Category Archives: Cancer

Bioactive spirans and other constituents from the leaves of Cannabis sativa f. sativa.

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“In this paper, 17 compounds (1-17) were isolated from the leaves of Hemp (Cannabis sativa f. sativa). Among the isolates, two were determined to be new spirans: cannabispirketal (1), and α-cannabispiranol 4′-O-β-D-glucopyranose (2) by 1D and 2D NMR spectroscopy, LC-MS, and HRESIMS. The known compounds 7, 8, 10, 13, 15, and 16 were isolated from Hemp (C. sativa f. sativa) for the first time. Furthermore, compounds 8 and 13 were isolated from the nature for the first time. All isolated compounds were evaluated for cytotoxicity on different tissue-derived passage cancer cell lines through cell viability and apoptosis assay. Among these compounds, compounds 5, 9 and 16 exhibited a broad-spectrum antitumor effect via inhibiting cell proliferation and promoting apoptosis. These results obtained have provided valuable clues to the understanding of the cytotoxic profile for these isolated compounds from Hemp (C. sativa f. sativa).”

https://www.ncbi.nlm.nih.gov/pubmed/27848262

Quantitative analyses of synergistic responses between cannabidiol and DNA-damaging agents on the proliferation and viability of glioblastoma and neural progenitor cells in culture.

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“Evidence suggests that the non-psychotropic cannabis-derived compound, cannabidiol (CBD), has anti-neoplastic activity in multiple types of cancers, including glioblastoma multiforme (GBM).

DNA-damaging agents remain the main standard of care treatment available for patients diagnosed with GBM.

Here we studied the anti-proliferative and cell-killing activity of CBD alone and in combination with DNA-damaging agents (temozolomide, carmustine or cisplatin) in several human GBM cell lines and in mouse primary GBM cells in cultures.

This activity was also studied in mouse neural progenitor cells (NPCs) in culture to assess for potential central nervous system (CNS) toxicity.

We found that CBD induced a dose-dependent reduction of both proliferation and viability of all cells with similar potencies, suggesting no preferential activity for cancer cells.

Hill plot analysis indicates an allosteric mechanism of action triggered by CBD in all cells.

Co-treatment regiments combining CBD and DNA-damaging agents produced synergistic anti-proliferating and cell-killing responses over a limited range of concentrations in all human GBM cell lines and mouse GBM cells as well as in mouse NPCs.

Remarkably, antagonistic responses occurred at low concentrations in select human GBM cell lines and in mouse GBM cells.

Our study suggests limited synergistic activity when combining CBD and DNA-damaging agents in treating GBM cells, along with little-to-no therapeutic window when considering NPCs.”

https://www.ncbi.nlm.nih.gov/pubmed/27821713

“Definition of antineoplastic: inhibiting or preventing the growth and spread of tumors or malignant cells”  http://www.merriam-webster.com/dictionary/antineoplastic

Clinical trials of medicinal cannabis for appetite-related symptoms from advanced cancer: a survey of preferences, attitudes and beliefs among patients willing to consider participation.

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“Australian clinical trials are planned to evaluate medicinal cannabis in a range of clinical contexts.

To explore the preferences, attitudes and beliefs of patients eligible and willing to consider participation in a clinical trial of medicinal cannabis for poor appetite and appetite-related symptoms from advanced cancer.

A cross-sectional anonymous survey was administered from July to December 2015 online and in eight adult outpatient palliative care and/or cancer services. Respondents were eligible if they were ≥18 years, had advanced cancer and poor appetite/taste problems/weight loss and might consider participating in a medicinal cannabis trial. Survey items focused on medicinal rather than recreational cannabis use and did not specify botanical or pharmaceutical products. Items asked about previous medicinal cannabis use and preferences for delivery route and invited comments and concerns.

RESULTS:

There were 204 survey respondents, of whom 26 (13%) reported prior medicinal cannabis use. Tablets/capsules were the preferred delivery mode (n = 144, 71%), followed by mouth spray (n = 84, 42%) and vaporiser (n = 83, 41%). Explanations for preferences (n = 134) most commonly cited convenience (n = 66; 49%). A total of 82% (n = 168) of respondents indicated that they had no trial-related concerns, but a small number volunteered concerns about adverse effects (n = 14) or wanted more information/advice (n = 8). Six respondents volunteered a belief that cannabis might cure cancer, while two wanted assurance of efficacy before participating in a trial.

CONCLUSION:

Justification of modes other than tablets/capsules and variable understanding about cannabis and trials will need addressing in trial-related information to optimise recruitment and ensure that consent is properly informed.”

https://www.ncbi.nlm.nih.gov/pubmed/27530738

WIN 55,212-2 Inhibits the Epithelial Mesenchymal Transition of Gastric Cancer Cells via COX-2 Signals.

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“Cannabinoids (the active components of Cannabis sativa) and their derivatives have received considerable interest due to reports that they can affect the tumor growth, migration, and metastasis.

Previous studies showed that the cannabinoid agonist WIN 55,212-2 (WIN) was associated with gastric cancer (GC) metastasis, but the mechanisms were unknown.

RESULTS:

WIN inhibited cell migration, invasion, and epithelial to mesenchymal transition (EMT) in GC. WIN treatment resulted in the downregulation of cyclooxygenase-2 (COX-2) expression and decreased the phosphorylation of AKT, and inhibited EMT in SGC7901 cells. Decreased expression of COX-2 and vimentin, and increased expression of E-cadherin, which was induced by WIN, were normalized by overexpression of AKT, suggesting that AKT mediated, at least partially, the WIN suppressed EMT of GC cells.

CONCLUSION:

WIN can inhibit the EMT of GC cells through the downregulation of COX-2.”

https://www.ncbi.nlm.nih.gov/pubmed/27802436

Cannabinoid derivatives exert a potent anti-myeloma activity both in vitro and in vivo.

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“Although hematopoietic and immune system show high levels of the cannabinoid receptor CB2, the potential effect of cannabinoids on hematologic malignancies has been poorly determined.

Here we have investigated their anti-tumor effect in multiple myeloma (MM).

We demonstrate that cannabinoids induce a selective apoptosis in MM cell lines and in primary plasma cells of MM patients, while sparing normal cells from healthy donors, including hematopoietic stem cells.

Remarkably, blockage of the CB2 receptor also inhibited cannabinoid-induced apoptosis.

Cannabinoid derivative WIN-55 enhanced the anti-myeloma activity of dexamethasone and melphalan overcoming resistance to melphalan in vitro. Finally, administration of cannabinoid WIN-55 to plasmacytoma-bearing mice significantly suppressed tumor growth in vivo.

Together, our data suggest that cannabinoids may be considered as potential therapeutic agents in the treatment of MM.”

https://www.ncbi.nlm.nih.gov/pubmed/27778331

http://www.thctotalhealthcare.com/category/multiple-myeloma/

Preclinical and Clinical Assessment of Cannabinoids as Anti-Cancer Agents.

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“Cancer is the second leading cause of death in the United States with 1.7 million new cases estimated to be diagnosed in 2016. This disease remains a formidable clinical challenge and represents a substantial financial burden to the US health care system. Therefore, research and development of novel therapeutics for the treatment of cancer is of high priority.

Cannabinoids and their derivatives have been utilized for their medicinal and therapeutic properties throughout history.

Cannabinoid activity is regulated by the endocannabinoid system (ECS), which is comprised of cannabinoid receptors, transporters, and enzymes involved in cannabinoid synthesis and breakdown.

More recently, cannabinoids have gained special attention for their role in cancer cell proliferation and death. However, many studies investigated these effects using in vitro models which may not adequately mimic tumor growth and metastasis.

As such, this article aims to review study results which evaluated effects of cannabinoids from plant, synthetic and endogenous origins on cancer development in preclinical animal models and to examine the current standing of cannabinoids that are being tested in human cancer patients.” https://www.ncbi.nlm.nih.gov/pubmed/27774065

“The studies reviewed herein indicate that cannabinoids elicit activity through cannabinoid receptor dependent and independent pathways. The evidence generated in these human studies are still informative and, when taken together with the strong in vivo animal data demonstrating anti-tumor effects of cannabinoids, offer promise for a clinical role for cannabinoids in the eradication of tumors. Hence, these investigations shed light on the role of cannabinoids on tumor growth in vivo and may ultimately pave the way for the development of novel cannabinoid therapeutics for cancer treatment.”  http://journal.frontiersin.org/article/10.3389/fphar.2016.00361/full

Targeting cannabinoid receptor-2 pathway by phenylacetylamide suppresses the proliferation of human myeloma cells through mitotic dysregulation and cytoskeleton disruption.

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“Cannabinoid receptor-2 (CB2) is expressed dominantly in the immune system, especially on plasma cells.

Cannabinergic ligands with CB2 selectivity emerge as a class of promising agents to treat CB2-expressing malignancies without psychotropic concerns.

In this study, we found that CB2 but not CB1 was highly expressed in human multiple myeloma (MM) and primary CD138+ cells.

Thus, targeting CB2 may represent an attractive approach to treat cancers of immune origin.”

https://www.ncbi.nlm.nih.gov/pubmed/25640641

The effects of cannabidiol and its synergism with bortezomib in multiple myeloma cell lines. A role for transient receptor potential vanilloid type-2.

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“Multiple myeloma (MM) is a plasma cell (PC) malignancy characterised by the accumulation of a monoclonal PC population in the bone marrow (BM).

Cannabidiol (CBD) is a non-psychoactive cannabinoid with antitumoural activities, and the transient receptor potential vanilloid type-2 (TRPV2) channel has been reported as a potential CBD receptor.

TRPV2 activation by CBD decreases proliferation and increases susceptibility to drug-induced cell death in human cancer cells.

However, no functional role has been ascribed to CBD and TRPV2 in MM. In this study, we identified the presence of heterogeneous CD138+TRPV2+ and CD138+TRPV2- PC populations in MM patients, whereas only the CD138+ TRPV2- population was present in RPMI8226 and U266 MM cell lines.

Because bortezomib (BORT) is commonly used in MM treatment, we investigated the effects of CBD and BORT in CD138+TRPV2- MM cells and in MM cell lines transfected with TRPV2 (CD138+TRPV2+).

These results showed that CBD by itself or in synergy with BORT strongly inhibited growth, arrested cell cycle progression and induced MM cells death by regulating the ERK, AKT and NF-κB pathways with major effects in TRPV2+ cells.

These data provide a rationale for using CBD to increase the activity of proteasome inhibitors in MM.”

https://www.ncbi.nlm.nih.gov/pubmed/24293211

Cannabinoids synergize with carfilzomib, reducing multiple myeloma cells viability and migration.

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“Several studies showed a potential anti-tumor role for cannabinoids, by modulating cell signaling pathways involved in cancer cell proliferation, chemo-resistance and migration.

Cannabidiol (CBD) was previously noted in multiple myeloma (MM), both alone and in synergy with the proteasome inhibitor bortezomib, to induce cell death.

In other type of human cancers, the combination of CBD with Δ9-tetrahydrocannabinol (THC) was found to act synergistically with other chemotherapeutic drugs suggesting their use in combination therapy.

In the current study, we evaluated the effects of THC alone and in combination with CBD in MM cell lines.

We found that CBD and THC, mainly in combination, were able to reduce cell viability by inducing autophagic-dependent necrosis.

Moreover, we showed that the CBD-THC combination was able to reduce MM cells migration by down-regulating expression of the chemokine receptor CXCR4 and of the CD147 plasma membrane glycoprotein.

Furthermore, since the immuno-proteasome is considered a new target in MM and also since carfilzomib (CFZ) is a new promising immuno-proteasome inhibitor that creates irreversible adducts with the β5i subunit of immuno-proteasome, we evaluated the effect of CBD and THC in regulating the expression of the β5i subunit and their effect in combination with CFZ.

Herein, we also found that the CBD and THC combination is able to reduce expression of the β5i subunit as well as to act in synergy with CFZ to increase MM cell death and inhibits cell migration.

In summary, these results proved that this combination exerts strong anti-myeloma activities.”

 https://www.ncbi.nlm.nih.gov/pubmed/27769052

Overexpression of cannabinoid receptor 1 promotes renal cell carcinoma progression.

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“Renal cell carcinoma (RCC) is a common urologic tumor with a poor prognosis.

Cannabinoid receptor 1 (CB1), which is a G protein-coupled receptor, has recently been reported to participate in the genesis and development of various cancers.

However, the exact role of CB1 in RCC is unknown. The aim of this study was to determine the role of CB1 in RCC cell lines and RCC prognosis, thus underlying its potential as a therapeutic target.

CB1 expression is functionally associated to cellular proliferation, apoptosis, and invasion ability of RCC.

Our data suggest that CB1 might be a potential target for RCC clinical therapy.”

https://www.ncbi.nlm.nih.gov/pubmed/27757850