Cannabidiol Effectively Promoted Cell Death in Bladder Cancer and the Improved Intravesical Adhesion Drugs Delivery Strategy Could Be Better Used for Treatment

pharmaceutics-logo“Cannabidiol (CBD), a primary bioactive phytocannabinoid extracted from hemp, is reported to possess potent anti-tumorigenic activity in multiple cancers.

However, the effects of CBD on bladder cancer (BC) and the underlying molecular mechanisms are rarely reported.

Here, several experiments proved that CBD promoted BC cells (T24, 5637, and UM-UC-3) death.

In summary, this work demonstrates that CBD may become a novel reliable anticancer drug and the developed intravesical adhesion system is expected to turn into a potential means of BC chemotherapy drug delivery.

We believe that our study makes a significant contribution to the field because these results can be developed as a promising strategy for a safer and more efficient anticancer therapy.”

https://www.mdpi.com/1999-4923/13/9/1415/htm

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Cannabidiol Induces Apoptosis and Perturbs Mitochondrial Function in Human and Canine Glioma Cells

Frontiers in Pharmacology (@FrontPharmacol) | Twitter“Cannabidiol (CBD), the major non-psychoactive compound found in cannabis, is frequently used both as a nutraceutical and therapeutic.

Despite anecdotal evidence as an anticancer agent, little is known about the effect CBD has on cancer cells. Given the intractability and poor prognoses of brain cancers in human and veterinary medicine, we sought to characterize the in vitro cytotoxicity of CBD on human and canine gliomas.

Glioma cells treated with CBD showed a range of cytotoxicity from 4.9 to 8.2 μg/ml; canine cells appeared to be more sensitive than human.

These results demonstrate the cytotoxic nature of CBD in human and canine glioma cells and suggest a mechanism of action involving dysregulation of calcium homeostasis and mitochondrial activity.”

https://pubmed.ncbi.nlm.nih.gov/34456736/

“In this present study, we demonstrate that highly purified CBD isolate reduced proliferation and induced caspase-mediated cell death, suggestive of apoptosis, in both canine glioma cell lines SDT3G and J3TBG as well as the human glioma cell lines U87MG and U373MG Uppsala. The growing body of knowledge of the pharmacology, anticancer effects, and other therapeutically relevant properties of cannabidiol reveal the exciting potential of CBD as a potential clinical therapeutic.”

https://www.frontiersin.org/articles/10.3389/fphar.2021.725136/full

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The Pathophysiology and the Therapeutic Potential of Cannabinoids in Prostate Cancer

cancers-logo“Prostate cancer is the second most frequently occurring cancer diagnosed among males. Recent preclinical evidence implicates cannabinoids as powerful regulators of cell growth and differentiation. In this review, we focused on studies that demonstrated anticancer effects of cannabinoids and their possible mechanisms of action in prostate cancer. Besides the palliative effects of cannabinoids, research from the past two decades has demonstrated their promising potential as antitumor agents in a wide variety of cancers. This analysis may provide pharmacological insights into the selection of specific cannabinoids for the development of antitumor drugs for the treatment of prostate cancer.”

https://pubmed.ncbi.nlm.nih.gov/34439262/

“Prostate cancer, after lung cancer, is the leading cause of death among men. Although the pathophysiological mechanisms and the etiological factors of prostate cancer development are still poorly understood, there are several factors associated with the risk of developing the disease such as age, family history, lifestyle-related factors (e.g., smoking, diet), and testosterone levels. Cannabinoids are an emerging class of pharmacological molecules that may exert their therapeutic effect against different cancers, including those from the prostate. Several studies have shown that various agonists are able to target cannabinoid receptors exhibited on prostate cancer cells.”

https://www.mdpi.com/2072-6694/13/16/4107

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Therapeutic Potential of Neoechinulins and Their Derivatives: An Overview of the Molecular Mechanisms Behind Pharmacological Activities

Neuroenergetics, Nutrition and Brain Health | Authors“Neoechinulins are diketopiperazine type indole alkaloids that demonstrate radical scavenging, anti-inflammatory, antiviral, anti-neurodegenerative, neurotrophic factor-like, anticancer, pro-apoptotic, and anti-apoptotic properties.

An array of neoechinulins such as neoechinulins A-E, isoechinulins A-C, cryptoechunilin have been isolated from various fungal sources like Aspergillus sp., Xylaria euglossa, Eurotium cristatum, Microsporum sp., etc. Besides, neoechinulin derivatives or stereoisomers were also obtained from diverse non-fungal sources viz. Tinospora sagittata, Opuntia dillenii, Cyrtomium fortunei, Cannabis sativa, and so on.

The main purpose of this review is to provide update information on neoechinulins and their analogues about the molecular mechanisms of the pharmacological action and possible future research. The recent data from this review can be used to create a basis for the discovery of new neoechinulin-based drugs and their analogues in the near future.

The online databases PubMed, Science and Google scholar were researched for the selection and collection of data from the available literature on neoechinulins, their natural sources and their pharmacological properties.

The published books on this topic were also analysed. In vitro and in vivo assays have established the potential of neoechinulin A as a promising anticancer and anti-neuroinflammatory lead molecule. Neoechinulin B was also identified as a potential antiviral drug against hepatitis C virus.

Toxicological and clinical trials are needed in the future to improve the phyto-pharmacological profile of neoquinolines. From the analysis of the literature, we found that neoechinulins and their derivatives have special biological potential.”

https://pubmed.ncbi.nlm.nih.gov/34336908/

“In the future, neoquinolines may be introduced into functional foods or dietary compounds (nutraceuticals) that benefit human health by preventing or treating diseases, or by correcting metabolic disorders, or by preventing the progression or recurrence of a pathological situation.”

https://www.frontiersin.org/articles/10.3389/fnut.2021.664197/full

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Myrcene-What Are the Potential Health Benefits of This Flavouring and Aroma Agent?

Neuroenergetics, Nutrition and Brain Health | Authors“Myrcene (β-myrcene) is an abundant monoterpene which occurs as a major constituent in many plant species, including hops and cannabis. It is a popular flavouring and aroma agent (food additive) used in the manufacture of food and beverages. This review aims to report on the occurrence, biological and toxicological profile of β-myrcene. The main reported biological properties of β-myrcene-anxiolytic, antioxidant, anti-ageing, anti-inflammatory, analgesic properties-are discussed, with the mechanisms of activity. Here we also discuss recent data regarding the safety of β-myrcene. Overall, β-myrcene has shown promising health benefits in many animal studies. However, studies conducted in humans is lacking. In the future, there is potential for the formulation and production of non-alcoholic beers, functional foods and drinks, and cannabis extracts (low in THC) rich in β-myrcene.”

https://pubmed.ncbi.nlm.nih.gov/34350208/

“β-Myrcene characteristically gives cannabis strains a mildly sweet flavour profile and provides scent notes that are spicy, earthy and musky. Cannabis strains which contain high concentrations of myrcene (>0.5% myrcene), are likely to induce sedative qualities (“couch-lock effect”), which are classically attributed to Cannabis indica Lam (a synonym of C. sativa L.) strains. On the other hand, strains low in β-myrcene (<0.5%) are likely to induce a more energic “high”.β-Myrcene reported biological activities include analgesic, sedative, antidiabetic, antioxidant, anti-inflammatory, antibacterial, and anticancer effects.”

https://www.frontiersin.org/articles/10.3389/fnut.2021.699666/full

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A Novel Mechanism of Cannabidiol in Suppressing Hepatocellular Carcinoma by Inducing GSDME Dependent Pyroptosis

Frontiers in Cell and Developmental Biology - Institut de Myologie“Cannabidiol (CBD), a phytochemical derived from Cannabis sativa L., has been demonstrated to exhibit promising anti-tumor properties in multiple cancer types. However, the effects of CBD on hepatocellular carcinoma (HCC) cells remain unknown. We have shown that CBD effectively suppresses HCC cell growth in vivo and in vitro, and induced HCC cell pyroptosis in a caspase-3/GSDME-dependent manner. We further demonstrated that accumulation of integrative stress response (ISR) and mitochondrial stress may contribute to the initiation of pyroptotic signaling by CBD. Simultaneously, CBD can repress aerobic glycolysis through modulation of the ATF4-IGFBP1-Akt axis, due to the depletion of ATP and crucial intermediate metabolites. Collectively, these observations indicate that CBD could be considered as a potential compound for HCC therapy.”

https://pubmed.ncbi.nlm.nih.gov/34350183/

“Hepatocellular carcinoma (HCC) is an extremely malignant cancer, accounting for almost 95% of primary liver cancer cases. Cannabidiol (CBD), a phytochemical derived from Cannabis sativa L., has been shown to have anti-tumor activity and to be a potential compound for tumor therapy. Previous studies have demonstrated that CBD treatment could effectively induce cell apoptosis in tumor cells. In this study, we have shown that CBD can effectively suppress HCC cell growth both in vitro and in vivo, which was similar to the anti-tumor activity of CBD observed in other cancer types. In summary, a mechanistic model of CBD anti-tumor activity in HCC cell pyroptosis and growth was demonstrated. All the observations described herein reveal a novel mechanism of the anti-tumor activity of CBD in HCC cells, suggesting that CBD could be considered as a promising compound for HCC therapy.”

https://www.frontiersin.org/articles/10.3389/fcell.2021.697832/full

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Combination therapy with cannabidiol and chemotherapeutics in canine urothelial carcinoma cells

“Background: Canine urothelial carcinoma is the most common form of canine bladder cancer. Treatment with chemotherapy has variable response rates leading to most dogs succumbing to their disease within a year. Cannabidiol is an emerging treatment within the field of oncology. In reported in vivo studies, cannabidiol has induced apoptosis, reduced cell migration, and acted as a chemotherapy sensitizer in various human tumor types. The aim of this study was to characterize the effects of cannabidiol on canine urothelial carcinoma cell viability and apoptosis as both a single agent and in combination with chemotherapy in vitro.

Results: Cannabidiol reduced cell viability and induced apoptosis in canine urothelial cells as determined by crystal violet viability assay and annexin V/propidium iodide flow cytometry. Furthermore, combinations of cannabidiol with mitoxantrone and vinblastine chemotherapy yielded significantly reduced cell viability and increased apoptosis compared to single agent treatment alone. The drug interactions were deemed synergistic based on combination index calculations. Conversely, the combination of cannabidiol and carboplatin did not result in decreased cell viability and increased apoptosis compared to single agent treatment. Combination index calculations suggested an antagonistic interaction between these drugs. Finally, the combination of the non-steroidal anti-inflammatory drug piroxicam with cannabidiol did not significantly affect cell viability, although, some cell lines demonstrated decreased cell viability when mitoxantrone was combined with piroxicam.

Conclusions: Cannabidiol showed promising results as a single agent or in combination with mitoxantrone and vinblastine for treatment of canine urothelial carcinoma cells. Further studies are justified to investigate whether these results are translatable in vivo.”

https://pubmed.ncbi.nlm.nih.gov/34352013/

“Cannabidiol (CBD) is a phytocannabinoid derived from the Cannabis sativa plant with well-documented analgesic, anti-inflammatory, and anxiolytic effects. This study determined that CBD treatment reduced viability and induced cell death in canine urothelial carcinoma cells in vitro. Taken together, these results suggest that CBD may be a potential treatment for use in combination with chemotherapeutic agents to improve canine UC carcinoma response rates and survival.”

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0255591

 

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The Pharmacological Effects of Plant-Derived versus Synthetic Cannabidiol in Human Cell Lines

/WebMaterial/ShowPic/1344608“Introduction: Cannabidiol (CBD) can be isolated from Cannabis sativa L. or synthetically produced. The aim of this study was to compare the in vitro effects of purified natural and synthetic CBD to establish any pharmacological differences or superiority between sources. 

Conclusion: Our results suggest that there is no pharmacological difference in vitro in the antiproliferative, anti-inflammatory, or permeability effects of purified natural versus synthetic CBD. The purity and reliability of CBD samples, as well as the ultimate pharmaceutical preparation, should all be considered above the starting source of CBD in the development of new CBD medicines.

This study demonstrates for the first time that the anticancer, neuroprotective, and intestinal barrier protective properties of purified CBD are similar regardless of the source from which CBD is derived. From a pharmacological perspective, where a molecular target is implicated (i.e., 5HT1A in stroke and CB1 in gut permeability), the effects of CBD were similar. This suggests that any beneficial effects that could be achieved in a clinical setting for purified CBD are likely to be similar at a pharmacodynamic level.”

https://www.karger.com/Article/FullText/517120

“Study finds no in-vitro pharmacological difference in the antiproliferative, anti-inflammatory, or permeability effects of purified natural versus synthetic CBD”

https://www.streetinsider.com/Globe+Newswire/Artelo+Biosciences+Announces+Publication+of+Study+Results+Comparing+the+Pharmacological+Effects+of+Plant-Derived+Versus+Synthetic+Cannabidiol+in+Human+Cell+Lines/18767297.html

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Cannabidiol Loaded Extracellular Vesicles Sensitize Triple-Negative Breast Cancer to Doxorubicin in both in-vitro and in vivo Models Running Title: Formulation and anti-cancer potential of CBD loaded hUCMSC-derived Extracellular Vesicles in TNBC

International Journal of Pharmaceutics“Extracellular Vesicles (EVs) were isolated from human umbilical cord mesenchymal stem cells (hUCMSCs) and were further encapsulated with cannabidiol (CBD) through sonication method (CBD EVs). CBD EVs displayed an average particle size of 114.1±1.02 nm, zeta potential of -30.26±0.12 mV, entrapment efficiency of 92.3±2.21% and stability for several months at 4 °C. CBD release from the EVs was observed as 50.74±2.44% and 53.99±1.4% at pH 6.8 and pH 7.4, respectively after 48 h. Ourin-vitrostudies demonstrated that CBD either alone or in EVs form significantly sensitized MDA-MB-231 cells to doxorubicin (DOX) (*P<0.05). Flow cytometry and migration studies revealed that CBD EVs either alone or in combination with DOX induced G1 phase cell cycle arrest and decreased migration of MDA-MB-231 cells, respectively. CBD EVs and DOX combination significantly reduced tumor burden (***P<0.001) in MDA-MB-231 xenograft tumor model. Western blotting and immunocytochemical analysis demonstrated that CBD EVs and DOX combination decreased the expression of proteins involved in inflammation, metastasis and increased the expression of proteins involved in apoptosis. CBD EVs and DOX combination will have profound clinical significance in not only decreasing the side effects but also increasing the therapeutic efficacy of DOX in TNBC.”

https://pubmed.ncbi.nlm.nih.gov/34324983/

https://www.sciencedirect.com/science/article/abs/pii/S0378517321007493?via%3Dihub

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KY Hemp-induced Modulation of Ovarian Cancer Cell Metastasis

“Our laboratory is interested in searching for a new plant-based therapeutics to treat ovarian cancer.

We are interested in studying anti-cancer effects of KY grown hemp as a potential candidate drug.

Marijuana and hemp belong to the same genus and species. However, they are different in cannabidiol (CBD) and tetrahydrocannabinol (THC) content.

Both CBD and THC are therapeutically beneficial. Hemp is harmless and non-addictive.

Major objective of this study is to investigate whether KY hemp extract can modulate the metastasis of ovarian cancer.

Based on the data here we conclude that KY hemp has significant anti-metastatic properties against ovarian cancer.”

https://faseb.onlinelibrary.wiley.com/doi/abs/10.1096/fasebj.2018.32.1_supplement.667.7

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