Category Archives: Melanoma

Impact of Cannabinoid Compounds on Skin Cancer

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“Drugs targeting the endocannabinoid system are of interest as potential systemic chemotherapeutic treatments and for palliative care in cancer.

In this context, cannabinoid compounds have been successfully tested as a systemic therapeutic option in preclinical models over the past decades. Recent findings have suggested an essential function of the endocannabinoid system in the homeostasis of various skin functions and indicated that cannabinoids could also be considered for the treatment and prophylaxis of tumour diseases of the skin.

Cannabinoids have been shown to exert their anticarcinogenic effects at different levels of skin cancer progression, such as inhibition of tumour growth, proliferation, invasion and angiogenesis, as well as inducing apoptosis and autophagy. This review provides an insight into the current literature on cannabinoid compounds as potential pharmaceuticals for the treatment of melanoma and squamous cell carcinoma.”

https://pubmed.ncbi.nlm.nih.gov/35406541/

“Recent research has suggested that the endocannabinoid system offers several pharmacotherapeutic targets for drug administration as new options for the treatment and prophylaxis of skin cancer. This review focused on the anticarcinogenic mechanisms of cannabinoids at the different levels of skin cancer progression, such as inhibition of tumour growth, proliferation, invasion and angiogenesis, as well as inducing apoptosis and autophagy.”

https://www.mdpi.com/2072-6694/14/7/1769


Plant-derived cannabinoids as anticancer agents

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“Substantial preclinical evidence demonstrates the antiproliferative, cytotoxic, and antimetastatic properties of plant-derived cannabinoids (phytocannabinoids) such as cannabidiol and tetrahydrocannabinol. The cumulative body of research into the intracellular mechanisms and phenotypic effects of these compounds supports a logical, judicious progression to large-scale phase II/III clinical trials in certain cancer types to truly assess the efficacy of phytocannabinoids as anticancer agents.”

https://pubmed.ncbi.nlm.nih.gov/35260379/

Cannabinoids as anticancer drugs: current status of preclinical research

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“Drugs that target the endocannabinoid system are of interest as pharmacological options to combat cancer and to improve the life quality of cancer patients. From this perspective, cannabinoid compounds have been successfully tested as a systemic therapeutic option in a number of preclinical models over the past decades. As a result of these efforts, a large body of data suggests that the anticancer effects of cannabinoids are exerted at multiple levels of tumour progression via different signal transduction mechanisms. Accordingly, there is considerable evidence for cannabinoid-mediated inhibition of tumour cell proliferation, tumour invasion and metastasis, angiogenesis and chemoresistance, as well as induction of apoptosis and autophagy. Further studies showed that cannabinoids could be potential combination partners for established chemotherapeutic agents or other therapeutic interventions in cancer treatment. Research in recent years has yielded several compounds that exert promising effects on tumour cells and tissues in addition to the psychoactive Δ9-tetrahydrocannabinol, such as the non-psychoactive phytocannabinoid cannabidiol and inhibitors of endocannabinoid degradation. This review provides an up-to-date overview of the potential of cannabinoids as inhibitors of tumour growth and spread as demonstrated in preclinical studies.”

https://pubmed.ncbi.nlm.nih.gov/35277658/

Cannabidiol and Other Phytocannabinoids as Cancer Therapeutics

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“Preclinical models provided ample evidence that cannabinoids are cytotoxic against cancer cells. Among the best studied phytocannabinoids, cannabidiol (CBD) is most promising for the treatment of cancer as it lacks the psychotomimetic properties of delta-9-tetrahydrocannabinol (THC). In vitro studies and animal experiments point to a concentration- (dose-)dependent anticancer effect. The effectiveness of pure compounds versus extracts is the subject of an ongoing debate. Actual results demonstrate that CBD-rich hemp extracts must be distinguished from THC-rich cannabis preparations. Whereas pure CBD was superior to CBD-rich extracts in most in vitro experiments, the opposite was observed for pure THC and THC-rich extracts, although exceptions were noted. The cytotoxic effects of CBD, THC and extracts seem to depend not only on the nature of cannabinoids and the presence of other phytochemicals but also largely on the nature of cell lines and test conditions. Neither CBD nor THC are universally efficacious in reducing cancer cell viability. The combination of pure cannabinoids may have advantages over single agents, although the optimal ratio seems to depend on the nature of cancer cells; the existence of a ‘one size fits all’ ratio is very unlikely. As cannabinoids interfere with the endocannabinoid system (ECS), a better understanding of the circadian rhythmicity of the ECS, particularly endocannabinoids and receptors, as well as of the rhythmicity of biological processes related to the growth of cancer cells, could enhance the efficacy of a therapy with cannabinoids by optimization of the timing of the administration, as has already been reported for some of the canonical chemotherapeutics. Theoretically, a CBD dose administered at noon could increase the peak of anandamide and therefore the effects triggered by this agent. Despite the abundance of preclinical articles published over the last 2 decades, well-designed controlled clinical trials on CBD in cancer are still missing. The number of observations in cancer patients, paired with the anticancer activity repeatedly reported in preclinical in vitro and in vivo studies warrants serious scientific exploration moving forward.”

https://pubmed.ncbi.nlm.nih.gov/35244889/

Cannabis as a potential compound against various malignancies, legal aspects, advancement by exploiting nanotechnology and clinical trials

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“Various preclinical and clinical studies exhibited the potential of cannabis against various diseases, including cancer and related pain. Subsequently, many efforts have been made to establish and develop cannabis-related products and make them available as prescription products. Moreover, FDA has already approved some cannabis-related products, and more advancement in this aspect is still going on. However, the approved product of cannabis is in oral dosage form, which exerts various limitations to achieve maximum therapeutic effects. A considerable translation is on a hike to improve bioavailability, and ultimately, the therapeutic efficacy of cannabis by the employment of nanotechnology. Besides the well-known psychotropic effects of cannabis upon the use at high doses, literature has also shown the importance of cannabis and its constituents in minimising the lethality of cancer in the preclinical models. This review discusses the history of cannabis, its legal aspect, safety profile, the mechanism by which cannabis combats with cancer, and the advancement of clinical therapy by exploiting nanotechnology. A brief discussion related to the role of cannabinoid in various cancers has also been incorporated. Lastly, the information regarding completed and ongoing trials have also been elaborated.”

https://pubmed.ncbi.nlm.nih.gov/35321629/

Cannabinoids and their derivatives in struggle against melanoma

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SpringerLink“Melanoma is one of the most aggressive malignances in human. Recently developed therapies improved overall survival rate, however, the treatment of melanoma still remains a challenging issue.

This review attempts to summarize recent advances in studies on cannabinoids used in the setting of melanoma treatment.

Conclusions after analysis of available data suggest that cannabinoids limit number of metastasis, and reduce growth of melanoma. The findings indicate that cannabinoids induce apoptosis, necrosis, autophagy, cell cycle arrest and exert significant interactions with tumor microenvironment.

Cannabinoids should be rather considered as a part of multi-targeted anti-tumor therapy instead of being standalone agent. Moreover, cannabinoids are likely to improve quality of life in patients with cancer, due to different supportive effects, like analgesia and/or anti-emetic effects.

In this review, it was pointed out that cannabinoids may be potentially useful in the melanoma therapy. Nevertheless, due to limited amount of data, great variety of cannabinoids available and lack of clinical trials, further studies are required to determine an exact role of cannabinoids in the treatment of melanoma.”

https://pubmed.ncbi.nlm.nih.gov/34264513/

“The endocannabinoid system is dysregulated in numerous pathological conditions, including malignancies. Recently, cannabinoids have received increasing amount of interest in the setting of treatment of various cancers.  Cannabinoids seem to be promising agents in the setting of melanoma treatment. In the case of melanoma, most important actions of cannabinoids described so far are decrease of cells viability by increase of apoptosis, necrosis and cell cycle arrest. Moreover, cannabinoids slow down disease progress by reduction of metastasis and tumor vascularization. Due to large variety of cannabinoids, there are many potential derivatives, which may be found useful in the therapy of melanoma.”

https://link.springer.com/article/10.1007%2Fs43440-021-00308-1

Cannabinoid Receptor Type-2 in B Cells Is Associated with Tumor Immunity in Melanoma

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cancers-logo“Agents targeting the endocannabinoid system (ECS) have gained attention as potential cancer treatments. Given recent evidence that cannabinoid receptor 2 (CB2R) regulates lymphocyte development and inflammation, we performed studies on CB2R in the immune response against melanoma. Analysis of The Cancer Genome Atlas (TCGA) data revealed a strong positive correlation between CB2R expression and survival, as well as B cell infiltration in human melanoma. In a murine melanoma model, CB2R expression reduced the growth of melanoma as well as the B cell frequencies in the tumor microenvironment (TME), compared to CB2R-deficient mice. In depth analysis of tumor-infiltrating B cells using single-cell RNA sequencing suggested a less differentiated phenotype in tumors from Cb2r-/- mice. Thus, in this study, we demonstrate for the first time a protective, B cell-mediated role of CB2R in melanoma. This gained insight might assist in the development of novel, CB2R-targeted cancer therapies.”

https://pubmed.ncbi.nlm.nih.gov/33923757/

“In this study we investigated the role of cannabinoid receptor 2 (CB2R) on immune cells in melanoma and found significantly improved overall survival in patients with high intra-tumoral CB2R gene expression. In human melanoma, CB2R is predominantly expressed in B cells, as shown using a previously published single-cell RNA sequencing (scRNA-seq) dataset and by performing RNAscope. In a murine melanoma model, tumor growth was enhanced in CB2R-deficient mice. In-depth analysis of tumor-infiltrating lymphocytes using scRNA-seq showed less differentiated B cells in CB2R-deficient tumors, favoring the induction of regulatory T cells (Treg) and an immunosuppressive tumor microenvironment. Taken together, these data indicate a central role of CB2R on B cells in regulating tumor immunity. These results contribute to the understanding of the role of CB2R in tumor immunity and facilitate the development of new CB2R-targeted anti-cancer drugs.”

https://www.mdpi.com/2072-6694/13/8/1934

Effects of cannabidiol (CBD) on the inhibition of melanoma cells in vitro

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Journal of Immunoassay and Immunochemistry: Vol 41, No 5 “Cannabidiol (CBD) is one of the most popular emerging plant extracts that is being investigated for its wide range of potential health benefits.

This experiment tests how B16 mice melanoma cells, are affected by four different concentrations (0.2 mg/mL, 0.04 mg/mL, 0.008 mg/mL and 0.0016 mg/mL) of 99% CBD oil.

The results of this experiment demonstrate that CBD significantly inhibited melanoma cell growth in-vitro at 0.2 mg/mL and 0.04 mg/mL.

This shows that CBD has the potential to inhibit melanoma cell growth in vertebrates, namely mice.”

https://pubmed.ncbi.nlm.nih.gov/33428525/

 

Effects of standardized Cannabis sativa extract and ionizing radiation in melanoma cells in vitro

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Journal of Cancer Research and Therapeutics “Melanoma causes the highest number of skin cancer-related deaths worldwide. New treatment methods are essential for the management of this life-threatening disease.

Aims: In this study, we investigated the efficacy of a standardized Cannabis sativa extract alone or in combination with single radiation dose (6 Gy) in B16F10 mouse melanoma cells in an extract dose-dependent manner.

Results: Administration of the extract alone or alongside radiation substantially inhibited melanoma cell viability and proliferation in the extract dose response-dependent manner. The inhibition of melanoma cell viability was paralleled by an increase in necrosis but not apoptosis when melanoma cells were treated with the extract alone. Radiation alone did not have any antiproliferative effects, and radiation also did not synergize antiproliferative effects of the extract when the extract and radiation were combined.

Conclusion: Our data suggest that C. sativa extract may have significant health and physiological implications for the treatment of melanoma. The results of this study also indicate that B16F10 mouse melanoma cells are radioresistant. Taken together, these findings may lead to the identification of new therapeutic strategy for the management of melanoma.”

https://pubmed.ncbi.nlm.nih.gov/33342819/

“This study provides the first evidence of antitumor effects of C. sativa extract, when administered alone or in combination with radiation, to mouse melanoma cells in vitro. Our results may verify the value of C. sativa extract for the treatment of melanoma and may complement the therapeutic profile of C. sativa extracts administration in the future.”

https://www.cancerjournal.net/article.asp?issn=0973-1482;year=2020;volume=16;issue=6;spage=1495;epage=1499;aulast=Naderi

Therapeutic application of cannabidiol on UVA and UVB irradiated rat skin. A proteomic study

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Journal of Pharmaceutical and Biomedical Analysis “UV phototherapy used in chronic skin diseases causes redox imbalance and pro-inflammatory reactions, especially in the case of unchanged skin cells.

To prevent the harmful effects of UV radiation, cannabidiol (CBD) has been used, which has antioxidant and anti-inflammatory properties. Therefore, the aim of this study was to evaluate the effect of CBD on the metabolism of skin keratinocytes in nude rats exposed to UVA/UVB radiation using a proteomic approach.

The results obtained with SDS-PAGE/nanoHPLC/QexactiveOrbiTrap show that exposure of rat’s skin to UVA/UVB radiation, as well as the action of CBD, significantly modified the expression of proteins involved in inflammation, redox balance and apoptosis.

UVA/UVB radiation significantly increased the expression and biological effectiveness of the nuclear factor associated with erythroid factor 2 (Nrf2) and cytoprotective proteins being products of its transcriptional activity, including superoxide dismutase (Cu,Zn-SOD) and the inflammatory response (nuclear receptor coactivator-3 and paralemmin-3), while CBD treatment counteracted and partially eliminated these changes.

Moreover, cannabidiol reversed changes in the UV-induced apoptotic pathways by modifying anti-apoptotic and pro-apoptotic factors (apoptosis regulator Bcl-2 and transforming growth factor-β).

The results show that CBD maintains keratinocyte proteostasis and therefore could be suggested as a protective measure in the prevention of UV-induced metabolic changes in epidermal keratinocytes.”

https://pubmed.ncbi.nlm.nih.gov/33086172/

“In summary, UVA and UVB radiation affect the proteomic profile of keratinocytes of healthy rat skin in different ways. Both types of radiation change the level of proteins involved in the regulation of cellular redox balance, inflammation, and apoptosis. In contrast, topical application of CBD to rat skin, when exposed to UV radiation, helps normalize the expression of keratinocyte proteins that are metabolically relevant by modeling their biosynthesis and degradation. Thus, CBD can maintain the proteostasis of keratinocytes. Because UV therapy is a part of the treatment of skin diseases, e.g. psoriasis, the use of CBD on unchanged skin may be suggested as a protective factor to reduce the metabolic changes caused by UV radiation in unchanged keratinocytes. This suggestion is particularly important when the beneficial effect of cannabidiol on psoriasis-induced skin lesions has recently also been confirmed.”

https://www.sciencedirect.com/science/article/pii/S0731708520315429?via%3Dihub