Table 3 In vivo studies investigating the therapeutic potential of CBD in breast Cancer models
From: Cannabidiol as a novel therapeutic agent in breast cancer: evidence from literature
Study Title | Publication Year | Animal Model | Implanted Cells & Site | Carcinogen Use | Mode & Duration of Treatment | Sample Size | Outcomes Measured | Key Findings | References |
|---|---|---|---|---|---|---|---|---|---|
CBD Inhibits Tumor Development in Breast Cancer Models | 2023 | Mouse Xenograft Model | MCF-7 cells, subcutaneous implantation | No carcinogen used | Oral administration of CBD at varying doses for 6 weeks | 10 mice/group | Tumor growth inhibition, metastasis reduction, apoptosis induction | CBD significantly reduced tumor growth and metastasis | [19] |
CBD & THCV Overcome Doxorubicin Resistance in TNBC Xenografts | 2023 | Athymic Nude Mice Xenograft Model | MDA-MB-231 cells, subcutaneous implantation | No carcinogen used | CBD (10 mg/kg) + THCV (15 mg/kg) + DOX (5 mg/kg) for 6 weeks | 10 mice/group | Chemosensitivity enhancement, apoptosis induction, immune modulation | CBD/THCV increased DOX cytotoxicity, downregulated PD-L1 & TGF-β, overcoming resistance | 36 |
CB1 Inhibition Sensitizes TNBC to Ferroptosis via Fatty Acid Metabolism Regulation | 2022 | Mouse Xenograft Model | MDA-MB-231 cells, subcutaneous implantation | No carcinogen used | Rimonabant (CB1 antagonist) + Erastin/RSL3 for 4 weeks | 8 mice/group | Tumor growth reduction, lipid peroxidation, ROS production | CB1 inhibition increased ferroptosis sensitivity and reduced tumor growth | [41] |
Enhanced Therapeutic Efficacy of CBD via Nanoencapsulation & Combination with PPD | 2022 | Mouse Xenograft Model | 4T1 cells, subcutaneous implantation | No carcinogen used | Nanoencapsulated CBD + PPD for 5 weeks | 12 mice/group | Tumor inhibition, drug synergy, apoptosis induction | Nanoencapsulation improved CBD efficacy (82.2% tumor inhibition) and enhanced anticancer action with PPD | [42] |
Anticancer and Chemosensitization Effects of CBD in TNBC Models | 2022 | Ex Vivo Organotypic Model | MDA-MB-231, MDA-MB-468, MCF-10 A (organoid cultures) | No carcinogen used | CBD (1–10 µM) + DOX (0.39-25 µM) in TNBC 2D/3D models | Not applicable (ex vivo study) | Cell viability, migration, gene expression (GADD45A, Integrins), autophagy markers | CBD improved DOX sensitivity, suppressed TNBC invasion, inhibited autophagy via Beclin1 downregulation | [38] |
CBD Enhances Atezolizumab Efficacy via cGAS–STING Pathway Activation in TNBC Models | 2024 | Mouse Xenograft Model | MDA-MB-231 cells, subcutaneous implantation | No carcinogen used | CBD (dose not specified) + Atezolizumab for treatment duration (not specified) | Sample size not specified | PD-L1 expression, cGAS-STING activation, tumor apoptosis, immune response | CBD upregulated PD-L1 expression via cGAS-STING, enhancing atezolizumab efficacy in TNBC | [32] |
Antitumor activity of abnormal cannabidiol and its analog O-1602 in taxol-resistant preclinical models of breast cancer | 2019 | Zebrafish xenograft model | Paclitaxel-resistant MDA-MB-231 and MCF-7 breast cancer cells | No carcinogen used | Abnormal cannabidiol (Abn-CBD) and O-1602 at varying concentrations (e.g., 2 µM) | Not specified | Cell viability, apoptosis induction, tumor growth inhibition, gene expression analysis | Abn-CBD and O-1602 significantly inhibited proliferation of Taxol-resistant breast cancer cells, induced apoptosis, and reduced tumor growth in xenograft models. Enhanced Taxol’s efficacy via non-CB1/CB2 cannabinoid receptors, suggesting a novel mechanism of action | [29] |
Appraising the Entourage Effect: Antitumor Action of a Pure Cannabinoid Versus a Botanical Drug Preparation in Preclinical Models of Breast Cancer | 2018 | Mouse xenograft model | Breast cancer cell lines implanted subcutaneously | No carcinogen used | Pure cannabinoid and botanical drug preparation administered at varying doses | Not specified | Tumor growth inhibition, apoptosis induction, and gene expression analysis | Botanical drug preparation demonstrated enhanced antitumor activity compared to pure cannabinoid, supporting the entourage effect hypothesis | [28] |
Novel Role of Cannabinoid Receptor 2 in Inhibiting EGF/EGFR and IGF-I/IGF-IR Pathways in Breast Cancer | 2016 | Mouse xenograft model | ERα + and ERα- breast cancer cells implanted subcutaneously | No carcinogen used | JWH-015 (CNR2 agonist) administered at varying doses | Not specified | Tumor growth inhibition, reduced migration and invasion, suppression of EGFR and IGF-IR signaling pathways | CNR2 activation suppressed breast cancer growth through novel mechanisms by inhibiting EGF/EGFR and IGF-I/IGF-IR signaling axes | [27] |
Modulation of Breast Cancer Cell Viability by a Cannabinoid Receptor 2 Agonist, JWH-015, is Calcium Dependent | 2016 | Mouse xenograft model | Murine 4T1 and human MCF-7 breast cancer cells implanted subcutaneously | No carcinogen used | JWH-015 (CNR2 agonist) administered at varying doses | Not specified | Tumor growth inhibition, apoptosis induction, calcium-dependent signaling, MAPK/ERK pathway modulation | JWH-015 significantly reduced tumor burden and metastasis in vivo, induced apoptosis in vitro, and modulated calcium-dependent MAPK/ERK signaling pathways | [26] |
Bone Cell-Autonomous Contribution of Type 2 Cannabinoid Receptor to Breast Cancer-Induced Osteolysis | 2015 | Mouse xenograft model | Bone-tropic human and mouse breast cancer cells implanted in bone | No carcinogen used | CB2 agonists (e.g., HU308, JWH133) administered at varying doses | Not specified | Tumor-induced osteolysis, bone remodeling, osteoblast and osteoclast activity | CB2 activation reduced osteolysis and tumor burden, highlighting its role in regulating tumor-bone interactions and bone remodeling | [25] |
Cannabinoids Reduce ErbB2-Driven Breast Cancer Progression Through Akt Inhibition | 2010 | MMTV-neu mouse model | ErbB2-positive breast cancer cells implanted subcutaneously | No carcinogen used | Δ9-THC and JWH-133 (CB2 agonist) administered at varying doses | Not specified | Tumor growth inhibition, reduced metastasis, apoptosis induction, angiogenesis impairment | Cannabinoids significantly reduced tumor growth, metastasis, and angiogenesis. Their antitumor effects were mediated through Akt pathway inhibition, providing strong preclinical evidence for cannabinoid-based therapies in ErbB2-positive breast cancer | [24] |
Synthetic Cannabinoid Receptor Agonists Inhibit Tumor Growth and Metastasis of Breast Cancer | 2009 | Mouse xenograft model | MDA-MB-231 and MDA-MB-468 breast cancer cells implanted subcutaneously | No carcinogen used | JWH-133 (CB2 agonist) and WIN-55,212-2 (CB1/CB2 agonist) administered at varying doses | Not specified | Tumor growth inhibition, reduced metastasis, apoptosis induction, COX-2/prostaglandin E2 pathway modulation | JWH-133 and WIN-55,212-2 significantly reduced tumor growth (40-50%) and lung metastasis (65-80%) in vivo. Effects were mediated through CB1/CB2 receptors and involved COX-2/prostaglandin E2 signaling pathways | [23] |