A new study adds mechanistic detail to earlier evidence that cannabidiolic acid (CBDA) can interfere with the migration of highly aggressive MDA-MB-231 breast cancer cells. Researchers found that CBDA inhibited Rho-associated kinases (ROCKs), impaired tail retraction, altered cell shape and caused vinculin to accumulate at the trailing edge—revealing another way this cannabis-derived compound may disrupt cellular behavior involved in cancer spread.
“We previously reported that cannabidiolic acid (CBDA), a major cannabinoid constituent of the fiber-type cannabis plant, abrogates the migration of highly aggressive human breast cancer MDA-MB-231 cells and activates the small GTPase RhoA by inhibiting protein kinase A. However, the mechanism(s) mediating RhoA signaling, which decreases cell migration, have not yet been comprehensively elucidated.
RhoA is an upstream mediator of Rho-associated kinases (ROCKs), diaphanous-related formins (DIAPHs), the RhoA-ROCK pathway (tail retraction) and the RhoA-DIAPH pathway (lamellipodia formation).
Herein, we identified CBDA as an inhibitor of ROCKs (at approximately 25 μM), which markedly elongated the cell body of MDA-MB-231 cells, similar to Y-27632, an established ROCK inhibitor.
CBDA stimulated lamellipodia formation at the leading edge, whereas NSC23766 (an established Rac1 inhibitor) completely blocked this elongated morphology. Biochemical analyses, including time-lapse imaging and confocal laser scanning microscopy, revealed that, compared to Y-27632, CBDA can induce impaired tail retraction coupled with unidirectional elongation of the cell body, upregulate the mRNA expression of DIAPHs and accumulate vinculin, an adhesion protein, at the trailing edge without affecting its expression.
These results indicate the potential of CBDA as a new candidate for the synthesis of ROCK inhibitors, which can evoke the directed elongation of MDA-MB-231 cells.”
Researchers examining cannabidiol (CBD) in HER2-positive breast cancer cells found that CBD significantly reduced HER2 gene expression while activating endoplasmic reticulum (ER) stress pathways, decreasing cell viability, and increasing apoptosis. The findings identify another potential molecular mechanism behind CBD’s previously observed anticancer activity in breast cancer and suggest that CBD warrants further investigation both alone and in combination with HER2-targeted therapy.
“Cannabidiol (CBD) has attracted attention as a potential anticancer agent due to its observed efficacy, particularly in breast cancer. However, the exact molecular pathway through which it exerts its anticancer effects remains unknown. The present study aimed to investigate the effects of CBD on the HER2 receptor, endoplasmic reticulum (ER) stress signaling pathway, and apoptosis in HER2-positive breast cancer cells, as well as to examine the effect of trastuzumab (TZB), used in treatment, on the ER stress signaling pathway.
Methods
For this purpose, SKBR3 cells were treated with CBD at three different concentrations (9.38, 18.75, and 37.5 µM), TZB at 62.5 µg/mL, and two combinations of TZB and CBD (18.75 µM CBD + 62.5 µg/mL TZB and 37.5 µM CBD + 62.5 µg/mL TZB). Cell proliferation was assessed using real-time cell analysis, while expression levels of ER stress-associated genes were measured by qPCR. Apoptosis was analyzed by Annexin V/PI flow cytometry.
Results
Findings revealed that CBD, TZB, or their combination were associated with reduced cell proliferation, significant activation of ER stress pathways, and increased apoptosis, while CBD was associated with marked downregulation of HER2 gene expression. Treatment with 9.38 µM CBD, 18.75 µM CBD, 37.5 µM CBD, 62.5 µg/mL TZB, 18.75 µM CBD + 62.5 µg/mL TZB, and 37.5 µM CBD + 62.5 µg/mL TZB significantly increased GRP78, PERK, IRE1, ATF6, eIF2A, ATF4, CHOP, and XBP1s gene expression levels, and significantly decreased HER2 gene expression at all doses except 62.5 µg/mL TZB. All doses significantly increased the total number of apoptotic cells and were associated with significantly reduced cell viability.
Conclusions
The present findings demonstrated that both TZB and CBD are associated with activation of the ER stress response and induction of apoptosis in HER2-positive breast cancer cells, and that CBD is associated with downregulation of HER2 receptor gene expression. Collectively, our results indicate that CBD may have potential as an adjunct or alternative strategy in HER2-positive breast cancer, although further in vivo studies are required to evaluate the efficacy and safety of its combination with low-dose TZB.”
This study examined how people with cancer described the benefits and barriers they encountered when using CBD-only products compared with products containing both CBD and THC.
The findings point to a meaningful difference in patient experience: pain relief was especially prominent among those using CBD+THC products, while participants across the study also reported benefits including improved sleep, physical relaxation, emotional regulation, and reduced use of other medications.
“Introduction: Approximately 20% of cancer patients report cannabis use, yet only 30% of oncologists feel sufficiently informed to make recommendations on its use. This study aimed to visualize the network of themes that arise within cancer patients’ reported experiences with cannabis.
Materials and methods: Data was collected via an online survey of 65 patients who self-reported the use of cannabis in their treatment for cancer, details about the cannabis product(s) being used, their perceived benefits and problems associated with cannabis use, their reasons for starting cannabis use, and any reasons for stopping cannabis use. Epistemic Network Analysis (ENA) was used to compare two groups of cancer patients: 1) those who only used CBD-dominant products (CBD-only group) versus 2) those who used cannabidiol (CBD)- and delta-9-tetrahydrocannabinol (THC)-containing products (either CBD-dominant and THC-dominant cannabis products or cannabis products containing a balanced ratio of both CBD and THC; CBD+THC group).
Results: Cannabis use conferred therapeutic benefits for several health issues commonly encountered by cancer patients. Common benefits reported across the cohort of patients included pain relief, improved sleep, physical relaxation, emotional regulation, and reduction of concomitant medication. The most frequently reported barriers to cannabis use were the stigma associated with THC use and the high cost of CBD-dominant and THC-dominant products. Pain relief emerged as the most prominent, interconnected theme reported by the CBD+THC group, whereas emotional regulation was the most prominent theme for the CBD-only group.
Conclusion: Symptom relief differed based on the cannabinoid composition of the cannabis products. The following trends emerged, which must be confirmed with larger samples: pain relief was more prominent in responses from users of CBD+THC, whereas emotional regulation was more prominent in only the users of CBD-only products. These findings are a step toward assisting cancer patients and providers with clinical decision-making on cannabis use. This study highlights the continued perception of stigma associated with THC use and the need for insurance coverage of medicinal cannabis to reduce the financial burden for this patient population. Finally, this study exemplifies the value of ENA in studying the therapeutic utility of cannabis with qualitative data.”
“Pain relief is more frequently reported among users of CBD+THC products.”
“Emotional regulation is more frequently reported among users of only CBD.”
“Overall, pain relief was the most frequently discussed benefit and was associated with other benefits: emotional regulation, sleep or physical relaxation, and medication reduction. Primary patient concerns were stigma and cost.”
A new study found that cannabidiol (CBD) suppressed glioma growth and reduced tumor-cell migration and invasion in laboratory and animal models. The researchers linked part of this effect to reduced LOXL2 activity, suggesting CBD may interfere with molecular programs that help glioma cells spread into surrounding brain tissue.
The study adds new mechanistic evidence to the growing body of research examining CBD as a potential therapeutic compound in glioma and glioblastoma.
“Background: Gliomas, particularly glioblastoma, remain difficult to control because diffuse infiltration into surrounding brain tissue limits complete resection and contributes to recurrence. Cannabidiol (CBD), a nonpsychoactive cannabinoid capable of entering the central nervous system, has shown antitumor activity in glioma models, but the mechanisms underlying its anti-invasive effects remain unclear. Lysyl oxidase-like 2 (LOXL2) regulates extracellular-matrix remodeling and mesenchymal phenotypes in several cancers. We therefore tested the hypothesis that CBD limits glioma growth and invasion partly by suppressing an LOXL2-associated extracellular-matrix and EMT-like program.
Methods: Human U87 and murine GL261 glioma cells were used to examine CBD effects on tetrazolium-based cell viability, clonogenic growth, cell-cycle progression, apoptosis, migration, and invasion. The two cell lines provided complementary human and murine models, and the immunocompetent intracranial GL261 model enabled syngeneic in vivo validation. RNA sequencing and public glioma datasets were used to identify and contextualize CBD-responsive molecules. Mechanistic involvement was tested by determining whether LOXL2 knockdown phenocopied and LOXL2 overexpression attenuated the anti-invasive effects of CBD.
Results: CBD reduced glioma-cell viability and clonogenicity, induced G1-phase arrest and apoptosis, and suppressed migration and invasion. C CCK-8-derived IC50 values (mean ± SD, n = 3) at 24, 48, and 72 h were 36.5 ± 0.3, 26.7 ± 0.3, and 21.4 ± 0.3 μM in U87 cells and 33.3 ± 0.2, 29.3 ± 0.2, and 25.5 ± 0.4 μM in GL261 cells, respectively. CBD treatment was accompanied by reduced MMP2 and MMP9 expression and increased TIMP3 expression. Transcriptomic profiling identified LOXL2 as a prominent CBD-downregulated molecule, and public datasets associated higher LOXL2 expression with aggressive molecular features and shorter overall survival. LOXL2 silencing reproduced the antimigratory and anti-invasive phenotype, whereas LOXL2 overexpression enhanced cell motility and partially attenuated the effects of CBD. The partial rescue involved vimentin, MMP9/TIMP3, EMT-related transcription factors, and F-actin-rich protrusions. In vivo, CBD reduced intracranial tumor burden and produced tissue changes consistent with lower proliferation, enhanced apoptosis, and suppression of the LOXL2-associated mesenchymal program.
Conclusions: CBD suppresses glioma growth and limits invasion, at least in part, by attenuating an LOXL2-associated EMT-like and extracellular-matrix-remodeling program. Because LOXL2 overexpression produced only a partial rescue and direct target engagement was not tested, LOXL2 should be interpreted as a functional mediator rather than the sole or direct molecular target of CBD. These findings support further validation in patient-derived and pharmacokinetically informed glioma models.”
Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer and remains a major cause of cancer death worldwide.
In a population-based study involving more than 101 million U.S. hospital patients, researchers found a striking association between cannabis use and HCC: after adjusting for multiple potential confounding factors, patients with documented cannabis use were 55% less likely to have hepatocellular carcinoma than patients without documented cannabis use.
The study adds large-scale human observational evidence to earlier preclinical research examining cannabinoids and liver cancer.
“Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and the fourth leading cause of cancer deaths in the world. The association between HCC and cannabis has been identified in mice; however, to our knowledge has not been identified in humans. Therefore, we aim to investigate the relation between HCC and cannabis use in humans.
Methods: Using data from the National Inpatient Sample (NIS) database between 2002 and 2014, we identified the patients with HCC and cannabis use diagnosis using the International Classification of Disease 9th version codes (ICD-9). Then, we identified patients without cannabis use as the control group. We adjusted for multiple potential confounders and performed multivariable logistic regression analysis to determine the association between cannabis abuse and HCC.
Results: A total of 101,231,036 patients were included in the study. Out of the total, 996,290 patients (1%) had the diagnosis of cannabis abuse versus 100,234,746 patients (99%) in the control group without cannabis abuse. We noticed that patients with cannabis abuse were younger (34 vs 48 years), had more males (61.7% vs 41.4%) and more African Americans (29.9% vs 14.2%) compared with the control group (P<0.001 for all). Besides, patients with cannabis use had more hepatitis B, hepatitis C, liver cirrhosis, and smoking, but had less obesity and gallstones, (P<0.001 for all). Using multivariable logistic regression, and after adjusting for potential confounders, patients with cannabis abuse were 55% less likely to have HCC (adjusted Odds Ratio {aOR}, 0.45, 95% Confidence Interval {CI}, 0.42-0.49, P<0.001) compared with patients without cannabis abuse.
Conclusion: Based on our large database analysis, we found that cannabis use patients were 55% less likely to have HCC compared to patients without cannabis use. Further prospective studies are needed to assess the role of cannabis use on HCC.”
This study represents an important part of Olivia Newton-John’s legacy.
After experiencing medicinal cannabis personally during her long cancer journey, Olivia became an outspoken advocate not only for patient access, but for the scientific research needed to determine what cannabis could—and could not—do for people living with cancer.
The Olivia Newton-John Cancer Research Institute later stated that Olivia’s own experience with medicinal cannabis and her interest in pursuing the science behind its use in cancer helped lead the Institute to undertake its first medicinal-cannabis clinical trial.
That work developed into the RESONANCE trial, a Phase I/II double-blind, randomized controlled study examining medicinal cannabis in people with advanced cancer. The study is investigating its effects on quality of life and symptoms including pain, nausea, appetite loss, anxiety and sleep problems, as well as safety and how cannabinoids are metabolized by the body. The study protocol was published in Clinical Therapeutics in 2026.
Olivia repeatedly made clear that her personal experience was not enough. She wanted the science. She wanted researchers to investigate the benefits she believed she had experienced and determine whether other cancer patients could benefit as well.
The study is currently recruiting
As of August 2026, the RESONANCE trial is listed as open and recruiting in Victoria, Australia.
Potential participants may be eligible if they:
are 18 years of age or older;
have advanced cancer; and
have an estimated life expectancy of at least two months.
Additional inclusion and exclusion requirements apply, and final eligibility must be determined by the study team.
Two-thirds of participants receive medicinal cannabis and one-third receive placebo. Both are administered as an oral oil, beginning once daily and increasing, when appropriate, to a maximum of three times per day. Dosing is increased until symptoms are adequately controlled and is then maintained for up to one month. Participants provide blood samples and complete questionnaires, and researchers may also invite a participant’s caregiver to take part in aspects of the study.
After completion of the trial period, participants may be able to obtain medicinal cannabis through compassionate access.
Clinical trial registration: ACTRN12619001534178.
Interested in participating?
People interested in the trial should discuss participation with their doctor and contact the research center to determine whether they meet the complete eligibility requirements. Peter MacCallum Cancer Centre currently lists the study as open and recruiting and directs prospective participants to the full Australian clinical-trial registry criteria.
Dr. Jodie Palmer Olivia Newton-John Cancer Research Institute Level 5, ONJWRC 145 Studley Road Heidelberg, Victoria 3084, Australia Phone: +61 3 9496 3573 Email:trials@onjcri.org.au
Olivia spent the final years of her life asking that medicinal cannabis be taken seriously enough to study scientifically. She believed her own experience raised questions worth answering.
This study is part of the scientific legacy she helped set in motion.
“Purpose: Medicinal cannabis is increasingly used in cancer care despite limited high-quality evidence to inform practice. It is increasingly legalized around the world; however, this has outpaced high-quality research on cancer symptom outcomes, leading to patient and prescriber uncertainty. This trial evaluates the safety profile, tolerability, and impact of medicinal cannabis on quality of life in advanced cancer.
Methods: This is a Phase I/II multicenter clinical trial. The Phase I component is open-label and aims to determine the safety profile and tolerability of medicinal cannabis use by evaluating clinical outcomes and pharmacokinetic profile. The Phase II component is a double-blind, randomized clinical trial that aims to determine the impact of medicinal cannabis on quality of life and symptom control (pain, anorexia, anxiety, sleep, nausea, treatment satisfaction, toxicity, and caregiver burden) using validated instruments in people with advanced cancer.
Findings & implications: This trial is expected to generate important knowledge about the tolerability, efficacy, and adverse effects of medicinal cannabis in people with advanced cancer, with a particular focus on quality of life and symptom burden. Protocol adaptations aimed at enhancing inclusivity may be worth noting in future studies. Collectively, the findings have the potential to inform clinical practice, reduce decisional uncertainty among prescribers and patients, and affect care for the estimated 10 million people who die of advanced cancer annually worldwide. Australian New Zealand Clinical Trials Registry identifier: ACTRN12619001534178.”
Glioblastoma remains one of the most difficult brain cancers to treat, in part because tumor cells can develop resistance to chemotherapy. In laboratory testing, combinations of the minor cannabinoids CBN or CBG with melatonin produced synergistic anticancer effects against human glioblastoma cells while sparing healthy astrocytes, and significantly enhanced the effectiveness of temozolomide.
“The prognosis of glioblastoma (GBM) patients remains dismal due to chemoresistance.
Repurposing of natural and endogenous compounds, such as the pineal hormone melatonin (MLT) and minor phytocannabinoids like cannabinol (CBN) or cannabigerol (CBG), represents a promising strategy.
This study investigates the cytotoxic potential of combining these phytocannabinoids with MLT, evaluating their efficacy both alone and synergistically with temozolomide (TMZ) to overcome drug resistance.
To achieve this, cytotoxicity, synergy (Bliss model), and selectivity were evaluated in U87, T98, and U251 GBM lines and normal astrocytes. Mechanisms of damage were characterized via Western blot (γH2AX and PARP-1), flow cytometry using fluorescent dyes/probes (DCFDA, JC-1, MitoBright, BODIPY, PI, and Annexin-V), or the protein marker COX IV and confocal analysis.
The results demonstrated that CBN-MLT and CBG-MLT regimens exerted synergistic cytotoxicity while sparing healthy astrocytes. Notably, combining these regimens (U87: MLT 0.3 mg/mL + CBN 25 µM; MLT 0.2 mg/mL + CBG 15 µM. T98: MLT 0.7 mg/mL + CBN 25 µM; MLT 0.6 mg/mL + CBG 30 µM. U251: MLT 0.4 mg/mL + CBN 20 µM; MLT 0.5 mg/mL + CBG 35 µM) with TMZ significantly enhanced chemotherapeutic efficacy, overcoming baseline effects of TMZ in these cell lines.
The combinations induced necrotic cell death characterized by severe double-strand DNA damage. This was driven by an early accumulation of intracellular ROS, which triggered mitochondrial depolarization, loss of organelle mass, and lipid peroxidation. CBN combinations consistently triggered more robust biochemical alterations than CBG-based treatments.
Taken together, this study provides a strong preclinical basis for utilizing minor cannabinoids combined with MLT in GBM management.
Crucially, this co-treatment emerges as a promising approach to potentiate TMZ efficacy, offering a novel and potentially effective therapeutic strategy to counter GBM resilience.”
“In recent years, the repurposing of endogenous compounds and natural products has emerged as a promising frontier in neuro-oncology. Among these, the pineal hormone melatonin (MLT) and phytocannabinoids derived from Cannabis sativa, most notably Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), have shown strong individual anti-cancer effects “
“Crucially, phytocannabinoids are capable of inhibiting tumor growth, inducing cancer cell death, and modulating the immune microenvironment. Moreover, they have demonstrated a distinct ability to enhance the effectiveness of conventional therapies and sensitize chemotherapeutic treatments, helping to overcome established resistance mechanisms.”
High-grade glioma is marked by aggressive growth, inflammation, and oxidative stress, creating a need for therapies that can target several tumor-supporting pathways at once. In this preliminary in vivo study, liposomes carrying cannabidiol (CBD) and celecoxib modulated inflammatory and redox signaling in glioma tissue and showed antitumor effects. The researchers concluded that this combined liposomal approach may represent a promising strategy for further development against high-grade glioma.
“Inflammation contributes to the rapid progression of high-grade gliomas, indicating that anti-inflammatory strategies targeting NF-κB signaling may offer therapeutic benefit.
Cannabidiol (CBD) and celecoxib (CELE) are hydrophobic pharmacological agents whose formulation in lipid carriers may support their combined biological evaluation.
In this proof-of-concept study, we investigated liposomal formulations containing CBD, CELE, or both compounds in U-87 MG high-grade glioma cells and in a subcutaneous xenograft model.
We assessed cytotoxicity, apoptosis, oxidative stress, Nrf2-dependent responses, NF-κB-centered inflammatory networks, tumor cell invasive properties, and Wnt/β-catenin pathway activity. The nanoformulations induced reactive oxygen species generation by 1.8-fold, which was accompanied by Nrf2 activation. Cationic formulations loaded with the compounds produced more pronounced pro-apoptotic effects (up to 39%) than POPC liposomes, although both types reduced the nuclear translocation of the NF-κB p65 subunit.
The CBD + CELE-containing formulation showed a trend toward reduced tumor progression in mice. It is important to note that the in vitro and in vivo nanoformulations were physicochemically related, but not identical, and the in vivo experiment should be interpreted as a preliminary assessment after intratumoral administration.
Overall, cationic liposomes co-loaded with CBD + CELE represent a promising platform for further optimization aimed at coordinated modulation of inflammatory, oxidative, and proliferative pathways in glioma. However, additional studies, including tissue distribution, release kinetics, and efficacy in orthotopic glioma models, are needed to fully verify their translational potential.”
“In summary, this study shows that liposomal formulations containing CBD and CELE, particularly DOTAP:POPC formulations prepared with both compounds, modulate apoptosis, cell cycle distribution, oxidative stress, Nrf2/NF-κB/Wnt-related pathways, and glioma-associated inflammatory mediators in U-87 MG-based models. In the subcutaneous xenograft model, intratumoral administration of the CBD + CELE-containing formulation was associated with a trend toward reduced tumor progression and modulation of selected tumor-associated proteins.”
Cholangiocarcinoma is an aggressive bile duct cancer in which chemoresistance remains a major treatment challenge. In human cholangiocarcinoma cells, CBD, CBG, and CBN each produced dose-dependent anticancer effects, suppressing proliferation, reducing Ki67 expression, disrupting mitochondrial function, and inducing apoptosis; all three showed lower IC50 values than cisplatin and activity comparable to gefitinib. The researchers concluded that these cannabinoids show potential for development as cannabinoid-based therapeutic strategies for cholangiocarcinoma.
“Background: Chemoresistance remains a major obstacle in managing cholangiocarcinoma (CCA). The cannabis plant contains several phytocannabinoids, including cannabidiol (CBD), cannabigerol (CBG), and cannabinol (CBN), which exhibit anticancer properties. However, to the best of our knowledge, their effects on CCA have not been previously investigated. This study aimed to explore the molecular mechanisms underlying the anticancer effects of CBD, CBG, and CBN in CCA cells.
Methods: KKU-100 and KKU-452 cells were treated with varying concentrations of CBD, CBG, and CBN for 24 and 48 h. Cytotoxicity was assessed using the MTT assay, and half maximal inhibitory concentration (IC50) values were calculated. KKU 452 cells were further analyzed for apoptosis, mitochondrial membrane potential (MMP), and Ki67 expression using flow cytometry. Proteomics profiling was performed to compare the effect of these cannabinoids with those of gefitinib and cisplatin.
Results: Monotherapy with CBD, CBG, or CBN induced dose-dependent cytotoxicity at 24 and 48 h with lower IC50 values than those of cisplatin and comparable efficacy to that of gefitinib. At low doses, CBD, CBG, and CBN induced early apoptosis, while higher doses triggered late apoptosis. MMP loss increased by 2.5-, 4.9-, and 1.7-fold, respectively, after 6 h. Ki67, highly expressed in KKU-452 cells (Ki67-positive ratio = 3.16 ± 0.16), was significantly reduced after the cannabinoid treatment, with Ki67-positive ratios of 0.38 ± 0.22, 0.38 ± 0.13, and 0.32 ± 0.23 for CBD, CBG, and CBN, respectively. Proteomics analysis identified 2781 proteins affected by CBD, CBG, CBN, cisplatin, and gefitinib. All three cannabinoids downregulated key upstream regulatory proteins (LARP1, TFEB, and BCR). Similar patterns of LARP1 and TFEB downregulation were also observed with cisplatin and gefitinib. CBN showed the closest similarity to cisplatin, followed by gefitinib, by targeting CDK4/6 and PCGEM1 proteins. CBD and CBG exhibited the greatest similarity to each other, also influencing MASTL expression.
Conclusions: CBD, CBG, and CBN exhibit potential anticancer activity in CCA by suppressing proliferation, reducing Ki67 expression, and inducing apoptosis through MMP disruption. The identification of shared molecular targets, including LARP1 and TFEB, provides new mechanistic insight and supports the potential development of cannabinoid-based therapeutic strategies for cholangiocarcinoma.”
Estrogen receptor-positive breast cancer remains one of the most common forms of breast cancer, and new adjunctive treatment strategies are still needed. In this mouse xenograft study, a whole-cannabis extract containing THC and CBD in a 1:6 ratio significantly suppressed tumor growth, reduced tumor-cell proliferation, and increased apoptosis-related changes, with the highest dose producing the greatest reduction in tumor volume. The researchers concluded that the extract showed promising antiproliferative and antitumor activity and may warrant further investigation as an adjunctive approach for ER-positive breast cancer.
“Background and aim: Breast cancer remains one of the leading causes of cancer-related mortality worldwide, despite advances in surgery, chemotherapy, endocrine therapy, and targeted treatments. Cannabinoids derived from Cannabis sativa, particularly tetrahydrocannabinol (THC) and cannabidiol (CBD), have demonstrated anticancer properties in several experimental models; however, in vivo evidence in estrogen receptor (ER)-positive breast cancer remains limited. This study aimed to evaluate the antitumor effects of a THC:CBD (1:6) cannabis extract in a Michigan Cancer Foundation-7 breast cancer cell line (MCF-7) xenograft mouse model of ER-positive breast cancer.
Materials and methods: Female BALB/c nude mice bearing MCF-7 xenograft tumors were randomly assigned into five groups (n = 5/group): negative control (sesame oil), positive control treated with 5-fluorouracil (5-FU; 20 mg/kg), and three treatment groups receiving oral THC:CBD (1:6) extract at doses of 2, 10, or 20 mg/kg body weight for 30 consecutive days. Tumor growth was monitored throughout the experiment. Histopathological examination and immunohistochemical analysis of proliferating cell nuclear antigen (PCNA) expression were performed to evaluate apoptosis-related morphology and tumor cell proliferation. Hematological and biochemical parameters were assessed to determine systemic safety.
Results: Cannabinoid-treated groups exhibited significant suppression of tumor growth compared with the negative control group. Tumor volume reduction was observed in all treatment groups, with the greatest reduction detected in the high-dose THC:CBD group. Histopathological evaluation revealed increased numbers of tumor cells exhibiting morphological features consistent with apoptosis in cannabinoid-treated mice. Immunohistochemical analysis demonstrated significantly lower PCNA expression scores in all THC:CBD-treated groups compared with both negative and positive controls, indicating reduced tumor cell proliferation. Hematological parameters remained within normal physiological ranges in cannabinoid-treated animals. However, elevated alanine aminotransferase and aspartate aminotransferase levels were observed in the high-dose group, suggesting potential dose-related hepatic stress.
Conclusion: The THC:CBD (1:6) cannabis extract demonstrated significant antitumor activity in an MCF-7 xenograft model by suppressing tumor progression primarily through inhibition of tumor cell proliferation, with supportive apoptosis-related histological features. These findings provide novel in vivo evidence supporting the potential of cannabinoid-based formulations as adjunctive therapeutic approaches for ER-positive breast cancer.”
“In conclusion, the present study demonstrated that the THC:CBD (1:6) whole-cannabis extract exerted significant antitumor activity in an MCF-7 xenograft model of ER-positive breast cancer. Treatment with the cannabinoid extract resulted in marked suppression of tumor growth, significant reduction in tumor volume, decreased PCNA expression, and increased numbers of tumor cells exhibiting apoptosis-related morphological features.
Among the tested doses, the high-dose THC:CBD group showed the greatest reduction in tumor volume, indicating a strong antiproliferative effect of the cannabinoid formulation.”
“Overall, despite the inherent limitations of xenograft models, the present findings indicate that the THC:CBD (1:6) cannabis extract possesses promising antiproliferative and antitumor properties in ER-positive breast cancer. These results provide a foundation for future mechanistic and translational studies exploring cannabinoids as potential adjunctive agents in breast cancer therapy.”
