“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

“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

“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

“Background: Breast cancer is one of the most prevalent cancers worldwide, posing significant challenges due to its heterogeneity and the emergence of drug resistance. Cannabidiol (CBD), a non-psychoactive compound derived from Cannabis sativa, has recently gained attention for its potential therapeutic effects in breast cancer.

Objective: This review aims to evaluate the antitumor effects of CBD in breast cancer treatment by synthesizing preclinical and clinical evidence, elucidating its mechanisms of action, and exploring its translational potential.

Methods: A systematic review was conducted following PRISMA guidelines. A comprehensive search was performed across PubMed, Google Scholar, Web of Science, and Scopus databases, using keywords such as “Cannabidiol,” “CBD,” “Breast Cancer,” “Therapeutic Agent,” and “Antitumor Effects.” A total of 1,191 articles were initially identified. After duplicate removal and eligibility screening, 34 studies published between 1998 and 2025 were selected, including in vitro, in vivo, and clinical investigations. Studies were assessed based on PRISMA recommendations, considering inclusion criteria such as CBD’s impact on apoptosis, cell proliferation, tumor progression, and molecular mechanisms.

Results: CBD demonstrated significant anticancer effects, including induction of apoptosis, inhibition of cell proliferation, suppression of metastasis, and modulation of the tumor microenvironment. Mechanistically, CBD modulates key pathways such as PI3K/Akt, mTOR, and PPARγ and interacts with CB1, CB2, and non-cannabinoid receptors. Preclinical studies showed CBD’s efficacy, particularly in triple-negative breast cancer (TNBC), while limited clinical trials highlighted its potential as an adjunct to conventional therapies.

Conclusion: CBD offers a promising therapeutic approach for breast cancer, especially for aggressive subtypes like TNBC. However, challenges such as variability in study design, lack of standardized protocols, and limited clinical validation hinder its clinical application. Future research should focus on conducting robust clinical trials, identifying predictive biomarkers, and optimizing combinatorial therapies to integrate CBD into personalized cancer treatment strategies.”

https://pubmed.ncbi.nlm.nih.gov/40275168/

“CBD holds significant promise as a complementary or standalone therapeutic agent in breast cancer treatment, particularly in TNBC, where conventional options are limited. However, clinical validation through well-designed trials, biomarker identification, and safety profiling remains imperative before widespread clinical adoption. Future studies should focus on optimizing combinatorial therapies, investigating long-term effects, and refining pharmacological formulations to bridge the gap between preclinical findings and clinical application. By addressing these challenges, CBD could potentially redefine breast cancer management strategies, offering a safer, more effective, and targeted approach to treatment.”

https://bmccancer.biomedcentral.com/articles/10.1186/s12885-025-14175-z

“Background: High dose chemotherapy is one of the therapeutic strategies for breast cancer and doxorubicin (DOX) as a chemotherapy agent is widely used. DOX indication is limited due to its dose-depended cardiotoxicity. Recently, cannabidiol (CBD) shows antitumoral and cardioprotective effects, so we hypothesized that CBD administration with high-dose DOX chemotherapy can improve anticancer activity and reduce cardiotoxic side effects.

Method: Mice breast cancer model established by injecting 4T1 cell lines. One group was not injected by 4T1 cells as a not cancerous group and received normal saline (NS, 0.1 mL). In cancerous groups, first group was considered as cancerous control and received NS (0.1 mL); the second group received CBD (5 mg/kg, IP) on Days 1,7, and 14; in the third group DOX (5 mg/kg, IV) as CBD schedule was administrated; the fourth group treated with CBD 1 day before DOX injection as pretreatment, and the last group was treated with CBD and DOX at same time with previous doses and schedules. On Day 21, all mice were sacrificed, heart and lungs tissues were obtained and histological sections were isolated. SOD2, iNOS, MMP2, MMP9 were evaluated through western blot and TUNEL test preformed for breast tumor.

Results: Tumor size and weight significantly decreased in DOX, pretreatment CBD + DOX and CBD + DOX groups. Administration of CBD with DOX could not prevent weight loss. TUNEL test demonstrated the highest tumor cell apoptosis in pretreatment CBD + DOX and CBD + DOX. In lungs belonged to CBD + DOX, there was not any sign of metastasis. Cardiac histopathological examination of pretreatment CBD + DOX and CBD + DOX did not show any sign of congestion or inflammation. In CBD + DOX SOD2 increased, also iNOS, MMP2, and MMP9 decreased compared to DOX.

Conclusions: This study demonstrated that simultaneous administration of CBD and DOX can increase antitumoral effect and reduce DOX cardiotoxicity. Nevertheless, CBD can induce cardiotoxicity as administrated alone.”

https://pubmed.ncbi.nlm.nih.gov/39503169/

“This study demonstrated the potent efficacy of cannabidiol in mouse breast cancer model with high-dose chemotherapy on the antitumor, anti-metastasis and cardioprotective roles against doxorubicin. Simultaneous administration of cannabidiol with high-dose doxorubicin not only improved the antitumor and anti-metastasis efficacy, but also could reduce cardiotoxicity by decreasing MMP2 and MMP9 and improving cardiac function by decreasing iNOS. Furthermore, cannabidiol could improve antioxidant system by increasing SOD2. Eventually, these findings demonstrated cannabidiol as a potential effective agent in coadministration with doxorubicin at the same time in improving anticancer effects and reducing cardiotoxicity.”

https://onlinelibrary.wiley.com/doi/10.1002/cam4.70395