Category Archives: Cancer

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

Eight Weeks of Daily Cannabidiol Supplementation Improves Sleep Quality and Immune Cell Cytotoxicity

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“Background: The endocannabinoid system is active in nervous and immune cells and involves the expression of two cannabinoid receptor genes (CB1 and CB2), along with endogenous endocannabinoid ligands, 2-arachidonoyl glycerol (2-AG) and arachidonoyl ethanolamide (anandamide), and their synthetic enzymes. Cannabidiol (CBD) is a non-intoxicating exogenous cannabinoid agonist derived from plants that, at high doses, has received FDA approval as an anticonvulsant for epileptic seizures, and at low doses is marketed as a food-grade supplement for improved mental health, sleep quality, and immunological function. At present, the predominance of published CBD clinical research has focused on ameliorative or disease-specific intervention, with few trials investigating CBD effects in healthy populations.

Methods: This clinical study aimed to investigate the effects of 8 weeks of 50 mg oral CBD on mental health, sleep quantity and quality, and immune cell function in healthy, college-aged individuals. Twenty-eight participants (average age 25.9 ± 6.1 y) were randomized to receive either daily oral capsules of 50 mg of CBD (CB, n = 14) or a calorie-matched placebo (CN, n = 14). Participants completed pre- and post-intervention assessments, including anthropometric measurements, mental health surveys, sleep analysis, and immunological function assessments.

Results: After completing the 8-week intervention, there were no significant changes in body weight and BMI (CN: 1.09 ± 0.89%: CB: 1.41 ± 1.07%), or body fat percentage (CN: 9.01 ± 7.51%: CB: 8.57 ± 7.81%), respectively (values are % change pre to post, p > 0.05). There were also no significant differences between CB and CN groups with respect to mental health measures, sleep quantity, or circulating immunophenotype as a result of the intervention. However, the CB group experienced significant improvements in sleep quality measured objectively using a sleep questionnaire (p = 0.0023) and enhanced Natural Killer (NK) immune cell function assessed in situ (p = 0.0125).

Conclusions: Eight weeks of daily 50 mg CBD may improve sleep quality, and NK immunosurveillance in healthy, younger adults.”

https://pubmed.ncbi.nlm.nih.gov/37836465/

“These results collectively support the notion that low dose CBD supplementation may offer benefits in enhancing sleep quality in humans and improving immunosurveillance against cancer cells in situ.”

https://www.mdpi.com/2072-6643/15/19/4173

The potential protective and therapeutic effects of cannabidiol oil on experimental Leukemia induced by DMBA in male rats

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“Background: 7,12-Dimethylbenzanthracene (DMBA) is a member of the polycyclic aromatic hydrocarbon family. It is a member of the polycyclic aromatic hydrocarbon family. It is a mutagenic, carcinogenic, and immunosuppressor agent. Cannabidiol (CBD) is a phytocannabinoid. It has anticonvulsant, anti-inflammatory, anti-anxiety, antioxidant, and anti-cancer properties. The purpose of this study was to investigate the possible protective and therapeutic benefits of CBD oil in DMBA-induced leukemia in rats.

Method: Experimental animals were divided into six groups of five rats each. Group 1 (normal control) included healthy rats. Group 2 included normal rats that received olive oil. Group 3 included normal rats that received CBD. Group 4 included the DMBA-induced leukemic group. Group 5 (prophylactic group) included rats that received CBD as a prophylaxis before IV injection with DMBA. Group 6 (treated group) included DMBA-induced leukemic rats that received CBD as treatment. Liver functions (total, direct and indirect bilirubin, alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate aminotransferase (AST), albumin, globulin, and albumin globulin ratio) were measured. Superoxide dismutase (SOD) and catalase (CAT) were also measured. Total RNA extraction followed by-real time qRT-PCR gene expression of LC3-II, Beclin, mTOR, and P62 was performed. Histopathological examination of liver and spleen tissues was performed.

Results: Administration of CBD in groups 5 and 6 resulted in a significant improvement of the levels of liver functions compared to the leukemic untreated rats. Also, the levels of catalase and SOD significantly increased after treatment with CBD compared to the leukemic group. After treatment with CBD in groups 5 and 6, there were downregulations in the expression of all studied genes compared to leukemic untreated rats. Treatment with CBD was more statistically effective than prophylactic use.

Conclusion: Administration of CBD resulted in a significant improvement in the biochemical, antioxidant status, morphological, and molecular measures in DMBA-induced leukemia in adult male rats. The therapeutic use was more effective than the prophylactic one.”

https://pubmed.ncbi.nlm.nih.gov/37837474/

https://link.springer.com/article/10.1007/s00210-023-02737-6

Cell death induction and intracellular vesicle formation in human colorectal cancer cells treated with Δ9-Tetrahydrocannabinol

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“Background: Δ9-Tetrahydrocannabinol (Δ9-THC) is a principal psychoactive extract of Cannabis sativa and has been traditionally used as palliative medicine for neuropathic pain. Cannabidiol (CBD), an extract of hemp species, has recently attracted increased attention as a cancer treatment, but Δ9-THC is also requiring explored pharmacological application.

Objective: This study evaluated the pharmacological effects of Δ9-THC in two human colorectal cancer cell lines. We investigated whether Δ9-THC treatment induces cell death in human colorectal cancer cells.

Methods: We performed an MTT assay to determine the pharmacological concentration of Δ9-THC. Annxein V and Western blot analysis confirmed that Δ9-THC induced apoptosis in colorectal cancer cells. Metabolic activity was evaluated using MitoTracker staining and ATP determination. We investigated vesicle formation by Δ9-THC treatment using GW9662, known as a PPARγ inhibitor.

Results: The MTT assay showed that treatment with 40 μM Δ9-THC and above inhibited the proliferation of colorectal cancer cells. Multiple intracytoplasmic vesicles were detected upon microscopic observation, and fluorescence-activated cell sorting analysis showed cell death via G1 arrest. Δ9-THC treatment increased the expression of cell death marker proteins, including p53, cleaved PARP-1, RIP1, and RIP3, suggesting that Δ9-THC induced the death of colorectal cancer cells. Δ9-THC treatment also reduced ATP production via changes in Bax and Bcl-2. Δ9-THC regulated intracytoplasmic vesicle formation by modulating the expression of PPARγ and clathrin, adding that antiproliferative activity of Δ9-THC was also affected.

Conclusion: In conclusion, Δ9-THC regulated two functional mechanisms, intracellular vesicle formation and cell death. These findings can help to determine how cannabinoids can be used most effectively to improve the efficacy of cancer treatment.”

https://pubmed.ncbi.nlm.nih.gov/37837516/

https://link.springer.com/article/10.1007/s13258-023-01466-7

Reversion of chemoresistance by endocannabinoid-induced ER stress and autophagy activation in ovarian cancer

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“The difficulty of detection at an early stage and the ease of developing resistance to chemotherapy render ovarian cancer (OVC) difficult to cure. Although several novel cancer therapies have been developed recently, drug resistance remains a concern since chemotherapy remains as the most commonly used treatment for cancer patients. Therefore, there is an urgent need to reclaim potential combination treatments for OVC.

So far, there have been several research targeting the endocannabinoid system (ECS) in cancer. Among the various cannabinoid-based drugs, endocannabinoids, which are lipid molecules generated in the body, have been reported to produce many anti-tumor effects; however, research investigating the anti-chemoresistance effect of endocannabinoids in OVC remains unclear.

In this study, we aimed to combine endocannabinoids, anandamide (AEA), and 2-arachidonoylglycerol (2-AG) with chemotherapeutic drugs as a combination approach to treat OVC.

Our results showed that OVC cells expressed both cannabinoid receptors (CBR), CB1 and CB2, suggesting the possibility of endocannabinoid system (ECS) as a target. We found that the anti-chemoresistance effect mediated by endocannabinoids was caused by upregulation of ceramide levels, leading to severe endoplasmic reticulum (ER) stress and increased autophagy in chemoresistant cancer cells. Therefore, chemoresistant cancer cell growth was inhibited, and cell apoptosis was induced under combined treatments. Based on our results, endocannabinoids overcomed chemoresistance of OVC cells in vitro.

Our findings suggest that drugs targeting ECS may have the potential to be adjuvants for chemotherapy by increasing the efficacy of chemotherapeutic drugs and decreasing their side effects.”

https://pubmed.ncbi.nlm.nih.gov/37818056/

Cannabinol inhibits cell growth and triggers cell cycle arrest and apoptosis in cancer cells

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Biocatalysis and Agricultural Biotechnology

“Cancer is one of the most difficult diseases to treat and cure.”

“Cannabinol (CBN), one of the active ingredients from the cannabis plant, is the breakdown molecule of Δ9-tetrahydrocannabinol (Δ9-THC) which is the most abundant psychoactive cannabinoid.”

“Cannabinol (CBN) is a weak-psychoactive cannabinoid and has been shown to exert several bio-logical activities. At the same time, not much is known about the anti-cancer activities of CBN. In this report, we characterized the anti-tumor effects of CBN on the glioma A172, liver cancer HepG2 and breast cancer HCC1806 cell lines.

We found that CBN reduces the proliferation of the analyzed cancer cells and modulates the level of cannabinoid receptors, including GPR18, CB2 and GPR55. Furthermore, CBN inhibits the ERK1/2 pathway in A172 and HepG2 cells, while suppressing the AKT pathway in HCC1086 cells. Moreover, CBN may cause apoptosis through downregulation of p21 and p27 as well as a cell cycle arrest at G1 or S-phase via decreasing the CDK1, CDK2, and cyclin E1 levels.

Taken together, these results offer new insights into the anti-cancer properties of CBN.”

“CBN, one of the weak-psychoactive cannabinoids, have demonstrated various medicinal properties, including anti-inflammatory, antibacterial, analgesic and even anti-tumor.”

“In this study, we revealed the antitumor activity of CBN in three different tumor cell lines, glioma A172, liver cancer HepG2 and breast cancer HCC1806 cell lines. We report that cannabinol inhibits proliferation of several cancer cell lines by regulation of the signaling pathways involving ERK and AKT as well as by altering the expression of cannabinoid receptors. Moreover, we also found that CBN induces apoptosis and cell cycle arrest and partially uncovered underlying molecular mechanisms. Our findings provide novel information about the anti-cancer properties of CBN and justify further research to investigate the role of CBN as cancer therapeutic.”

https://www.sciencedirect.com/science/article/abs/pii/S1878818123000282

Cannabidiol Antiproliferative Effect in Triple-Negative Breast Cancer MDA-MB-231 Cells Is Modulated by Its Physical State and by IGF-1

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“Cannabidiol (CBD) is a non-psychoactive phytocannabinoid that has been discussed for its safety and efficacy in cancer treatments. For this reason, we have inquired into its use on triple-negative human breast cancer. Analyzing the biological effects of CBD on MDA-MB-231, we have demonstrated that both CBD dosage and serum concentrations in the culture medium influence its outcomes; furthermore, light scattering studies demonstrated that serum impacts the CBD aggregation state by acting as a surfactant agent. Pharmacological studies on CBD in combination with chemotherapeutic agents reveal that CBD possesses a protective action against the cytotoxic effect exerted by cisplatin on MDA-MB-231 grown in standard conditions. Furthermore, in a low serum condition (0.5%), starting from a threshold concentration (5 µM), CBD forms aggregates, exerts cytostatic antiproliferative outcomes, and promotes cell cycle arrest activating autophagy. At doses above the threshold, CBD exerts a highly cytotoxic effect inducing bubbling cell death. Finally, IGF-1 and EGF antagonize the antiproliferative effect of CBD protecting cells from harmful consequences of CBD aggregates. In conclusion, CBD effect is strongly associated with the physical state and concentration that reaches the treated cells, parameters not taken into account in most of the research papers.”

https://pubmed.ncbi.nlm.nih.gov/35806150/

“Among the various biological properties of phytocannabinoids, their ability to induce antiproliferative effects in different human cancer cells raises the scientific interest in their therapeutic potential in the field of oncology.”

https://www.mdpi.com/1422-0067/23/13/7145

Anti-proliferative effect of Cannabidiol in Prostate cancer cell PC3 is mediated by apoptotic cell death, NFκB activation, increased oxidative stress, and lower reduced glutathione status

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“Prostate cancer is the second most frequent cancer diagnosed in men in the world today. Almost all prostate cancers are adenocarcinomas and develop from gland cells. We used the PC3 prostate cancer cell line, which is well studied and derived from a bone metastasis of a grade IV prostatic adenocarcinoma.

Cannabidiol (CBD), a major non-psychoactive constituent of cannabis, is a cannabinoid with anti-tumor properties but its effects on prostate cancer cells are not studied in detail.

Here, we found cannabidiol decreased prostate cancer cell (PC3) viability up to 37.25% and induced apoptotic cell death in a time and dose-dependent manner. We found that CBD activated the caspases 3/7 pathways and increased DNA fragmentation. Furthermore, we observed an increase of pro-apoptotic genes Bax, an increased level of reactive oxygen species, lower reduced glutathione level, and altered mitochondrial potential in response to CBD treatment leading to lower cellular ATP.

Overall, our results suggest that CBD may be effective against prostate cancer cells.”

https://pubmed.ncbi.nlm.nih.gov/37796968/

“In summary, we have demonstrated CBD as a potential therapeutic molecule in the treatment of prostate cancer based on its properties of anti-proliferative effect on PC3 cancer cells by promoting intrinsic apoptotic pathway via mitochondrial and NFkB activation followed by intracellular ROS generation and reducing cellular redox status of glutathione.”

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0286758

Cannabinoids in Breast Cancer: Differential Susceptibility According to Subtype

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“Although cannabinoids have been used for centuries for diverse pathological conditions, recently, their clinical interest and application have emerged due to their diverse pharmacological properties. Indeed, it is well established that cannabinoids exert important actions on multiple sclerosis, epilepsy and pain relief.

Regarding cancer, cannabinoids were first introduced to manage chemotherapy-related side effects, though several studies demonstrated that they could modulate the proliferation and death of different cancer cells, as well as angiogenesis, making them attractive agents for cancer treatment.

In relation to breast cancer, it has been suggested that estrogen receptor-negative (ER–) cells are more sensitive to cannabinoids than estrogen receptor-positive (ER+) cells. In fact, most of the studies regarding their effects on breast tumors have been conducted on triple-negative breast cancer (TNBC). Nonetheless, the number of studies on human epidermal growth factor receptor 2-positive (HER2+) and ER+ breast tumors has been rising in recent years. However, besides the optimistic results obtained thus far, there is still a long way to go to fully understand the role of these molecules. This review intends to help clarify the clinical potential of cannabinoids for each breast cancer subtype.”

https://pubmed.ncbi.nlm.nih.gov/35011388/

“Cannabinoids have been used for centuries in several therapeutic applications. Regarding cancer, the use of cannabinoids has already been approved in several countries for the relief of chemotherapy-associated effects, but their clinical potential is greater than initially thought, and their clinical interest has been rising in recent years. Pre-clinical studies have demonstrated that cannabinoids exert important antitumor properties in the main breast cancer subtypes, particularly in TNBC, where different phytocannabinoids and synthetic cannabinoids have shown interesting therapeutic actions.”

“Thus, it is strongly believed that Cannabis, being an important natural source of many cannabinoids, may be a potential therapeutic option for the treatment or modulation of different physiological processes and, even, pathological conditions, such as cancer.”

https://www.mdpi.com/1420-3049/27/1/156

“Experimental evidence accumulated during the last decade supports that cannabinoids, the active components of Cannabis sativa and their derivatives, possess anticancer activity. Thus, these compounds exert anti-proliferative, pro-apoptotic, anti-migratory and anti-invasive actions in a wide spectrum of cancer cells in culture. Moreover, tumor growth, angiogenesis and metastasis are hampered by cannabinoids in xenograft-based and genetically-engineered mouse models of cancer. This review summarizes our current knowledge on the anti-tumor potential of cannabinoids in breast cancer, which suggests that cannabinoid-based medicines may be useful for the treatment of most breast tumor subtypes.”

https://www.sciencedirect.com/science/article/pii/S0305737212001399