Category Archives: Cancer

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

Cannabidiol Inhibits the Proliferation and Invasiveness of Prostate Cancer Cells

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“Prostate cancer is the fifth leading cause of cancer death in men, responsible for over 375,000 deaths in 2020. Novel therapeutic strategies are needed to improve outcomes. Cannabinoids, chemical components of the cannabis plant, are a possible solution.

Preclinical evidence demonstrates that cannabinoids can modulate several cancer hallmarks of many tumor types. However, the therapeutic potential of cannabinoids in prostate cancer has not yet been fully explored. The aim of this study was to investigate the antiproliferative and anti-invasive properties of cannabidiol (CBD) in prostate cancer cells in vitro.

CBD inhibited cell viability and proliferation, accompanied by reduced expression of key cell cycle proteins, specifically cyclin D3 and cyclin-dependent kinases CDK2, CDK4, and CDK1, and inhibition of AKT phosphorylation. The effects of CBD on cell viability were not blocked by cannabinoid receptor antagonists, a transient receptor potential vanilloid 1 (TRPV1) channel blocker, or an agonist of the G-protein-coupled receptor GPR55, suggesting that CBD acts independently of these targets in prostate cancer cells. Furthermore, CBD reduced the invasiveness of highly metastatic PC-3 cells and increased protein expression of E-cadherin.

The ability of CBD to inhibit prostate cancer cell proliferation and invasiveness suggests that CBD may have potential as a future chemotherapeutic agent.”

https://pubmed.ncbi.nlm.nih.gov/37703852/

“These findings suggest that CBD has potential as a future chemotherapeutic agent for prostate cancer.”

https://pubs.acs.org/doi/10.1021/acs.jnatprod.3c00363

CBD Inhibits In Vivo Development of Human Breast Cancer Tumors

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“Inflammation is a critical component of cancer development. Previously, we showed in vitro that IL-1β treatment of non-invasive human breast cancer MCF-7 cells promoted their transition to a malignant phenotype (6D cells). This epithelial-mesenchymal transition was reverted by exposure to cannabidiol (CBD).

We show in a murine model that subcutaneous inoculation of 6D cells induced formation and development of tumors, the cells of which keep traits of malignancy. These processes were interrupted by administration of CBD under two schemes: therapeutic and prophylactic. In the therapeutic scheme, 6D cells inoculated mice developed tumors that reached a mean volume of 540 mm3 at 45 days, while 50% of CBD-treated mice showed gradual resorption of tumors. In the prophylactic scheme, mice were pre-treated for 15 days with CBD before cells inoculation. The tumors formed remained small and were eliminated under continuous CBD treatment in 66% of the animals. Histological and molecular characterization of tumors, from both schemes, revealed that CBD-treated cells decreased the expression of malignancy markers and show traits related with apoptosis.

These results confirm that in vivo CBD blocks development of breast cancer tumors formed by cells induced to malignancy by IL-1β, endorsing its therapeutic potential for cancer treatment.”

https://pubmed.ncbi.nlm.nih.gov/37686042/

“In conclusion, the present study shows that CBD, properly administered, can effectively block development of human breast cancer tumors in vivo, without causing adverse effects, by regulating in the tumor cells the expression of malignant traits and bearing characteristics of a possible route via apoptosis, both favorable attributes for an anticancer drug.”

https://www.mdpi.com/1422-0067/24/17/13235

Rimonabant and Cannabidiol Rewrite the Interactions between Breast Cancer Cells and Tumor Microenvironment

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“The spread of breast cancer to distant sites is the major cause of death in breast cancer patients. Increasing evidence supports the role of the tumor microenvironment (TME) in breast cancers, and its pathologic assessment has become a diagnostic and therapeutic tool. In the TME, a bidirectional interplay between tumor and stromal cells occurs, both at the primary and metastatic site. Hundreds of molecules, including cytokines, chemokines, and growth factors, contribute to this fine interaction to promote tumor spreading.

Here, we investigated the effects of Rimonabant and Cannabidiol, known for their antitumor activity, on reprogramming the breast TME.

Both compounds directly affect the activity of several pathways involved in breast cancer progression. To mimic tumor-stroma interactions during breast-to-lung metastasis, we investigated the effect of the compounds on growth factor secretion from metastatic breast cancer cells and normal and activated lung fibroblasts.

In this setting, we demonstrated the anti-metastatic potential of the two compounds, and the membrane array analyses highlighted their ability to alter the release of factors involved in the autocrine and paracrine regulation of tumor proliferation, angiogenesis, and immune reprogramming.

The results enforce the antitumor potential of Rimonabant and Cannabidiol, providing a novel potential tool for breast cancer TME management.”

https://pubmed.ncbi.nlm.nih.gov/37686233/

https://www.mdpi.com/1422-0067/24/17/13427

Mechanisms Involved in the Therapeutic Effect of Cannabinoid Compounds on Gliomas: A Review with Experimental Approach

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“Introduction: Brain tumors have high morbidity and mortality rates, accounting for 1.4% of all cancers. Gliomas are the most common primary brain tumors in adults. Currently, several thera-peutic approaches are used; however, they are associated with side effects that affect pa-tients’quality of life. Therefore, further studies are needed to develop novel therapeutic protocols with a more favorable side effect profile. In this context, cannabinoid compounds may serve as potential alternatives.

Objective: This study aimed to review the key enzymatic targets involved in glioma pathophysi-ology and evaluate the potential interaction of these targets with four cannabinoid derivatives through molecular docking simulations.

Methods: Molecular docking simulations were performed using four cannabinoid compounds and six molecular targets associated with glioma pathophysiology.

Results: Encouraging interactions between the selected enzymes and glioma-related targets were observed, suggesting their potential activity through these pathways. In particular, cannabigerol showed promising interactions with epidermal growth factor receptors and phosphatidylinositol 3-kinase, while Δ-9-tetrahydrocannabinol showed remarkable interactions with telomerase reverse transcriptase.

Conclusion: The evaluated compounds exhibited favorable interactions with the analyzed enzy-matic targets, thus representing potential candidates for further in vitro and in vivo studies.”

https://pubmed.ncbi.nlm.nih.gov/37649287/

https://www.eurekaselect.com/article/134162

Cannabinoids for symptom management in children with cancer: A systematic review and meta-analysis

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“Background: Despite the widespread use of medical cannabis, little is known regarding the safety, efficacy, and dosing of cannabis products in children with cancer. The objective of this study was to systematically appraise the existing published literature for the use of cannabis products in children with cancer.

Methods: This systematic review, registered with the International Prospective Register of Systematic Reviews (CRD42020187433), searched four databases: MEDLINE, Embase, PsycINFO, and the Cochrane Library. Abstracts and full texts were screened in duplicate. Data on types of cannabis products, doses, formulations, frequencies, routes of administration, indications, and clinical and demographic details as well as reported efficacy outcomes were extracted. Data on cannabinoid-related adverse events were also summarized.

Results: Out of 34,611 identified citations, 19 unique studies with a total of 1927 participants with cancer were included: eight retrospective chart reviews, seven randomized controlled trials, two open-label studies, and two case reports. The included studies reported the use of various cannabis products for the management of symptoms. Cannabinoids were commonly used for the management of chemotherapy-induced nausea and vomiting (11 of 19 [58%]). In controlled studies, somnolence, dizziness, dry mouth, and withdrawal due to adverse events were more commonly associated with the use of cannabinoids. Across all included studies, no serious cannabis-related adverse events were reported.

Conclusions: Although there is evidence to support the use of cannabis for symptom management, in children with cancer, there is a lack of rigorous evidence to inform the dosing, safety, and efficacy of cannabinoids. Because of the increasing interest in using cannabis, there is an urgent need for more research on medical cannabis in children with cancer.”

https://pubmed.ncbi.nlm.nih.gov/37635461/

“In conclusion, cannabinoids have been used for the management of multiple symptoms in children with cancer, including CINV, anorexia, tumor-related epilepsy, and cancer-related pain. Cannabis products may have therapeutic applications for symptom management in children with cancer. “

https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.34920

Etoricoxib-Cannabidiol Combo: Potential Role in Glioblastoma Treatment and Development of PLGA-Based Nanoparticles

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“Background: Glioblastoma (GBM) is the most frequently occurring primary malignant central nervous system tumor, with a poor prognosis and median survival below two years. Administration of a combination of non-steroidal anti-inflammatory drugs and natural compounds that exhibit a curative or prophylactic effect in cancer is a new approach to GBM treatment. This study aimed to investigate the synergistic antitumor activity of etoricoxib (ETO) and cannabidiol (CBD) in a GBM cell line model, and to develop poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles (NPs) for these two substances.

Methods: The activity of ETO+CBD was determined using the MTT test, cell-cycle distribution assay, and apoptosis analysis using two GBM cell lines, namely, T98G and U-138 MG. The PLGA-based NPs were developed using the emulsification and solvent evaporation method. Their physicochemical properties, such as shape, size, entrapment efficiency (EE%), in vitro drug release, and quality attributes, were determined using scanning electron microscopy, diffraction light scattering, high-performance liquid chromatography, infrared spectroscopy, and differential scanning calorimetry.

Results: The combination of ETO and CBD reduced the viability of cells in a dose-dependent manner and induced apoptosis in both tested GBM cell lines. The developed method allowed for the preparation of ETO+CBD-NPs with a spherical shape, mean particle size (MPS) below 400 nm, zeta potential (ZP) values from -11 to -17.4 mV, polydispersity index (PDI) values in the range from 0.029 to 0.256, and sufficient EE% of both drugs (78.43% for CBD, 10.94% for ETO).

Conclusions: The combination of ETO and CBD is a promising adjuvant therapeutic in the treatment of GBM, and the prepared ETO+CBD-NPs exhibit a high potential for further pharmaceutical formulation development.”

https://pubmed.ncbi.nlm.nih.gov/37631318/

https://www.mdpi.com/1999-4923/15/8/2104

Cannabinoids and standardized cannabis extracts inhibit migration, invasion, and induce apoptosis in MCF-7 cells through FAK/MAPK/Akt/NF-κB signaling

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“Background: Breast cancer is the highest incidence of all types of cancer in women, and the cancer metastasis process accounts for a majority of cancer deaths. Two major cannabinoids, Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), from Cannabis sativa are expected to have anti-cancer activity. This study aimed to investigate the effects of THC, CBD, and standardized cannabis extracts (F1, F2, and F3) on migration, invasion, and apoptosis of human breast cancer (MCF-7) cells.

Methods: Cell viability, survival, and apoptosis were determined using the MTT, clonogenic, and nuclear staining assays, respectively, while cancer cell migration and invasion were evaluated by the wound healing, trans-well, and filopodia assays. Western blot analysis was used to find out the mechanisms of the cannabinoids against MCF-7 cells.

Results: CBD, THC, and F1 inhibited filopodia formation, migration, and invasion of MCF-7 cells through suppressing the expression of the FAK, Akt, ERK1/2, p38MAPKs, and NF-κB upstream pathways, as well as inhibiting the Rac1/Cdc42 downstream pathways. In addition, CBD significantly inhibited the mTOR pathway. Furthermore, CBD and F1 induced apoptosis in MCF-7 cells via the Bcl-2/caspase-3 pathways.

Conclusion: These results indicate that THC, CBD, and F1 have great abilities for preventing breast cancer cell metastasis in in vitro experiments.”

https://pubmed.ncbi.nlm.nih.gov/37625625/

https://www.sciencedirect.com/science/article/abs/pii/S0887233323001169?via%3Dihub

Oral Tetrahydrocannabinol (THC):Cannabinoid (CBD) Cannabis Extract Adjuvant for Reducing Chemotherapy-Induced Nausea and Vomiting (CINV): A Randomized, Double-Blinded, Placebo-Controlled, Crossover Trial

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“Objective: To evaluate the effects of tetrahydrocannabinol (THC):cannabinoid (CBD) (1:1) oil in reducing chemotherapy-induced nausea and vomiting (CINV) in gynecologic cancer patients who received moderate-to-high emetogenic chemotherapy.

Material and method: This was a randomized, double-blinded, crossover and placebo-controlled trial. The study was conducted at the Gynecologic Oncology Units, Bhumibol Adulyadej Hospital (BAH), Royal Thai Air Force, Bangkok, Thailand, between August and November 2022. Participants had gynecologic cancer and received moderate-to-high emetogenic chemotherapy. Subjects were randomized and divided into two groups (A and B) based on the block of four randomization method. In the first cycle, groups A and B received THC:CBD extract oil 1:1 (TCEO) and placebo before chemotherapy administration. In the second cycle, groups A and B received placebo and TCEO before chemotherapy administration. Both groups received per protocol antiemetic medication during chemotherapy. Nausea score and side effects were recorded.

Results: A total of 60 cases were recruited. After exclusion, 54 cases were included in the study. The mean age of participants was 54.4 years. The mean body mass index (BMI) was 26.5 kg/m2. Fifty-nine (21/54) percent cases were the advanced stages of cancer. The nausea score of TCEO and placebo groups were 2.11 and 2.99, respectively (P < 0.05). More than half of the participants (36/54) reported dizziness and sedation side effects. Dry mouth, confusion, anxiety, and palpitation of both groups were comparable.

Conclusion: The cannabinoid extract (THC:CBD) was an appropriate adjuvant agent to reduce CINV in patients with gynecologic cancer who received high-emetogenic chemotherapy. Dizziness and sedation were the major side effects.”

https://pubmed.ncbi.nlm.nih.gov/37608911/

https://www.dovepress.com/oral-tetrahydrocannabinol-thccannabinoid-cbd-cannabis-extract-adjuvant-peer-reviewed-fulltext-article-IJWH

Single-cell analyses reveal cannabidiol rewires tumor microenvironment via inhibiting alternative activation of macrophage and synergizes with anti-PD-1 in colon cancer

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“Colorectal tumors often create an immunosuppressive microenvironment that prevents them from responding to immunotherapy.

Cannabidiol (CBD) is a non-psychoactive natural active ingredient from the cannabis plant that has various pharmacological effects, including neuroprotective, antiemetic, anti-inflammatory, and antineoplastic activities.

This study aimed to elucidate the specific anticancer mechanism of CBD by single-cell RNA sequencing (scRNA-seq) and single-cell ATAC sequencing (scATAC-seq) technologies.

Here, we report that CBD inhibits colorectal cancer progression by modulating the suppressive tumor microenvironment (TME).

Our single-cell transcriptome and ATAC sequencing results showed that CBD suppressed M2-like macrophages and promoted M1-like macrophages in tumors both in strength and quantity. Furthermore, CBD significantly enhanced the interaction between M1-like macrophages and tumor cells and restored the intrinsic anti-tumor properties of macrophages, thereby preventing tumor progression. Mechanistically, CBD altered the metabolic pattern of macrophages and related anti-tumor signaling pathways.

We found that CBD inhibited the alternative activation of macrophages and shifted the metabolic process from oxidative phosphorylation and fatty acid oxidation to glycolysis by inhibiting the phosphatidylinositol 3-kinase-protein kinase B signaling pathway and related downstream target genes. Furthermore, CBD-mediated macrophage plasticity enhanced the response to anti-programmed cell death protein-1 (PD-1) immunotherapy in xenografted mice.

Taken together, we provide new insights into the anti-tumor effects of CBD.”

https://pubmed.ncbi.nlm.nih.gov/37577382/

“CBD shapes the TME to prevent tumor progression.”

https://www.sciencedirect.com/science/article/pii/S2095177923000746?via%3Dihub