Category Archives: Cancer

Hemp-Derived Iron Oxide Nanoparticles for Biomedical Applications: Synthesis, Characterization, and Therapeutic Potential

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“Iron oxide nanoparticles (IONPs) have emerged as the most widely synthesized metal nanoparticles in sustainable chemistry due to their unique magnetic properties, excellent biocompatibility, biodegradability, and non-toxicity.

In this study, IONPs are successfully synthesized via a rapid, sustainable, and environmentally friendly green synthesis approach using Cannabis sativa L. leaf extract. X-ray diffraction analysis determined that the synthesized NPs had an average particle size of 18.8 nm, while transmission electron microscopy images reveal a spherical morphology with sizes ranging from 12 to 21 nm.

Fourier-transform infrared spectroscopy analysis confirmed the presence of cannabinoids, terpenoids, and flavonoids, which are believed to play a crucial role in the formation and stabilization of IONPs. Its photocatalytic potential is demonstrated through the degradation of bromophenol blue dye.

Additionally, the NPs exhibited significant antibacterial and antifungal activity against various microbial species, along with promising anticancer effects on cancer cell lines.

In conclusion, this study provides a promising foundation for advancing the large-scale, commercial production of IONPs through green synthesis methods. By offering an eco-friendly and efficient alternative to conventional nanoparticle synthesis, the findings contribute significantly to the growing body of research in sustainable nanotechnology.”

https://pubmed.ncbi.nlm.nih.gov/40525672/

“In this study, IONPs were successfully synthesized via a single-step green approach using C. sativa leaf extract as the sole reducing and stabilizing agent, eliminating the need for secondary chemicals. Collectively, these findings underscore the potential of eco-friendly IONPs for biomedical and environmental applications, aligning with sustainable nanotechnology paradigms.”

https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/open.202500189

Revealing the therapeutic potential of synthetic cannabinoids: a systematic review of cannabinoid receptor binding dynamics and their implications for cancer therapy

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“Background: Cancer remains a major global health issue, prompting the need for innovative treatment approaches that extend beyond conventional methods such as chemotherapy and radiation. The endocannabinoid system (ECS), primarily the cannabinoid receptors CB1R and CB2R, presents a promising opportunity for cancer therapy by selectively targeting cell signaling pathways. This systematic review intends to explore the mode of action of synthetic cannabinoids as potential anticancer agents and their impact on tumor growth in various cancer cell lines.

Methods: Of the 287 articles identified between January 1990 and July 2024, 27 studies met strict criteria focusing on their anticancer effects. Data extraction and quality assessment were conducted using GRADE criteria and the Cochrane Risk of Bias tool, ensuring robust evaluation of the studies’ reliability.

Results: Various pharmacological actions of synthetic cannabinoids function as agonists, antagonists, and inverse agonists at the CB1R and CB2R receptors. Key findings indicate that CB2R agonists significantly reduce cancer cell proliferation through diverse mechanisms, with selective CB2R agonists effectively inhibiting cancer cell growth and survival. Studies involving CB1R antagonists, particularly in conjunction with CB2R agonists, highlight their role in blocking CB1R to either validate or enhance the efficacy of CB2R agonists in mitigating tumor growth. Inverse agonists targeting CB2R have shown moderate success in inducing cancer cell death by disrupting survival pathways. Notably, synthetic cannabinoid agonists display significant potential in targeting CB1 and CB2 receptors to inhibit tumor proliferation and promote apoptosis across various cancer types.

Conclusion: The systematic review concludes that CB2R agonists can effectively inhibit tumor growth while inducing apoptosis in various cancers. Although CB1R agonists show potential in modulating cancer pathways, there is a notable lack of research on CB1 inverse agonists, emphasizing the need for further investigation. Additionally, the study advocates for greater exploration of mixed receptor agonist and receptor mode of action to validate these promising therapeutic approaches.”

https://pubmed.ncbi.nlm.nih.gov/40483537/

“Phytocannabinoids, which are the natural cannabinoids found in Cannabis sativa, have been extensively studied for their potential anticancer effects. These compounds act as agonists for cannabinoid receptor 1 and cannabinoid receptor 2, facilitating their therapeutic applications through the activation of these CBRs. By activating CB1R and CB2R, phytocannabinoids produce various therapeutic effects, including anti-nociception, anti-inflammation, anticonvulsant, and anti-emetic properties.”

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-025-00289-5

CBD promotes antitumor activity by modulating tumor immune microenvironment in HPV associated head and neck squamous cell carcinoma

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“Introduction: Marijuana use is associated with HPV-positive head and neck squamous cell carcinoma (HNSCC). However, cannabinoid use continues to increase in the US general population for recreational purposes as well as in cancer patients for palliative care. In this study, we explored the role of cannabidiol (CBD) in promoting anti-tumor activity by modulating immune response in HPV-positive HNSCC by using pre-clinical models.

Methods: The anti-proliferative effect of CBD on HPV-positive HNSCC cells was evaluated through BrdU, apoptosis and migration analyses, followed by western blot analysis to assess its role in activating the MAPK pathway. Next, the anti-tumor immune response of CBD was evaluated in immunocompetent syngeneic mouse as well as in immune-deficient B6.129S7-Rag1tm1Mom/J or Rag 1 Knockout mice (Rag1 -/-) and athymic nude mouse. Immune cell infiltration was measured by flow cytometry, IHC and multiplex IHC analysis after subcutaneous injection of mEER cells. Furthermore, the anti-tumor activity of CBD on the tumor microenvironment was evaluated after the depletion of CD4+T cells and CD8+T cells in murine models.

Results: We observed CBD treatment inhibited cell proliferation and migration by promoting apoptosis in HPV-positive HNSCC cells through activation of the MAPK pathway and its associated markers like ERK1/2, JNK/SAPK and MK2. CBD significantly inhibited tumor growth in immunocompetent mice but had no effect in immune-deficient models, indicating an immune-dependent mechanism. CBD enhanced infiltration of CD4+T and CD8+T cells, CD19+B cells, NK cells, and M1-like macrophages into the primary tumors of immunocompetent syngeneic mice models, implicating an enhanced anti-tumor immune response. Interestingly, we observed a significant increase in tumor volume in CD4-depleted mice treated with CBD as compared to CBD-treated wild-type mice suggesting the importance of CD4+T cells in CBD-mediated anti-tumor activity. Finally, multiplex IHC analysis demonstrated co-localization of CD4+T and CD8+ T cells with the activated MAPK marker phospho-p38 in CBD-treated tumors.

Discussion: CBD inhibits tumor cell proliferation in HPV-positive HNSCC by activating the MAPK pathway. It also enhances anti-tumor activity by modulating the tumor immune microenvironment, promoting co-localization of p38 MAPK-activated CD4+ and CD8+ T cells.”

https://pubmed.ncbi.nlm.nih.gov/40475776/

“In conclusion, our study suggests that CBD inhibits tumor cell proliferation in HPV-positive HNSCC by activating MAPK pathway and exhibits anti-tumor activity by modulating the CD4+T and CD8+T cells in the tumor immune microenvironment. Therefore, CBD may potentially provide a supportive role in cancer therapy through immune-mediated mechanisms.”

“As such, specific cannabinoids may become an integral component of comprehensive cancer treatment regimens, offering new hope to patients with HPV-positive head and neck cancer.”

https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1528520/full

Cannabidiol and multi-modal exercise for chemotherapy-induced peripheral neuropathy in cancer survivors

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“Purpose: This study explored the effectiveness of cannabidiol (CBD) alone and in combination with multi-modal exercise (MME) to improve signs and symptoms of chemotherapy-induced peripheral neuropathy (CIPN), quality of life (QoL), and functional capacity in cancer survivors.

Methods: Cancer survivors (n = 27) with CIPN were enrolled in a 4-month interventional open-label study. Participants underwent two consecutive 2-month interventions: CBD (up to 300 mg/day) and CBD combined with MME. They were assessed using the painDETECT questionnaire for CIPN-related neuropathic pain and the Functional Assessment of Cancer Treatment/Gynecological Oncology-Neurotoxicity-13 (FACT-GOG-Ntx-13) questionnaire for CIPN neurotoxic symptoms (Ntx), perceived physical function (PPF) and overall QoL. Their functional status was examined through gait speed and timed up and go for mobility, the 9-hole peg test for manual dexterity, a hand-held hydraulic dynamometer for hand grip strength, and five repetitions sit-to-stand for dynamic balance, upper/lower extremity and overall strength.

Results: Positive effect sizes were measured by Cohen’s d or Cohen’s r with 95% confidence intervals (CI) from mean scores, and were d 0.62, CI 0.03-1.20 for Ntx; d 0.62, CI 0.09-1.26 for PPF; and r 0.401, CI 0.13-0.61 for hand grip strength after 2 months of CBD alone. After adding MME to CBD for another 2 months, the effect sizes were d 0.526, CI -0.15-1.19 for painDETECT; d 0.862, CI 0.67-1.55 for CIPN neurotoxic symptoms; d 1.03, CI 0.30-1.74 for perceived physical function; r 0.447, CI 0.15-0.67 for overall QoL; r 0.339, CI 0.03-0.59 for gait speed; and r 0.389, CI 0.08-0.63 for manual dexterity.

Conclusions: The study provides a proof of concept for the therapeutic effect of CBD alone and in combination with MME to improve symptoms’ burden, QoL and functional impairments related to CIPN in patients who are cured from cancer. Future randomized studies are needed to confirm the causal effects of CBD and exercise on CIPN, and to replicate our findings.”

https://pubmed.ncbi.nlm.nih.gov/40464985/

“This study provides a proof of concept supporting the use of CBD and multi-modal exercise (MME) to relieve CIPN in patients who are cured from cancer. Within the limitations of an observational study, our data suggest that 4 months of oral administration of CBD (up to 300 mg/day) in combination with 2 months of MME may provide clinically relevant improvements in CIPN-neurotoxic symptoms, neuropathic pain, QoL, and perceived physical function. CBD with or without MME may also positively affect functional capabilities such as muscle strength, gait speed, and manual dexterity, which are often impaired because of CIPN..”

https://link.springer.com/article/10.1007/s00520-025-09553-z

Targeting Gastrointestinal Cancers with Cannabidiol: Mechanisms, Challenges, and Therapeutic Implications

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“Cannabidiol (CBD), a non-psychoactive compound derived from cannabis, has gained significant attention for its potential therapeutic effects across various types of cancer.

This manuscript presents a systematic review of the current evidence on the application of CBD in gastrointestinal (GI) malignancies, with a focus on gastric and colorectal cancers.

The review aims to explore CBD’s mechanisms of action, including its effects on apoptosis, cell cycle regulation, angiogenesis, inflammation, and its potential to enhance the efficacy of conventional therapies. Furthermore, it examines the challenges involved in translating preclinical findings into clinical settings, such as issues related to bioavailability and regulatory hurdles.

The review also addresses future directions for the use of CBD in combination therapies and its potential to overcome resistance mechanisms in GI cancers. By analyzing the molecular pathways modulated by CBD, this manuscript seeks to offer a comprehensive understanding of its therapeutic potential, contributing to the future of GI cancer treatment.”

https://pubmed.ncbi.nlm.nih.gov/40461928/

https://link.springer.com/article/10.1007/s12032-025-02790-6

Complex forming properties of cannabinoid acids in a green solvent and bioassays focused on gastric disease caused by Helicobacter pylori infection

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“The main objective of the present study was to determine the protolytic and coordination properties of two bioactive cannabinoid acids (cannabidiolic acid and cannabigerolic acid) in ethyl alcohol-water mixture (50/50, v/v).

The complexation properties of these acids with copper(II) and zinc(II) ions were determined by potentiometric and ESI-MS methods. UV-Vis absorption spectra for the copper(II) systems confirmed the speciation models with one type of complex indicating coordination with completely deprotonated dinegative ligand molecule. The occurrence of precipitation at lower pH values limited the ability to determine complexes under these conditions.

The research also aimed to identify potential biological and medicinal applications of cannabinoid acids and their complexes with zinc(II). The ability of these compounds to influence the growth of human Hs68 skin fibroblasts and AGS gastric adenocarcinoma cells was investigated. Furthermore, these structures were tested against Helicobacter pylori strains, one of the factors promoting gastric cancer development.

At concentrations that were not-toxic to healthy cells (after dilution of the solutions, the composition of the ethanol/water mixture was approximately 1/99, v/v), the ligands exhibited bacterial inhibitory activity and cytotoxic properties against AGS cancer cells. Zinc(II) complexes, on the other hand, being biologically safe for all cells, had strong antibacterial properties, both inhibitory and bactericidal.”

https://pubmed.ncbi.nlm.nih.gov/40436988/

“Naturally occurring compounds known as plant cannabinoids or phytocannabinoids, responsible for the physiological effects of cannabis, have been used medicinally for thousands of years.”

https://www.nature.com/articles/s41598-025-03442-5

Proteomic Analysis of Invasive Breast Cancer Cells Treated with CBD Reveals Proteins Associated with the Reversal of Their Epithelial-Mesenchymal Transition Induced by IL-1β

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“Cannabidiol (CBD) has shown promise in treating cancers with an inflammatory microenvironment.

Although it has been demonstrated that IL-1β induces epithelial-mesenchymal transition (EMT) of MCF-7 cells and CBD reverts this process, in restoring the epithelial non-invasive phenotype, there is limited understanding of how this cannabinoid regulates these processes.

In this work, MCF-7 cells were induced to adopt an aggressive phenotype (6D cells), which was reversed by CBD.

Then, protein expression was analyzed by mass spectrometry to compare 6D vs. MCF-7 cells and 6D+CBD vs. 6D cells proteomes. Novel proteins associated with EMT and CBD signaling were identified. Twenty-four of them were oppositely regulated by IL-1β and CBD, suggesting new points of crosstalk between the IL-1β and CBD signaling pathways.

From the data, two protein networks were constructed: one related to EMT with 58 up-regulated proteins and another with 21 related to CBD signaling. The first one showed the proteins BRCA1, MSN, and CORO1A as the key axis that contributes to the establishment of a mesenchymal phenotype. In the CBD signaling, the key axis was formed by SUPT16H, SETD2, and H2BC12, which suggests epigenetic regulation by CBD in the restoration of an epithelial phenotype of breast cancer cells, providing new targets for anticancer therapy.”

https://pubmed.ncbi.nlm.nih.gov/40429863/

“All these results provide new important insights that could help to understand how CBD counteracts the effects of IL-1β and the restoration of the epithelial phenotype as a possible control of cancer progression.”

https://www.mdpi.com/1422-0067/26/10/4721

Nucleolar sequestration of cannabinoid type-2 receptors in triple-negative breast cancer cells

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“Multiple investigations have shown that the different types of cannabinoids, phytocannabinoids, synthetic cannabinoids, and endocannabinoids, possess antiproliferative and anticancer properties.

The cannabinoid type-2 receptor (CB2R) has been proposed as a central player in tumor progression and has been correlated with the aggressiveness of breast cancer. Using immunocytochemistry and confocal microscopy, in the present work, we studied the expression level and subcellular localization of CB2R in two human triple-negative breast cancer (TNBC) cell lines, corresponding to early (stage I, HCC-1395) and metastatic (MDA-MB-231) stages, and they were compared with a non-tumoral mammary epithelial cell line (MCF-10A).

We found that although CB2R was detected at the plasma membrane, it was mainly localized intracellularly, with ~40-fold higher expression in both TNBC cell lines than in MCF-10A (P < 0.0001). Notably, double staining with DAPI or with the nucleoli-specific fluorescent marker (3xnls-mTurquoise2) showed that most of the CB2R overexpressed in the nucleoli of cancer cells.

This finding is supported by the fact that CB2R expression was markedly lower in mitotic cells compared to interphase cells (P < 0.0001). Interestingly, exposure of cancer cells to the specific agonist HU-308 reversed the nucleolar sequestration of CB2R while increasing the presence of the receptor in the nucleoplasm and cytoplasm (P < 0.0001). In addition, we found that this agonist reduced both the cell migration (P < 0.05-0.0001) and proliferation (P < 0.001) of TNBC cells. It remains to determine the function and signaling ability of CB2R in the nucleolus.

Although our study only includes cell lines (tumoral and non-tumoral), we consider that this feature of nucleolar sequestration of CB2R could be a potential diagnostic marker for TNBC from the early stage.”

https://pubmed.ncbi.nlm.nih.gov/40359210/

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0323554

Cannabidiol-loaded-injectable depot formulation for the treatment of triple-negative breast cancer: design, development, in-vitro and in-ovo evaluation of its anticancer activity

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“Triple-negative breast cancer (TNBC) is an invasive and difficult-to-treat carcinoma that represents 15-20 % of breast malignancies and is frequently diagnosed in younger women. Chemotherapy is the mainstay treatment approach.

Cannabidiol (CBD), the main non-psychoactive cannabinoid, has shown a potential anticancer activity in TNBC, enhancing the effect of conventional antineoplastics.

This research aims to develop in situ forming implants (ISFIs) as a long-acting depot formulation of CBD with potential application in TNBC. This formulation is intended to be administered in the tumor site during neoadjuvant chemotherapeutic regimens, allowing a controlled CBD release. ISFIs were elaborated with 100 mg of polycaprolactone (PCL) and 2.5 mg (2.5-CB-ISFI), 5 mg (5-CB-ISFI) or 10 mg (10-CB-ISFI) of CBD dissolved in 400 µL of NMP. All the formulations exhibited a controlled drug release for around two months. 10-CB-ISFI formulation with the highest CBD content and the most suitable CBD release profile was selected for biological studies.

This formulation inhibited the proliferation and migration of MDA-MB-231 and 4T1 cells and exerted an antiangiogenic effect in ovo. Interestingly, the antiangiogenic activity of 10-CB-ISFI was higher compared with CBD in solution administered at the same concentration, showing vascular inhibition percentages of around 80 % and 60 %, respectively.

Finally, this formulation reduced the growth of MDA-MB-231-derived tumors developed in the chorioallantoic membrane (CAM) model. The single administration of 10-CB-ISFI exhibited a similar antitumor efficacy to the daily administration of CBD in solution (≈60 % tumor growth inhibition).

Therefore, the injectable depot formulation of CBD developed in this work showed a promising utility in TNBC treatment.”

https://pubmed.ncbi.nlm.nih.gov/40349999/

https://www.sciencedirect.com/science/article/pii/S0378517325005472?via%3Dihub

Cannabinol improves exemestane efficacy in estrogen receptor-positive breast cancer models: a comparative study with cannabidiol

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“Cannabinoids have been used as anti-emetic agents in cancer. However, multiple studies suggest that cannabinoids present important anti-tumor actions as well.

Estrogen receptor-positive (ER+) breast cancer is the most diagnosed breast cancer subtype, and despite the success of endocrine therapy, endocrine resistance development is a major challenge, demanding the discovery or implementation of alternative therapeutic approaches.

In line with this, and following our previous work, the benefits of combining the aromatase inhibitors (AIs) used in the clinic, anastrozole (Ana), letrozole (Let), and exemestane (Exe), with cannabinol (CBN) were evaluated. Experiments were performed in MCF-7aro cells and spheroids to assess activity against specific molecular targets and underlying mechanisms of action.

Among the three AIs studied, only the combination of CBN with Exe induced a significant beneficial impact on viability and growth of ER+ breast cancer cells and spheroids.

Our results demonstrated that this combination was more effective than Exe in preventing the expression of aromatase and in modulating ERα and androgen receptor (AR) activity.

In fact, the results revealed that CBN can prevent de novo synthesis of aromatase, surpass Exe’s weak estrogen-like effect, and avoid the unfavorable overexpression of AR. By comparing these two therapeutic strategies, as well as the previously studied combination of Exe plus cannabidiol (CBD), differential transcriptome profiles were detected, which may help to better understand the mechanism of action of cannabinoids and disclose their full potential in breast cancer treatment.

In conclusion, this study strengthens the hypothesis that cannabinoids are important anti-cancer agents with attractive co-adjuvant properties.”

https://pubmed.ncbi.nlm.nih.gov/40345424/

https://www.sciencedirect.com/science/article/pii/S0014299925004662?via%3Dihub