Category Archives: Cancer

Exosomal cannabidiol: A promising candidate for targeted oral delivery against breast cancer

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“Breast cancer (BCa) remains a leading cause of cancer-related deaths in women worldwide. Triple-negative BCa (TNBC) is highly metastatic with treatment limited by off-target toxicity.

Cannabidiol (CBD) has anti-cancer and anti-inflammatory activity in BCa.

This study addresses the poor oral bioavailability of CBD by utilizing exosomes (Exo) as a drug delivery system.

CBD was loaded onto non-functionalized exosomes and folic acid-functionalized exosomes (FA-Exo), achieving an average CBD drug load of ∼20%. The FA-ExoCBD averaged 136 ± 2.9 nm in size. TNBC cell lines MDA-MB-231 and taxol-resistant MDA-MB-231TR were sensitive to growth inhibition by CBD than estrogen receptor positive (ER+) MCF-7 and its taxol-resistant derivative MCF-7TR. Exosomal formulations (ExoCBD and FA-ExoCBD) demonstrated time-dependent CBD release under physiologically relevant simulated gastric and intestinal conditions and withstand acidic conditions, retained canonical exosomal markers (CD81 and Alix) as well as physical parameters of exosomes including size, PDI and zeta potential.

CBD downregulated key anti-apoptotic and anti-inflammatory markers.

Oral FA-ExoCBD showed enhanced tumor targeting, tumor retention and inhibition of orthotopic MDA-MB-231-tumor growth in NOD Scid mice than ExoCBD or free CBD. RNA-Seq analysis of tumor tissues revealed that both CBD and FA-ExoCBD treatments modulated over 1000 genes, with FA-ExoCBD significantly downregulating IL13RA2 (associated with lung metastasis) and tumor biomarkers TRPM2 and SAMHD1, while upregulating tumor suppressors PRDM1, PCDHGB2, and ICAM1.

These findings highlight the potential of FA-ExoCBD to enhance CBD’s anticancer efficacy through targeted gene modulation. Overall, FA-ExoCBD improves CBD’s therapeutic profile by enhancing efficacy, tumor selectivity, improved bioavailability and anticancer efficacy.”

https://pubmed.ncbi.nlm.nih.gov/41812824

https://www.sciencedirect.com/science/article/abs/pii/S0304383526001795?via%3Dihub


Potential of Using Cannabidiol as a Therapeutic Molecule Against Various Cell Signaling Molecules Involved in Breast Cancer Complications: A Bioinformatics Approach

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“Background: Breast cancer progression involves key processes such as uncontrolled cell proliferation, resistance to apoptosis, metastasis, and angiogenesis. Cannabidiol (CBD), a non-psy-choactive compound from Cannabis sativa, has shown promise for its anti-cancer properties. This study aimed to explore the interaction of CBD with proteins involved in these processes.

Methods: Molecular docking was performed to assess the binding affinity of CBD to four critical proteins: CDK6 (cell cycle regulator), BCL2 (anti-apoptotic protein), MMP2 (invasion-related en-zyme), and VEGFR2 (angiogenesis-related receptor). Known inhibitors, palbociclib, ABT-199, doxycycline, and axitinib, were used as reference compounds for comparison.

Results: Cannabidiol exhibited strong binding affinities for CDK6, BCL2, MMP2, and VEGFR2. The docking scores were comparable to those of the respective standard inhibitors, suggesting effec-tive interactions with the active sites of the target proteins.

Discussion: These findings suggest that CBD may simultaneously target multiple cancer-related pathways, offering a potential multi-target therapeutic approach for breast cancer. Its comparable efficacy to standard inhibitors, combined with a favorable safety profile, supports its potential for further development. However, experimental validation through in vitro and in vivo studies is neces-sary to confirm its therapeutic effectiveness.

Conclusion: CBD demonstrates promising multi-target activity against critical signaling molecules in breast cancer and may serve as a safer, natural therapeutic candidate. Further preclinical and clin-ical investigations are warranted.”

https://pubmed.ncbi.nlm.nih.gov/41830580

https://www.eurekaselect.com/article/153254

Quantitative analysis of Cannabinoid Therapy in Prostate Cancer: Integrating Biomarkers, Imaging and Patient Outcomes

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“Cannabinoids are increasingly used by cancer patients for symptom relief, yet clinical evidence on their effect in prostate cancer remains limited. This study evaluated the association between cannabinoid therapy and disease activity, pain, and quality of life in men with prostate cancer.

The objectives were to assess the influence of cannabinoids on PSA levels, metabolic activity, tumour size via PET/CT scans, and patient-reported outcomes including pain levels and quality of life.

Methods: Ninety men with confirmed prostate cancer were prospectively followed in three groups: chemotherapy-only, cannabis-only, and combined chemotherapy + cannabis. PSA, PET/CT findings, and patient-reported outcomes (BPI, EQ-5D) were assessed at baseline, 3 months, and 6 months. Longitudinal changes were analysed using linear mixed-effects regression with group × time interactions, and between-group differences were tested with ANOVA. PET/CT categorical outcomes were evaluated using multinomial logistic regression to generate adjusted odds ratios

Results: Significant temporal differences in PSA levels were detected among groups (p < 0.001); both cannabis-containing regimens showed faster PSA decline, but final values were comparable across treatments. PET/CT analyses indicated a higher likelihood of remission or tumour reduction in the combined group (p = 0.013).

Cannabis use, alone or combined was associated with greater reductions in pain and improved emotional well-being compared with chemotherapy alone, while improvements in self-care and usual-activity scores were also observed.

Conclusion: Cannabinoid therapy, whether used independently or alongside chemotherapy, was associated with improved pain control and some indicators of tumour response, without evidence of harm. The findings warrant cautious interpretation and support further randomized studies to clarify cannabinoids’ adjunctive role in prostate cancer management.”

https://karger.com/mca/article/doi/10.1159/000550792/946276/Quantitative-analysis-of-Cannabinoid-Therapy-in

Hemp-Derived Extracellular Vesicles: A Novel Frontier in Nanomedicine and Therapeutics

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“While mammalian-derived extracellular vesicles (EVs) face significant challenges in clinical translation due to scalability, cost, and safety, plant-derived EVs (PDEVs) have emerged as a promising alternative.

This review focuses on EVs derived from hemp (Cannabis sativa L.), or HEVs, a particularly compelling source that combines the general benefits of PDEVs, such as improved safety and scalability, with a unique, inherent therapeutic cargo.

HEVs are naturally enriched with a potent mix of cannabinoids, terpenes, and flavonoids, which may enhance therapeutic outcomes through synergistic interactions-a phenomenon known as the ‘entourage effect.’

Preclinical studies already demonstrate their potential, showing significant anti-cancer effects against aggressive tumors like glioblastoma, along with neuroprotective and anti-inflammatory properties.

However, the critical challenge hindering their clinical application is the lack of standardized, GMP (Good Manufacturing Practice)-compliant manufacturing protocols to address the inherent biochemical variability of the source material.

Overcoming these obstacles will be vital to unlocking the potential of HEVs as a novel, scalable frontier in nanomedicine.”

https://pubmed.ncbi.nlm.nih.gov/41787227

https://link.springer.com/article/10.1007/s40259-026-00766-0

Cannabidiol-induced cellular and matrix-associated responses in primary equine sarcoid cells

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“Background: Sarcoids are locally invasive skin tumors in equids, associated with bovine papillomavirus.

Hypothesis/objectives: Address potential applications of cannabidiol (CBD) in veterinary medicine. We evaluated the response of equine sarcoid cells to CBD in vitro, focusing on viability, invasiveness, and matrix remodeling.

Animals: Three primary sarcoid cell lines.

Methods: Cells were treated with CBD (20, 6.75, 2.25, 0.75 μM) and incubated for 6, 24, 48, 72 hours. Cell viability, cytotoxicity, and apoptosis were assessed using the ApoTox-Glo Assay. Based on these results, further analyses were performed for selected conditions only, including the assessment of cell invasiveness using the ECMatrix™ Cell Invasion Assay and the quantification of matrix metalloproteinase (MMP)-1, -2, and -9 in the culture medium by ELISA.

Results: Treatment with CBD affected cell viability, cytotoxicity, and apoptosis. At 48 hours, apoptosis (measured as caspase 3/7 activity) reached 49.5% and further increased to 75% at 72 hours. Marked cytotoxicity (>96%) and decreased viability were observed at 72 hours. Cannabidiol also significantly decreased MMP-1 concentration by 48.9% at 24 hours and MMP-2 concentrations by 84% at 6 hours. Concentrations of MMP-9 also decreased by 37.2% and 45.3% at 6 and 48 hours, respectively, after treatment with 20 μM. Despite observed decreases in cell invasiveness ranging from 34% to 59% after 24 hours, these changes were not significant.

Conclusions and clinical importance: Our findings support further investigation of CBD’s role in extracellular matrix modulation in sarcoid tumors.”

https://pubmed.ncbi.nlm.nih.gov/41742517

“Overall, equine sarcoid cells exhibit clear biological responsiveness to CBD, supporting its relevance as a modulator of matrix remodeling and invasive potential in this tumor model.”

https://academic.oup.com/jvim/article/40/1/aalaf015/8429746?login=false

Potential therapeutic role of Cannabidiol and vitamin D in Hepatocellular carcinoma: evidence from in vitro studies

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“Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide, underscoring the need for novel therapeutic strategies. Natural compounds with anticancer properties have gained increasing attention.

Cannabidiol (CBD) and Vitamin D have individually been reported to exert anti-proliferative and pro-apoptotic effects in various cancer models.

Methods and results

The effects of Vitamin D and CBD, alone and in combination, were investigated in two human HCC cell lines, Hep3B and Huh7. Cell viability was assessed using MTS assays, and drug interactions were evaluated by the Chou–Talalay method. Apoptosis, cell cycle progression, and molecular changes related to apoptosis, autophagy, cell proliferation, and DNA damage response were analyzed by flow cytometry and real-time PCR. Combined treatment with Vitamin D and CBD resulted in a synergistic reduction in cell viability in both cell lines, with lower IC₅₀ values compared to single treatments. The combination enhanced apoptotic signaling and inhibited cell proliferation in a cell line–dependent manner. In Hep3B cells, combined treatment induced G1 phase arrest, modulation of autophagy-related genes, and alterations in DNA damage response pathways, whereas Huh7 cells exhibited distinct transcriptional responses.

Conclusions

These findings demonstrate that the combination of Vitamin D and CBD exerts enhanced anticancer effects in HCC cells in vitro. This study provides mechanistic insight supporting further investigation of Vitamin D and CBD as a potential combinatorial therapeutic approach for HCC.”

https://link.springer.com/article/10.1007/s11033-026-11555-x

Cannabinoids and the autophagy-related signaling in brain Tumors: From mechanistic insights to therapeutic Frontiers in glioblastoma

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“Glioblastoma multiforme (GBM) is a very aggressive primary brain tumor in adults, characterized by extensive infiltration, therapeutic resistance, and a dismal prognosis, with an average life of roughly 14 months. Despite advances in oncology, therapeutic progress for GBM has been limited, prompting intensive efforts to discover novel interventions.

Cannabinoids, beyond their established role as antiemetics during chemotherapy and radiotherapy, have emerged as potential cytotoxic agents against neoplastic cells.

Recent studies demonstrate that GBM harbors alterations in the endocannabinoid system, including changes in cannabinoid metabolism and receptor (CB1R, CB2R) expression. Engagement of these receptors by cannabinoids can suppress proliferation, invasion, and induce morphological changes in GBM cells, also activating intrinsic autophagy pathways.

Autophagy, a process central to cellular degradation and recycling, exerts dual roles in tumor survival and apoptosis, critically modulated by cannabinoids in glioblastoma. Preclinical work in cell lines and animal models suggests that both cannabinoids and pharmacologic modulators of autophagy reduce GBM proliferation and enhance responsiveness to chemotherapeutics. Early clinical studies indicate favorable safety profiles and potential survival benefits.

This review synthesizes the molecular mechanisms and signaling pathways underlying cannabinoid-induced autophagy and anticancer activity, and summarizes the current preclinical and clinical research on cannabinoid-based therapies for GBM.”

https://pubmed.ncbi.nlm.nih.gov/41679657

“This review demonstrates that cannabinoids, an emerging class of potential antitumor agents, promote autophagy in cancer cells and enhance the cytotoxic effects of these compounds. The study demonstrated that THC facilitates autophagy and apoptosis in diverse cancer cell types, whereas nontransformed astrocytes display resistance to cannabinoid-induced cytotoxicity. “

https://www.sciencedirect.com/science/article/abs/pii/S0006295226001127?via%3Dihub


Pharmacokinetic studies and synergistic antitumor effects of cannabichromene and cannabidiol in drug-resistant breast cancers

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“Triple-negative breast cancer (TNBC) is highly aggressive with limited treatment options, and resistance to doxorubicin (DOX) further compromises outcomes.

Cannabinoids such as cannabichromene (CBC) and cannabidiol (CBD) possess anticancer properties, but their combined effects in resistant TNBC remain unexplored. This study evaluated the antitumor efficacy of a CBC + CBD combination against DOX-resistant (DOX-RT) TNBC using in vitro, in vivo, and pharmacokinetic models.

Cytotoxicity was assessed in DOX-RT MDA-MB-231 cells using 2D and 3D assays, with synergy confirmed by combination index (CI) analysis. Cell cycle and invasion assays were performed. Xenograft studies were conducted in BALB/c nude mice bearing DOX-RT tumors treated intraperitoneally with CBC (10 mg/kg), CBD (20 mg/kg), or CBC + CBD. Pharmacokinetics were evaluated in rats, complemented by GastroPlus™ simulations.

CBC + CBD synergistically inhibited cell growth induced G0/G1 arrest, and reduced invasiveness by ~ 55% in a Transwell Matrigel invasion assay. In xenografts, combination therapy reduced tumor volume by two-folds compared to single treatments and fourfolds versus control. Western blotting revealed downregulation of MEK/ERK, PI3K/AKT/mTOR, Cyclin D1, CDK6, SOD2, and NF-κB. Pharmacokinetic studies showed co-administration increased Cmax and AUC without altering Tmax, supported by simulations predicting enhanced jejunal absorption. CBC + CBD co-therapy demonstrates synergistic efficacy against resistant TNBC by inhibiting oncogenic pathways and enhancing systemic exposure.

This first study of its kind highlights CBC + CBD as a promising strategy to overcome DOX resistance in TNBC.”

https://pubmed.ncbi.nlm.nih.gov/41670942

https://link.springer.com/article/10.1007/s13346-026-02057-1

Cannabidiol modulates exosomal miRNA networks to enhance Imatinib mesylate response in chronic myelogenous leukemia

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“Background/objectives: Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disease driven by the BCR-ABL1 fusion oncogene. Tyrosine kinase inhibitors (TKIs) such as Imatinib mesylate have dramatically improved patient outcomes, yet resistance remains a major obstacle to long-term efficacy. Exosomes, as carriers of bioactive molecules including miRNAs, are increasingly recognized as mediators of drug resistance. CBD has demonstrated antiproliferative and pro-apoptotic effects in several cancer models, but its potential to modulate Imatinib sensitivity or resistance in CML remains unclear. This study aimed to investigate exosomal miRNA signatures associated with Imatinib sensitivity and resistance in the context of treatment with Cannabidiol (CBD), Imatinib mesylate (IM), and their combination.

Methods: Following treatment with CBD, IM, and CBD+IM, exosomal miRNA profiles in Imatinib-sensitive (K-562S) and Imatinib-resistant (K-562 R) cell lines were analyzed. Gene Ontology (GO) enrichment and semantic clustering was performed.

Results: CBD activated tumor-suppressive and apoptosis-related miRNAs in K-562S cells, whereas K-562 R cells showed a dual response involving oncogenic miRNAs and metabolic regulators. IM induced suppressive cascades in K-562S but caused loss of canonical tumor suppressors in K-562 R. CBD+IM produced synergistic amplification of apoptotic and differentiation-related pathways in sensitive cells, while resistant cells showed partial restoration of apoptosis but persistent loss of tumor suppressors. HMGB1-associated miRNAs were identified, of which suppressed were miR-615-5p, miR-4435, let-7 g-3p, and the miR-548 family, alongside upregulated miR-3191-3p and miR-33a-5p.

Conclusions: Circulating miRNAs are valuable biomarkers for TKI resistance in CML. Targeting HMGB1-associated miRNAs, together with combined CBD and IM treatment, may help re-establish apoptotic regulation and overcome resistance mechanisms.”

https://pubmed.ncbi.nlm.nih.gov/41657764

https://www.sciencedirect.com/science/article/pii/S2699940426000020?via%3Dihub

Hemp seed extract exerts cytostatic effects through metabolic stress and autophagy modulation in malignant cells

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“Phytocannabinoids from Cannabis sativa L. exhibit anticancer activity, but how the polar fraction from cold-pressed hemp seed oil derived from industrial cultivars lacking Δ9-THC affects cell proliferation remains unclear.

Here, we characterized the phenolic composition of the Oil Polar Extract (OPE) from the Codimono cultivar and evaluated its effects on cancer cells. In HT-29 colorectal cells, OPE induced metabolic stress, decreasing ATP by ~ 40%, activating AMPK, and disrupting autophagic flux. This stress led to G1 phase cell cycle arrest without triggering apoptosis.

Notably, pharmacological inhibition of autophagy with chloroquine enhanced the antiproliferative effects of the extract by ~ 30%, indicating that autophagy serves a cytoprotective role.

These findings identify OPE as a metabolic modulator capable of inducing an AMPK-dependent cytostatic effect in colorectal cancer cells, supporting its potential as a non-psychotropic, plant-derived anticancer strategy and as a candidate for combination therapies with autophagy inhibitors.”

https://pubmed.ncbi.nlm.nih.gov/41620507

https://www.nature.com/articles/s41598-026-37119-4