Category Archives: Cancer

Extraction, GC-MS analysis, cytotoxic, anti-inflammatory and anticancer potential of Cannabis sativa female flower; in vitro, in vivo and in silico

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“This work examines the anticancer activity, the anti-inflammatory nature, and the cytotoxicity of the ethanol extract obtained from the female flowers of Cannabis sativa L using molecular methods in vitro, animal testing in vivo, as well as computational methods and simulations in silico.

From the GC-MS analysis, the following bioactive compounds were found: cannabidiol (CBD), tetrahydrocannabinol (THC), and humulene. The antiproliferative activities of the extract were determined on HeLa cells by using MTT, Crystal Violet, and Trypan Blue assays with an IC50 value suggesting 51%-77.6% lethality.

The bioinformatics analysis of molecular docking proved significant ligand-protein interactions of CBD, THC, and humulene with cancer-associated proteins such as PD-1/PD-L1, TNF-α, and MMP-9. In vivo, breast cancer was first established in female Sprague-Dawley rats with 7,12-dimethylbenz(a)anthracene (DMBA) then treated with cannabinoids either singularly or in combination.

Detailed treatment demonstrated that the use of the three cannabinoids simultaneously yielded the best anticancer and anti-inflammatory outcomes together with the best tumor reduction. The concentration of serum biomarkers of inflammation and tumor progression was substantially reduced in treated groups compared to the control group, which proves the synergistic effects of these cannabinoids in breast cancer therapy.

This study emphasizes the importance of medical Cannabis sativa derivatives in cancer treatment.”

https://pubmed.ncbi.nlm.nih.gov/40008130/

“Cancer still has no known treatment, and research is being conducted to create lead compounds and precursors that could be used as anticancer medications for 1 day. The goal of this study was to identify natural compounds with anticancer properties.

The MTT assay showed that cannabinoids retain anti-proliferative, anti-invasion, and apoptotic effects. IC50 upregulates 51%–77.6% of carcinoma cell death. The synergistic effects of cannabidiol, tetrahydrocannabinol, and humulene significantly suppressed PD-1/PD-L1 expression and oxidative stress, suggesting a possible approach for targeting breast cancer resistance. The greatest effect was obtained when all three compounds were combined, suggesting that the immunosuppressive and oxidative stress-modulatory effects of the compounds occurred synergistically.

Herein, we report comprehensive findings that may be helpful in designing new combinatory therapeutic strategies for breast cancer via the PD-1/PD-L1 pathway and oxidative stress markers. Further studies and trials are needed to identify more cannabinoid-based treatments and to combine pharmacological and cannabinoid drugs to gain remarkable effects against various cancer treatments.”

“Cannabis sativa is the oldest cultivated plant and contains a lot of naturally useful components used by humans. It is used as a source of fuel, food, herbal body care products, and medicines to cure different diseases. It is a plant of the Cannabaceae family. “

https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1546062/full

Mechanisms of Cell Death Induced by Cannabidiol Against Tumor Cells: A Review of Preclinical Studies

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“Commonly known as marijuana or hemp, Cannabis sativa L. (Cannabaceae), contains numerous active compounds, particularly cannabinoids, which have been extensively studied for their biological activities. Among these, cannabidiol (CBD) stands out for its therapeutic potential, especially given its non-psychotropic effects.

This review evaluates the antitumor properties of CBD, highlighting its various mechanisms of action, including the induction of apoptosis, autophagy, and necrosis.

By synthesizing findings from in vitro studies on the cell death mechanisms and signaling pathways activated by CBD in various human tumor cell lines, this literature review emphasizes the therapeutic promise of this natural antineoplastic agent. We conducted a comprehensive search of articles in PubMed, Scopus, Springer, Medline, Lilacs, and Scielo databases from 1984 to February 2022.

Of the forty-three articles included, the majority (68.18%) reported that CBD activates apoptosis, while 18.18% observed simultaneous apoptosis and autophagy, 9.09% focused on autophagy alone, and 4.54% indicated necrosis. The antitumor effects of CBD appear to be mediated by transient receptor potential cation channels (TRPVs) in endometrial cancer, glioma, bladder cancer, and myeloma, with TRPV1, TRPV2, and TRPV4 playing key roles in activating apoptosis.

This knowledge paves the way for innovative therapeutic strategies that may enhance cancer treatment outcomes while minimizing the toxicity and side effects associated with conventional therapies.”

https://pubmed.ncbi.nlm.nih.gov/40006844/

“This review underscores the therapeutic potential of CBD as a promising antitumor agent across various cancer types, particularly through its interaction with transient receptor potential cation channels (TRPVs) and endocannabinoid CB receptors.

Our findings suggest that CBD primarily activates the apoptosis pathway while also engaging autophagy and necrosis, offering a multifaceted strategy for inducing cancer cell death. Moreover, the potential for combination therapies that integrate CBD with established chemotherapeutics highlights the importance of further research to investigate these synergies and optimize therapeutic regimens.

Although regulatory challenges persist, robust scientific evidence demonstrating CBD’s safety and efficacy of CBD will be crucial for advancing its clinical application in oncology.”

https://www.mdpi.com/2223-7747/14/4/585

Cannabinoids as Promising Inhibitors of HER2-Tyrosine Kinase: A Novel Strategy for Targeting HER2-Positive Ovarian Cancer

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“Human epidermal growth factor receptor 2 (HER2) is a transmembrane receptor within the ErbB family that plays a pivotal role in the progression of various aggressive cancers. HER2-positive tumors often develop resistance to standard therapies, necessitating the exploration of innovative treatment options.

Cannabinoids, bioactive compounds from Cannabis sativa such as cannabidiol (CBD), cannabigerol (CBG), and cannabinol (CBN), have gained attention for their potential anticancer properties.

This study evaluates the efficacy of CBD, CBG, and CBN in targeting HER2-positive ovarian cancer through kinase inhibition assays, surface plasmon resonance (SPR), molecular docking, and cell viability assessments.

SPR analysis revealed that cannabinoids bind strongly to HER2-tyrosine kinase (HER2-TK), with CBD showing the highest affinity (K D = 6.16 μM), significantly better than afatinib (K D = 26.30 μM), and CBG demonstrating moderate affinity (K D = 17.07 μM). In kinase inhibition assays, CBG was the most potent inhibitor (IC50 = 24.7 nM), followed by CBD (IC50 = 38 nM), suggesting their ability to disrupt HER2-mediated signaling pathways. Molecular docking studies highlighted critical interactions between cannabinoids and essential HER2 residues (Leu796, Thr862, Asp863). In cell viability assays, CBD and CBG effectively inhibited the growth of HER2-positive SKOV3 cells (IC50 = 13.8 μM and 16.6 μM, respectively), comparable to traditional tyrosine kinase inhibitors.

These findings underscore the therapeutic potential of cannabinoids, particularly CBD and CBG, as alternative or adjunct therapies for HER2-positive cancers, with the promise of mitigating resistance and adverse effects associated with existing treatments.”

https://pubmed.ncbi.nlm.nih.gov/39989803/

“This study provides compelling evidence for the potential of cannabinoids, particularly CBD and CBG, as effective inhibitors of HER2-TK in HER2-positive ovarian cancer. The significant binding affinities and potent inhibitory effects observed in kinase assays and cell viability experiments highlight cannabinoids as promising candidates for alternative or adjunctive therapies, especially in patients facing challenges with conventional treatments.

The findings not only indicate that cannabinoids can disrupt HER2-mediated signaling pathways but also suggest that they may enhance the therapeutic efficacy of existing TKIs while potentially mitigating associated side effects. The molecular docking analysis reinforces the understanding of how cannabinoids interact with critical residues in HER2-TK, revealing a detailed mechanism of action that warrants further exploration. Given the rising concerns regarding resistance to standard HER2-targeted therapies and their adverse effects, the incorporation of cannabinoids into treatment regimens may offer a novel and beneficial strategy for managing HER2-positive ovarian cancer.”

https://pubs.acs.org/doi/10.1021/acsomega.4c11108

Cannabidiol Targets Colorectal Cancer Cells via Cannabinoid Receptor 2, Independent of Common Mutations

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“Cannabidiol (CBD) is a non-neurotoxic, phytocannabinoid from cannabis with reported medicinal properties, including antiepileptic and anti-inflammatory activity.

Several in vitro and in vivo studies have shown that CBD has antitumor potential against colorectal cancer (CRC), the third deadliest cancer in the world. However, as different mutations influence the antitumor effects and CBD can bind a variety of receptors, it is yet to be determined whether specific CRC mutations affect CBD’s efficacy in treatment of CRC.

To investigate this, we selected four CRC cell lines, including HCT116, HT-29, LS174T, and LS153, which harbor distinct mutations. Cells were treated with a range of concentrations of CBD to evaluate its cytotoxic effects and impact on cell proliferation, migration, and invasion by using a live-cell imaging system. IC50 values were then calculated for each parameter. The level of endoplasmic reticulum (ER) stress pathway markers was also measured using qRTPCR. The requirements for CB1 or CB2 receptor-medicated signaling were investigated using the selective inhibitors AM251 and SR144528, respectively.

Our results demonstrate that CBD induces apoptosis and halts proliferation, migration, and invasion of CRC cell lines in a concentration-dependent manner.

CBD showed potent antitumor effects in the tested cell lines with no obvious effect from different mutations such as KRAS, BRAF, APC, PTEN, etc. CBD also induced ER stress in CRC cells but not in healthy intestinal organoids. Cotreatment with SR144528 inhibited the effects of indicating involvement of CB2 receptor activation in the anticancer effects of CBD.

Together, these results demonstrated that CBD could be effective for CRC regardless of the underlying mutation through CB2 receptor activation.”

https://pubmed.ncbi.nlm.nih.gov/39974647/

https://pubs.acs.org/doi/10.1021/acsptsci.4c00644

UK Medical Cannabis Registry: An Analysis of Clinical Outcomes of Medicinal Cannabis Therapy for Cancer Pain

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“Cancer pain (CP) is a prevalent condition with limited pharmacotherapeutic options. Cannabis-based medicinal products (CBMPs) have shown analgesic effects, but their efficacy in CP remains contentious.

This study aims to evaluate the change in patient-reported outcome measures (PROMs) and adverse events (AEs) in CP patients treated with CBMPs.

A case series was conducted using prospectively collected clinical data from the UK Medical Cannabis Registry. Primary outcomes were the changes in the Brief Pain Inventory (BPI), pain visual analogue scale (Pain-VAS), EQ-5D-5L, Generalized Anxiety Disorder-7 (GAD-7), Patient Global Impression of Change (PGIC) and Single-Item Sleep Quality Scale (SQS) questionnaires from baseline to 1, 3, and 6 months. AEs were recorded and graded. p < 0.050 was considered statistically significant. One hundred and sixty-eight participants were included.

CBMPs were associated with improvements in all pain-specific PROMs at all follow-up periods (p < 0.050).

Improvements in GAD-7, SQS, and EQ-5D-5L index scores were also observed (p < 0.050). Twenty-nine AEs (17.26%) were reported by five patients (2.98%), mostly mild-to-moderate (72.41%). Although the observational design means causality cannot be established, the findings support the development of future randomized controlled trials into CP management with CBMPs.”

https://pubmed.ncbi.nlm.nih.gov/39921589/

“This study found that initiation of CBMPs is associated with improvements in pain-specific and general health-related quality of life outcomes in CP patients over six months, with a relatively low incidence of mild-to-moderate AEs and no life-threatening AEs.”

https://www.tandfonline.com/doi/full/10.1080/15360288.2025.2457101

The impact of cannabis on immune checkpoint inhibitor therapy: a systematic review of immunomodulatory effects of cannabis in patients with and without cancer

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“Purpose: Cannabis is commonly used among patients with cancer for palliative benefit. As the use of immune checkpoint inhibitors (ICIs) for cancer therapy increases, there is concern about potential interactions between ICIs and cannabis. Preclinical studies suggest that cannabis leads to immunosuppression, which could impair the function of ICIs. However, only a few clinical studies have investigated this relationship. The goal of this review is to synthesize reported immunomodulatory effects of cannabis in patients with and without cancer in order to better understand whether these preclinical findings translate to the clinical space.

Methods: A database search was conducted through Ovid Medline to identify relevant articles. Clinical studies investigating cannabis use in humans and the immune system were included. Preclinical studies and case studies were excluded. Information pertaining to immune changes with cannabis exposure was abstracted.

Results: Forty studies met inclusion criteria, including 9 randomized, placebo-controlled clinical trials. Analysis of immune-related markers demonstrated no change in cytokines, T-cell counts, and CRP in most studies with cannabis exposure.

Among patients with autoimmune diseases, cannabis use showed improvements in clinical symptoms even while objective laboratory immune markers remained unchanged.

Conclusion: We did not find evidence of meaningful changes in immune parameters with cannabis use in the clinical setting across multiple diseases. In particular, immune markers relevant to ICI function did not appear to be associated with cannabis use. This evidence may provide some reassurance to patients and oncologists contemplating concomitant cannabis use with ICIs; however, additional well-controlled prospective studies are warranted in this setting.”

https://pubmed.ncbi.nlm.nih.gov/39921765/

https://link.springer.com/article/10.1007/s00520-025-09218-x

Cannabidiol attenuates lipid metabolism and induces CB1 receptor-mediated ER stress associated apoptosis in ovarian cancer cells

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“Ovarian cancer (OC) is the most deadly gynecological tumor. OC cells utilize cellular metabolic reprogramming to gain a survival advantage, particularly through aberrant lipid metabolic process.

As the primary ingredient in exogenous cannabinoids, cannabidiol (CBD) has been confirmed to exhibit antitumor activity in preclinical studies. However, it is still unclear whether CBD can disrupt fatty acid metabolism and induce apoptosis in OC cells.

In this study, we have demonstrated that CBD significantly inhibits the proliferation of OCs through a cannabinoid receptor type 1 (CB1R)-mediated manner.

Fatty acid metabolic profiling and flow cytometry analysis revealed that CBD has the ability to decrease fatty acid levels and significantly suppress the transcription of genes involved in fatty acid uptake and synthesis in ES-2 cells. In addition, the analysis from RNA-seq and real-time RT-PCR revealed that CBD activated the endoplasmic reticulum (ER) stress pathway. Conversely, by supplementation with unsaturated fatty acid or blocking CB1R, ER stress or reactive oxygen species (ROS) signals with specific inhibitors could significantly relieve CBD induced, dose-dependent, ER stress associated apoptosis, G0-G1 phase arrest, and mitochondrial dysfunction.

Taken collectively, these data indicate that CBD may disrupt lipid metabolism, and lead to ER stress-related apoptosis in OCs. Our findings may provide a theoretical mechanism for anti-ovarian cancer using CBD.”

https://pubmed.ncbi.nlm.nih.gov/39910152/

“Preclinical studies have demonstrated that CBD, either as a monotherapy or in conjunction with other treatments, holds potential as a novel anti-tumor, anti-inflammatory, and analgesic agent. Our results demonstrated that CBD promoted OC cells apoptosis and G0-G1 phase arrest by disrupting the CBR1-mediated lipid metabolism and ER stress- and mitochondrial dysfunction-associated apoptosis signaling pathways (Fig. 8). Therefore, CBD may serve as a potential candidate for adjuvant therapy in the treatment of ovarian cancer. However, larger-scale clinical studies involving more patient samples and detailed dose-response relationship analyses are still needed to confirm the efficacy of CBD in cancer patients.”

https://www.nature.com/articles/s41598-025-88917-1

GPR55 in the tumor microenvironment of pancreatic cancer controls tumorigenesis

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“Background: The G protein-coupled receptor 55 (GPR55) is part of an expanded endocannabinoid system (ECS), and plays a pro-tumorigenic role in different cancer models, including pancreatic cancer. Next to cancer cells, various cells of the immune tumor microenvironment (TME) express receptors of the ECS that critically determine tumor growth. The role of GPR55 in cancer cells has been widely described, but its role in the immune TME is not well understood.

Methods: We intended to uncover the role of GPR55 in tumor immunity in a model of pancreatic ductal adenocarcinoma (PDAC). To this end, a KPCY tumor cell line or a GPR55-overexpressing KPCY cell line (KPCY55) from murine PDAC were subcutaneously injected into wildtype (WT) and GPR55 knockout (KO) mice, and immune cell populations were evaluated by flow cytometry.

Results: Deficiency of GPR55 in the TME led to reduced tumor weight and volume, and altered the immune cell composition of tumors, favoring an anti-tumorigenic environment by increasing the number of CD3+ T cells, particularly CD8+ T cells, and the expression of PDL1 on macrophages. RNA-seq pathway analysis revealed higher T cell activity in KPCY55 tumors of GPR55 KO vs. WT mice. In addition, tumors from GPR55 KO mice displayed increased levels of T cell chemokines Cxcl9 and Cxcl10. Migration of T cells from GPR55 KO mice towards CXCL9 was increased in comparison to T cells from WT mice, suggesting that a CXCR3/CXCL9 axis was involved in T cell influx into tumors of GPR55 KO mice. Notably, anti-PD-1 immunotherapy increased tumor burden in WT mice, while this effect was absent in the GPR55 KO mice.

Conclusion: Our study indicates that GPR55 in TME cells may drive tumor growth by suppressing T cell functions, such as migration, in a model of PDAC, making it an interesting target for immunotherapies.”

https://pubmed.ncbi.nlm.nih.gov/39885986/

“Our study indicates that GPR55 in TME cells may drive tumor growth by suppressing T cell functions, such as migration, in a model of PDAC, making it an interesting target for immunotherapies.”

https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1513547/full

“GPR55 – a putative “type 3″ cannabinoid receptor in inflammation”

https://pubmed.ncbi.nlm.nih.gov/26669245/

“Therapeutic targeting of the tumor microenvironments with cannabinoids and their analogs: Update on clinical trials”

https://pubmed.ncbi.nlm.nih.gov/37146933/

“Anti-proliferative and apoptotic effect of cannabinoids on human pancreatic ductal adenocarcinoma xenograft in BALB/c nude mice model”

https://pubmed.ncbi.nlm.nih.gov/38499634/

“Antitumor Effects of Cannabinoids in Human Pancreatic Ductal Adenocarcinoma Cell Line (Capan-2)-Derived Xenograft Mouse Model”

https://pubmed.ncbi.nlm.nih.gov/35937289/

“Cannabinoid improves survival rates of mice with pancreatic cancer”

https://medicalxpress.com/news/2018-07-cannabinoid-survival-mice-pancreatic-cancer.html

Cannabidiol Ameliorates Doxorubicin-Induced Myocardial Injury via Activating Hippo Pathway

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“Background: Doxorubicin (DOX) is a chemotherapeutic agent widely used for cancer treatment and has non-negligible cardiotoxicity. Some previous studies have reported that cannabidiol (CBD) has cardioprotective effects. In this study, we evaluated the protective effects of CBD against DOX-induced cardiomyocyte injury, and explored the downstream molecular mechanism.

Methods and materials: GSE193861, containing healthy myocardial tissues and myocardial tissues with DOX-induced injury, was analyzed to screen for the involved proteins and pathways. Molecular docking was performed to identify candidate drugs. After H9c2 cells were treated with DOX and CBD, their viability, oxidative stress, and apoptosis were assessed. After YAP depletion, the role of the Hippo pathway in CBD function was investigated. C57BL/6 mice were treated with DOX to establish an in vivo model, and CBD and verteporfin (VP) were used to treat the mice. Histological analyses and immunofluorescence were used to evaluate myocardial tissue injury, and apoptosis and oxidative stress of the myocardial tissues were also analyzed. Western blotting was used to investigate the regulatory effects of CBD on the Hippo and apoptosis-related pathways.

Results: Bioinformatic analysis suggested that the Hippo pathway was a crucial pathway involved in DOX-induced myocardial injury. Molecular docking showed that CBD targeted multiple regulators of the Hippo pathway. CBD showed cardioprotective effects against DOX-induced myocardial injury both in vitro and in vivo and regulated Hippo pathway activity in cardiomyocytes. After inactivation of the Hippo pathway by YAP knockdown or VP intervention, the protective effects of CBD were reversed.

Conclusion: For the first time, we revealed that CBD is likely to reduce DOX-induced myocardial injury by regulating the Hippo signaling pathway.”

https://pubmed.ncbi.nlm.nih.gov/39876987/

“Overall, this study reports that CBD alleviates DOX-induced myocardial injury by regulating the Hippo pathway.”

https://www.dovepress.com/cannabidiol-ameliorates-doxorubicin-induced-myocardial-injury-via-acti-peer-reviewed-fulltext-article-DDDT

Exploring the Therapeutic Potential of Cannabidiol in U87MG Cells: Effects on Autophagy and NRF2 Pathway

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“Cannabinoids include both endogenous endocannabinoids and exogenous phytocannabinoids, such as cannabidiol (CBD), and have potential as therapeutic agents in cancer treatment due to their selective anticancer activities.

CBD exhibits both antioxidant and pro-oxidant effects depending on its concentration and cell types. These properties allow CBD to influence oxidative stress responses and potentially enhance the efficacy of antitumor therapies.

In this study, we treated U87MG glioma cells with low dose (1 μM) CBD and evaluated its molecular effects.

Our findings indicate that CBD reduced cell viability by 20% (p < 0.05) through the alteration of mitochondrial membrane potential. The alteration of redox status by CBD caused an attempt to rescue mitochondrial functionality through nuclear localization of the GABP transcription factor involved in mitochondria biogenesis. Moreover, CBD treatment caused an increase in autophagic flux, as supported by the increase in Beclin-1 and the ratio of LC3-II/LC3-I. Due to mitochondria functionality alteration, pro-apoptotic proteins were induced without activating apoptotic effectors Caspase-3 or Caspase-7. The study of the transcription factor NRF2 and the ubiquitin-binding protein p62 expression revealed an increase in their levels in CBD-treated cells.

In conclusion, low-dose CBD makes U87MG cells more vulnerable to cytotoxic effects, reducing cell viability and mitochondrial dynamics while increasing autophagic flux and redox systems. This explains the mechanisms by which glioma cells respond to CBD treatment.

These findings highlight the therapeutic potential of CBD, suggesting that modulating NRF2 and autophagy pathways could represent a promising strategy for glioblastoma treatment.”

https://pubmed.ncbi.nlm.nih.gov/39857352/

“Our study demonstrates that low-dose CBD treatment (1 μM) in U87MG glioblastoma cells stimulates the autophagy process, which is essential for mitochondrial renewal, contributing to an increase in mitochondria with altered membrane potential. Moreover, CBD-treated U87MG cells present an abnormal activation of the NRF2 pathway, reducing the expression of antioxidant target genes and consequently altering mitochondrial integrity. These molecular effects suggest that CBD could have therapeutic repercussions or be useful in the development of multi-target agents acting on the NRF2 mitochondrial biogenesis–autophagy axis.”

https://www.mdpi.com/2076-3921/14/1/18