.

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“Despite remaining one of the most widely abused drugs worldwide, Cannabis sativa exhibits remarkable medicinal properties. The phytocannabinoids, cannabidiol and Δ-9-tetrahydrocannabinol, reduce nausea and vomiting, particularly during chemotherapy. This is attributed to their ability to reduce the release of serotonin from enterochromaffin cells in the small intestine, which would otherwise orchestrate the vomiting reflex. Although there are many preclinical and clinical studies on the effects of Δ-9-tetrahydrocannabinol during nausea and vomiting, little is known about the role that cannabidiol plays in this scenario. Since cannabidiol does not induce psychotropic effects, in contrast to other cannabinoids, its use as an anti-emetic is of great interest. This review aims to summarize the available literature on cannabinoid use, with a specific focus on the nonpsychotropic drug cannabidiol, as well as the roles that cannabinoids play in preventing several other adverse side effects of chemotherapy including organ toxicity, pain and loss of appetite.”

https://www.ncbi.nlm.nih.gov/pubmed/30720344

https://www.futuremedicine.com/doi/10.2217/fon-2018-0530

New Prospect for Cancer Cachexia: Medical Cannabinoid.

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“Cachexia is a common term for the wasting symptoms which may appear in almost every chronic illness, such as AIDS, tuberculosis, and cancer. Cancer cachexia (CCA) is a result of the interaction between the host and the tumor, mainly manifested in short-term wasting, malnutrition, and so on. Due to the chronic food shortages, absorption dysfunction and metabolic disorders, all of these eventually lead to hypoimmunity, organ failure, and higher susceptibility to pathogenic microorganisms. And then increased morbidity and mortality rates as well as reduced tolerance to anti-cancer treatments will be resulted in patients with CCA. Up to now, no standard guidelines have been established for cachexia treatment. Moreover, progestagens, the only drugs approved by FDA for cancer-related cachexia, can only increase adipose tissue and have not been confirmed to augment lean body mass. Cannabinoid, such as Δ-9-tetrahydrocannabinol (THC) and cannabidiol, is one of a class of diverse chemical compounds. Previous studies have showed that cannabinoid had considerable potential to improve the appetite, body weight, body fat level, caloric intake, mood, quality of life in kinds of diseases. This review will elaborate the anti-CCA role of cannabinoid and explore that whether cannabinoid is effective for CCA and provide a basis for guiding clinical drug use.”

https://www.ncbi.nlm.nih.gov/pubmed/30719170

http://www.jcancer.org/v10p0716.htm

Role of miRNA in the regulation of cannabidiol-mediated apoptosis in neuroblastoma cells.

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“Neuroblastoma (NBL) is one of the most common childhood cancers that originate from the immature nerve cells of the sympathetic system. Studies with NBL cancers have also shown that miRNAs are dysregulated and may play a critical role in pathogenesis.

Cannabidiol (CBD) is a non-psychoactive compound found in marijuana which has been previously shown by our laboratory and others to induce apoptosis in cancer cells. However, there are no studies reported to test if CBD mediates these effects through regulation of miRNA.

In the current study, therefore, we investigated if CBD induces apoptosis in human NBL cell lines, SH SY5Y and IMR-32, and if it is regulated by miRNA.

Our data demonstrated that CBD induces apoptosis in NBL cells through activation of serotonin and vanilloid receptors. We also found that caspase-2 and -3 played an important role in the induction of apoptosis. CBD also significantly reduced NBL cell migration and invasion in vitro.

Furthermore, CBD blocked mitochondrial respiration and caused a shift in metabolism towards glycolysis. CBD altered the expression of miRNA specifically, down-regulating hsa-let-7a and upregulating hsa-mir-1972. Downregulation of let-7a increased expression of target caspase-3, and growth arrest specific-7 (GAS-7) genes. Upregulation of hsa-mir-1972 caused decreased expression of BCL2L1 and SIRT2 genes.

Together, our studies suggest that CBD-mediated apoptosis in NBL cells is regulated by miRNA.”

 https://www.ncbi.nlm.nih.gov/pubmed/30713602

A Comprehensive Review of Cannabis in Patients with Cancer: Availability in the USA, General Efficacy, and Safety.

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 “As the legalization of medical cannabis continues across the USA, oncology care providers will be increasingly asked to provide recommendations regarding its use in the cancer setting.

In this article, we review recent literature that analyzes cannabis use specifically in patients with cancer and provide an accessible guide for clinicians, researchers, and patients.

We aimed to answer questions about the availability of cannabis in the USA, the trials supporting its use in the cancer setting, and the important factors to consider related to safety. Thirty states plus the District of Columbia have established comprehensive medical cannabis programs, each with different regulations and products available.

 

In June 2018, Epidiolex, a cannabis extraction product containing 99% CBD, was approved to treat refractory seizures; however, whole-plant products and non-prescription extraction products dominate the market.

 

Recent randomized, placebo-controlled studies of nabiximols (Sativex) in patients with refractory cancer-pain have largely shown no significant benefits. Conversely, large observational studies suggest patients with cancer using cannabis report significant improvement of many common symptoms.

 

Cannabis use appears well tolerated, with few serious adverse effects reported. Though prospective clinical trials are needed to provide the robust data required to establish the proper role of cannabinoid and cannabis-based therapy in cancer patients, physicians can draw upon the knowledge currently available to have informed discussions with their patients.”

https://www.ncbi.nlm.nih.gov/pubmed/30707319

https://link.springer.com/article/10.1007%2Fs11912-019-0757-7

Synthetic Cannabinoids Influence the Invasion of Glioblastoma Cell Lines in a Cell- and Receptor-Dependent Manner.

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“The current treatment of glioblastoma is not sufficient, since they are heterogeneous and often resistant to chemotherapy.

Earlier studies demonstrated effects of specific cannabinoid receptor (CB) agonists on the invasiveness of glioblastoma cell lines, but the exact mechanism remained unclear.

Three human glioblastoma cell lines were treated with synthetic CB ligands. The effect of cannabinoids on microRNAs (miRs), Akt, and on the expression of proliferation and apoptosis markers were analyzed.

Furthermore, in a model of organotypic hippocampal slice cultures cannabinoid mediated changes in the invasiveness were assessed. MicroRNAs and the activation of Akt which are related to cell migration, apoptosis, and proliferation were evaluated and found not to be associated with changes in the invasiveness after treatment with CB ligands.

Also proliferation and/or apoptosis were not altered after treatment. The effects of cannabinoids on invasiveness could be blocked by the application of receptor antagonists and are likely mediated via CB₁/CB₂.

In conclusion, our results suggest that cannabinoids can influence glioblastoma cell invasion in a receptor and cell type specific manner that is independent of proliferation and apoptosis. Thus, cannabinoids can potentially be used in the future as an addition to current therapy.”

https://www.ncbi.nlm.nih.gov/pubmed/30709059
https://www.mdpi.com/2072-6694/11/2/161

Potential Use of Cannabinoids for the Treatment of Pancreatic Cancer.

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“Cannabinoid extracts may have anticancer properties, which can improve cancer treatment outcomes.

The aim of this review is to determine the potentially utility of cannabinoids in the treatment of pancreatic cancer.

Results: Cannabinol receptors have been identified in pancreatic cancer with several studies showing in vitroantiproliferative and proapoptotic effects. The main active substances found in cannabis plants are cannabidiol (CBD) and tetrahydrocannabinol (THC). There effects are predominately mediated through, but not limited to cannabinoid receptor-1, cannabinoid receptor-2, and G-protein-coupled receptor 55 pathways. In vitro studies consistently demonstrated tumor growth-inhibiting effects with CBD, THC, and synthetic derivatives. Synergistic treatment effects have been shown in two studies with the combination of CBD/synthetic cannabinoid receptor ligands and chemotherapy in xenograft and genetically modified spontaneous pancreatic cancer models. There are, however, no clinical studies to date showing treatment benefits in patients with pancreatic cancer.

Conclusions: Cannabinoids may be an effective adjunct for the treatment of pancreatic cancer. Data on the anticancer effectiveness of various cannabinoid formulations, treatment dosing, precise mode of action, and clinical studies are lacking.”

 https://www.ncbi.nlm.nih.gov/pubmed/30706048
“Endogenous cannabinoids, synthetic or cannabis extracted from plants, can reduce tumor invasion and growth, induce tumor cell death, and inhibit tumor angiogenesis via cannabinoid receptor or receptor-independent pathways. Cannabinoid receptors appear to be highly expressed in pancreatic cancer compared with normal pancreatic tissue. CBD and THC appear to have antiproliferative and proapoptotic effects.”
https://www.liebertpub.com/doi/10.1089/pancan.2018.0019

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

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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.

RESULTS:

A significant decrease in tumor size was detected in mice treated with CBD when compared with the control group (P = 0.01). The survival curve of melanoma tumors treated with CBD increased when compared with the control group and was statistically significant (P = 0.04). The growth curve and survival curve of melanoma tumors treated with Cisplatin were significantly decreased and increased, respectively, when compared with the control and CBD-treated groups. Mice treated with Cisplatin demonstrated the longest survival time, but the quality of life and movement of CBD-treated mice were observed to be better.

CONCLUSIONS:

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.”

https://www.ncbi.nlm.nih.gov/pubmed/30691796

https://www.journalofsurgicalresearch.com/article/S0022-4804(18)30626-7/fulltext

Prospects for the Use of Cannabinoids in Oncology and Palliative Care Practice: A Review of the Evidence.

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 cancers-logo“There is an increased interest in the use of cannabinoids in the treatment of symptoms in cancer and palliative care patients. Their multimodal action, in spite of limited efficacy, may make them an attractive alternative, particularly in patients with multiple concomitant symptoms of mild and moderate intensity. There is evidence to indicate cannabis in the treatment of pain, spasticity, seizures, sleep disorders, nausea and vomiting, and Tourette syndrome. Although the effectiveness of cannabinoids is limited, it was confirmed in neuropathic pain management and combination with opioids. A relatively favorable adverse effects profile, including no depressive effect on the respiratory system, may make cannabis complement a rather narrow armamentarium that is in the disposition of a palliative care professional.”

https://www.ncbi.nlm.nih.gov/pubmed/30678303

https://www.mdpi.com/2072-6694/11/2/129

Cannabidiol-induced apoptosis is mediated by activation of Noxa in human colorectal cancer cells.

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“Cannabidiol (CBD), one of the compounds present in the marijuana plant, has anti-tumor properties, but its mechanism is not well known.

This study aimed to evaluate the apoptotic action of CBD in colorectal cancer (CRC) cells, and focused on its effects on the novel pro-apoptotic Noxa-reactive oxygen species (ROS) signaling pathway.

CBD experiments were performed using the CRC cell lines HCT116 and DLD-1. CBD induced apoptosis by regulating many pro- and anti-apoptotic proteins, of which Noxa showed significantly higher expression. To understand the relationship between Noxa and CBD-induced apoptosis, Noxa levels were downregulated using siRNA, and the expression of apoptosis markers decreased.

After ROS production was blocked, the level of Noxa also decreased, suggesting that ROS is involved in the regulation of Noxa, which along with ROS is a well-known pro-apoptotic signaling agents. As a result, CBD induced apoptosis in a Noxa-and-ROS-dependent manner.

Taken together, the results obtained in this study re-demonstrated the effects of CBD treatment in vivo, thus confirming its role as a novel, reliable anticancer drug.”

https://www.ncbi.nlm.nih.gov/pubmed/30660647

“Our results using cells, mice, and patient-derived cells strongly suggest, for the first time, that that CBD can cause Noxa-induced cell death. These results suggest that that CBD has important implications for the potential treatment of human CRC.”