Category Archives: Skin Cancer

Cheungsam Seed Husk Extract Reduces Skin Inflammation through Regulation of Inflammatory Mediator in TNF-α/IFN-γ-Induced HaCaT Cells

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“Cannabis contains numerous natural components and has several effects such as anticancer, anti-inflammatory and antioxidant.

Cheungsam is a variety of non-drug-type hemp, developed in Korea and is used for fiber (stem) and oil (seed). The efficacy of Cheungsam on skin is not yet known, and although there are previous studies on Cheungsam seed oil, there are no studies on Cheungsam seed husk.

In this study, we investigated the potential of Cheungsam seed husk ethanol extract (CSSH) to alleviate skin inflammation through evaluating the gene and protein expression levels of inflammatory mediators.

The results showed that CSSH reduced pro-inflammatory cytokines (IL-1β, IL-6, IL-8, MCP-1 and CXCL10) and atopic dermatitis-related cytokines (IL-4, CCL17, MDC and RANTES) in TNF-α/IFN-γ-induced HaCaT cells. Furthermore, ERK, JNK and p38 phosphorylation were decreased and p-p65, p-IκBα, NLRP3, caspase-1, p-JAK1 and p-STAT6 were suppressed after CSSH treatment. CSSH significantly increased the level of the skin barrier factors filaggrin and involucrin.

These results suggest that Cheungsam seed husk ethanol extract regulates the mechanism of skin inflammation and can be used as a new treatment for skin inflammatory diseases.”

https://pubmed.ncbi.nlm.nih.gov/38931136/

“The extract exerted anti-inflammatory and anti-atopic effects through mechanism regulation and skin barrier recovery. Therefore, Cheungsam seed husk extract may be useful for treating atopic dermatitis as well as other skin inflammatory diseases.”

https://www.mdpi.com/2223-7747/13/12/1704

Modulation of Redox and Inflammatory Signaling in Human Skin Cells Using Phytocannabinoids Applied after UVA Irradiation: In Vitro Studies

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“UVA exposure disturbs the metabolism of skin cells, often inducing oxidative stress and inflammation. Therefore, there is a need for bioactive compounds that limit such consequences without causing undesirable side effects.

The aim of this study was to analyse in vitro the effects of the phytocannabinoids cannabigerol (CBG) and cannabidiol (CBD), which differ in terms of biological effects. Furthermore, the combined use of both compounds (CBG+CBD) has been analysed in order to increase their effectiveness in human skin fibroblasts and keratinocytes protection against UVA-induced alternation.

The results obtained indicate that the effects of CBG and CBD on the redox balance might indeed be enhanced when both phytocannabinoids are applied concurrently. Those effects include a reduction in NOX activity, ROS levels, and a modification of thioredoxin-dependent antioxidant systems. The reduction in the UVA-induced lipid peroxidation and protein modification has been confirmed through lower levels of 4-HNE-protein adducts and protein carbonyl groups as well as through the recovery of collagen expression. Modification of antioxidant signalling (Nrf2/HO-1) through the administration of CBG+CBD has been proven to be associated with reduced proinflammatory signalling (NFκB/TNFα).

Differential metabolic responses of keratinocytes and fibroblasts to the effects of the UVA and phytocannabinoids have indicated possible beneficial protective and regenerative effects of the phytocannabinoids, suggesting their possible application for the purpose of limiting the harmful impact of the UVA on skin cells.”

https://pubmed.ncbi.nlm.nih.gov/38891097/

“The results presented in this manuscript indicate that the concurrent use of the two phytocannabinoids (CBG and CBD), acting as both a protective and regenerative system, may have a beneficial effect on the redox balance in human keratinocytes and skin fibroblasts, even if they were applied after UVA irradiation. The tested phytocannabinoids also counteract proinflammatory reactions, which, consequently, contribute to the development of various pathological conditions. The obtained results suggest the combined use of CBG and CBD as a potential preventive and regenerative method for skin cells, especially those damaged by UV radiation, which may be used for the purpose of both prevention and therapy.”

https://www.mdpi.com/2073-4409/13/11/965

Bipiperidinyl Derivatives of Cannabidiol Enhance Its Antiproliferative Effects in Melanoma Cells

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“Cannabis and its major cannabinoid cannabidiol (CBD) are reported to exhibit anticancer activity against skin tumors. However, the cytotoxic effects of other minor cannabinoids and synthetic CBD derivatives in melanoma are not fully elucidated. Herein, the antiproliferative activity of a panel of phytocannabinoids was screened against murine (B16F10) and human (A375) melanoma cells. CBD was the most cytotoxic natural cannabinoid with respective IC50 of 28.6 and 51.6 μM. Further assessment of the cytotoxicity of synthetic CBD derivatives in B16F10 cells identified two bipiperidinyl group-bearing derivatives (22 and 34) with enhanced cytotoxicity (IC50 = 3.1 and 8.5 μM, respectively). Furthermore, several cell death assays including flow cytometric (for apoptosis and ferroptosis) and lactate dehydrogenase (for pyroptosis) assays were used to characterize the antiproliferative activity of CBD and its bipiperidinyl derivatives. The augmented cytotoxicity of 22 and 34 in B16F10 cells was attributed to their capacity to promote apoptosis (as evidenced by increased apoptotic population). Taken together, this study supports the notion that CBD and its derivatives are promising lead compounds for cannabinoid-based interventions for melanoma management.”

https://pubmed.ncbi.nlm.nih.gov/38671925/

“In summary, a series of phytocannabinoids were evaluated for their antiproliferative effects against melanoma cells (B16F10 and A375) and CBD showed the most promising activity. In addition, chemical modifications by introducing a bipiperidinyl group in CBD resulted in a pair of CBD derivatives (22 and 34) with enhanced cytotoxicity on B16F10 and A375 cells. Furthermore, data from a panel of bioassays supported the notion that the enhanced antiproliferative effects of CBD and its bipiperidinyl derivatives were associated with their capacity to mediate programmed cell death such as apoptosis in B16F10 cells. Further studies on the anti-tumor effect of CBD and its bipiperidinyl derivatives with in vivo models are warranted to better understand their effectiveness in the potential development of melanoma management.”

https://www.mdpi.com/2076-3921/13/4/478

Evaluating the Mechanism of Cell Death in Melanoma Induced by the Cannabis Extract PHEC-66

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“Research suggests the potential of using cannabinoid-derived compounds to function as anticancer agents against melanoma cells.

Our recent study highlighted the remarkable in vitro anticancer effects of PHEC-66, an extract from Cannabis sativa, on the MM418-C1, MM329, and MM96L melanoma cell lines. However, the complete molecular mechanism behind this action remains to be elucidated.

This study aims to unravel how PHEC-66 brings about its antiproliferative impact on these cell lines, utilising diverse techniques such as real-time polymerase chain reaction (qPCR), assays to assess the inhibition of CB1 and CB2 receptors, measurement of reactive oxygen species (ROS), apoptosis assays, and fluorescence-activated cell sorting (FACS) for apoptosis and cell cycle analysis.

The outcomes obtained from this study suggest that PHEC-66 triggers apoptosis in these melanoma cell lines by increasing the expression of pro-apoptotic markers (BAX mRNA) while concurrently reducing the expression of anti-apoptotic markers (Bcl-2 mRNA). Additionally, PHEC-66 induces DNA fragmentation, halting cell progression at the G1 cell cycle checkpoint and substantially elevating intracellular ROS levels.

These findings imply that PHEC-66 might have potential as an adjuvant therapy in the treatment of malignant melanoma. However, it is essential to conduct further preclinical investigations to delve deeper into its potential and efficacy.”

https://pubmed.ncbi.nlm.nih.gov/38334660/

https://www.mdpi.com/2073-4409/13/3/268

Cannabinoids in Treating Chemotherapy-Induced Nausea and Vomiting, Cancer-Associated Pain, and Tumor Growth

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“Cannabis has been used as an herbal remedy for thousands of years, and recent research indicates promising new uses in medicine. So far, some studies have shown cannabinoids to be safe in helping mitigate some cancer-associated complications, including chemotherapy-induced nausea and vomiting, cancer-associated pain, and tumor growth.

Researchers have been particularly interested in the potential uses of cannabinoids in treating cancer due to their ability to regulate cancer-related cell cycle pathways, prompting many beneficial effects, such as tumor growth prevention, cell cycle obstruction, and cell death.

Cannabinoids have been found to affect tumors of the brain, prostate, colon and rectum, breast, uterus, cervix, thyroid, skin, pancreas, and lymph. However, the full potential of cannabinoids is yet to be understood.

This review discusses current knowledge on the promising applications of cannabinoids in treating three different side effects of cancer-chemotherapy-induced nausea and vomiting, cancer-associated pain, and tumor development.

The findings suggest that cannabinoids can be used to address some side effects of cancer and to limit the growth of tumors, though a lack of supporting clinical trials presents a challenge for use on actual patients. An additional challenge will be examining whether any of the over one hundred naturally occurring cannabinoids or dozens of synthetic compounds also exhibit useful clinical properties.

Currently, clinical trials are underway; however, no regulatory agencies have approved cannabinoid use for any cancer symptoms beyond antinausea.”

https://pubmed.ncbi.nlm.nih.gov/38203245/

https://www.mdpi.com/1422-0067/25/1/74

Cannabinoids and Their Receptors in Skin Diseases

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“The therapeutic application of cannabinoids has gained traction in recent years. Cannabinoids interact with the human endocannabinoid system in the skin. A large body of research indicates that cannabinoids could hold promise for the treatment of eczema, psoriasis, acne, pruritus, hair disorders, and skin cancer. However, most of the available data are at the preclinical stage. Comprehensive, large-scale, randomized, controlled clinical trials have not yet been fully conducted. In this article, we describe new findings in cannabinoid research and point out promising future research areas.”

https://pubmed.ncbi.nlm.nih.gov/38003712/

“In recent years, some components of cannabis, also known as marijuana, have been studied. Cannabis has been used for various purposes throughout history, including recreational, medicinal, and industrial uses. In recent years, cannabinoid components are emerging as therapeutic alternatives for patients with a variety of illnesses and conditions. In particular, their anti-inflammatory properties have piqued the interest of dermatologists [1]. Given the growing number of pre-clinical and clinical studies exploring the potential of cannabinoids to treat dermatologic conditions, we here summarize reports of cannabinoid use in dermatologic therapy.”

https://www.mdpi.com/1422-0067/24/22/16523

Rationalizing a prospective coupling effect of cannabinoids with the current pharmacotherapy for melanoma treatment

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“Melanoma is one of the leading fatal forms of cancer, yet from a treatment perspective, we have minimal control over its reoccurrence and resistance to current pharmacotherapies. The endocannabinoid system (ECS) has recently been accepted as a multifaceted homeostatic regulator, influencing various physiological processes across different biological compartments, including the skin. This review presents an overview of the pathophysiology of melanoma, current pharmacotherapy used for treatment, and the challenges associated with the different pharmacological approaches. Furthermore, it highlights the utility of cannabinoids as an additive remedy for melanoma by restoring the balance between downregulated immunomodulatory pathways and elevated inflammatory cytokines during chronic skin conditions as one of the suggested critical approaches in treating this immunogenic tumor.”

https://pubmed.ncbi.nlm.nih.gov/37920964/

“Cannabinoids, including endocannabinoids, phytocannabinoids, and synthetic agents, exert pharmacological effects on the skin by activating the specific cannabinoid receptors CB1 and CB2. Uniquely, the ECS system has been shown in vivo and in vitro to regulate the immune system through its immunomodulatory properties. They can attenuate chronic inflammatory disorders and subsequently enhance anti-tumor characteristics. In addition to their immunomodulatory effects, cannabinoids further mediate multiple anti-cancer pathways, including autophagy, apoptosis, angiogenesis, cell motility, and cell adhesion; moreover, they regulate key inflammatory processes critical to the homeostatic regulation of the tumor microenvironment. “

https://wires.onlinelibrary.wiley.com/doi/10.1002/wsbm.1633

In Vitro Antiproliferative Effect of Cannabis Extract PHEC-66 on Melanoma Cell Lines

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“Melanoma, an aggressive form of skin cancer, can be fatal if not diagnosed and treated early. Melanoma is widely recognized to resist advanced cancer treatments, including immune checkpoint inhibitors, kinase inhibitors, and chemotherapy. Numerous studies have shown that various Cannabis sativa extracts exhibit potential anticancer effects against different types of tumours both in vitro and in vivo. This study is the first to report that PHEC-66, a Cannabis sativa extract, displays antiproliferative effects against MM418-C1, MM329 and MM96L melanoma cells. Although these findings suggest that PHEC-66 has promising potential as a pharmacotherapeutic agent for melanoma treatment, further research is necessary to evaluate its safety, efficacy, and clinical applications.”

https://pubmed.ncbi.nlm.nih.gov/37887294/

“In conclusion, the results of this study demonstrate that PHEC-66 extract derived from Cannabis sativa exerts a significant cytotoxic effect on MM418-C1, MM329, and MM96L melanoma cell lines while having a lesser effect on human keratinocytes (HaCaT), human epidermal melanocytes (HEM), and normal human dermal fibroblasts (NHDF). Although the mechanism of PHEC-66’s anti-melanoma activity remains unknown, this study suggests it may induce apoptotic and necrotic cell death pathways. Further research is necessary to fully comprehend the underlying mechanisms of PHEC-66’s actions and assess its potential as a natural source of anticancer compounds.”

https://www.mdpi.com/2073-4409/12/20/2450

Differences in the phospholipid profile of melanocytes and melanoma cells irradiated with UVA and treated with cannabigerol and cannabidiol

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“UV radiation inducing mutations in melanocytes might cause melanoma. As changes in lipid composition and metabolism are associated with many types of cancer including skin cancer, we aimed to evaluate the effects of two phytocannabinoids cannabidiol (CBD) and cannabigerol (CBG), on changes in phospholipid and ceramide (CER) profiles induced by UVA irradiation in human melanocytes and melanoma. UVA radiation caused a significant up-regulation PC, PI and SM species and decrease of CERs content in both types of cells, while up-regulation of PEo was only observed in melanocytes. Exposure of UVA-irradiated melanocytes or melanoma cells to CBD and/or CBG led to significant decrease in relative content of PC, PI and SM specie; however, this effect was more pronounced in cancer cells. Interestingly, only in UVA-irradiated melanocytes and not in melanoma, PEo content was lowered after CBD treatment, while CBG led to additional up-regulation of PEo species. CBD and CBG used together caused decrease of zeta potential, inhibiting PS externalization, and different changes in relative contents of CER and SM species of irradiated and non-irradiated melanoma cells. Obtained results are quite promising due to CBD and CBG abilities to partial reverse pro-cancerogenic changes in phospholipid and CER profiles induced by UVA.”

https://pubmed.ncbi.nlm.nih.gov/37752196/

https://www.nature.com/articles/s41598-023-43363-9

Genome-Scale Metabolic Reconstruction, Non-Targeted LC-QTOF-MS Based Metabolomics Data, and Evaluation of Anticancer Activity of Cannabis sativa Leaf Extracts

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“Over the past decades, Colombia has suffered complex social problems related to illicit crops, including forced displacement, violence, and environmental damage, among other consequences for vulnerable populations. Considerable effort has been made in the regulation of illicit crops, predominantly Cannabis sativa, leading to advances such as the legalization of medical cannabis and its derivatives, the improvement of crops, and leaving an open window to the development of scientific knowledge to explore alternative uses. It is estimated that C. sativa can produce approximately 750 specialized secondary metabolites. Some of the most relevant due to their anticancer properties, besides cannabinoids, are monoterpenes, sesquiterpenoids, triterpenoids, essential oils, flavonoids, and phenolic compounds. However, despite the increase in scientific research on the subject, it is necessary to study the primary and secondary metabolism of the plant and to identify key pathways that explore its great metabolic potential. For this purpose, a genome-scale metabolic reconstruction of C. sativa is described and contextualized using LC-QTOF-MS metabolic data obtained from the leaf extract from plants grown in the region of Pesca-Boyaca, Colombia under greenhouse conditions at the Clever Leaves facility. A compartmentalized model with 2101 reactions and 1314 metabolites highlights pathways associated with fatty acid biosynthesis, steroids, and amino acids, along with the metabolism of purine, pyrimidine, glucose, starch, and sucrose. Key metabolites were identified through metabolomic data, such as neurine, cannabisativine, cannflavin A, palmitoleic acid, cannabinoids, geranylhydroquinone, and steroids. They were analyzed and integrated into the reconstruction, and their potential applications are discussed. Cytotoxicity assays revealed high anticancer activity against gastric adenocarcinoma (AGS), melanoma cells (A375), and lung carcinoma cells (A549), combined with negligible impact against healthy human skin cells.”

https://pubmed.ncbi.nlm.nih.gov/37512495/

https://www.mdpi.com/2218-1989/13/7/788