{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T11:04:56Z","timestamp":1766487896157,"version":"3.48.0"},"reference-count":79,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T00:00:00Z","timestamp":1766448000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"AMITD"},{"name":"DSTI Presidential Cannabis and Hemp Development Masterplan"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Breast cancer remains a leading cause of cancer-related morbidity and mortality globally, highlighting the urgent need for novel therapeutic strategies. This study investigates the molecular mechanisms underlying the anti-proliferative potential of Cannabis sativa dichloromethane extract (C. sativa DCM) on oxidative stress, apoptosis, and invasion in human breast cancer cells. Key biomarkers, such as antioxidant enzymes (Superoxide Dismutase (SOD) and Glutathione (GSH)), the transcription factor Nrf2, apoptotic proteins (p53, caspase-8 and 9), metalloproteinase (MMP-1 and MMP-9), and Transforming Growth Factor Beta (TGF-\u03b2) were examined. Cytotoxicity was assessed using an MTT assay in the MDA-MB-231 and MCF-7 breast cancer cell lines, with comparisons to normal skin fibroblasts (HS27). Oxidative stress biomarkers were quantified using enzymatic assays and ELISA kits, while apoptotic and anti-metastatic factors were determined by Western blotting. Results demonstrated that C. sativa DCM extract induced significant cell death in a concentration-dependent manner, with IC50 values of 75.46 \u00b1 0.132 \u03bcg\/mL for MDA-MB-231 and 78.68 \u00b1 0.50 \u03bcg\/mL for MCF-7 cells. The extract decreased SOD and GSH levels while increasing p53 and caspase activity, confirming apoptosis activation. Additionally, C. sativa DCM inhibited migration and invasion by downregulating MMP-1, MMP-9, and TGF-\u03b2. The anti-proliferative potential of C. sativa DCM in breast cancer cells is mediated through a continuous biological pathway involving oxidative stress modulation, apoptotic signaling, and anti-invasive effects. Phytochemical analysis revealed terpenoids and steroids, including compounds like cannabidiol and tetrahydrocannabinol acid. These findings suggest that C. sativa DCM extract holds potential as an anti-breast cancer therapeutic and warrants further preclinical and clinical investigations.<\/jats:p>","DOI":"10.3390\/ijms27010152","type":"journal-article","created":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T10:57:18Z","timestamp":1766487438000},"page":"152","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Potential Anticancer Effect of Cannabis sativa L. Dichloromethane Extract Through Oxidative Stress-Related Pathways and the Inhibition of the Migration and Invasiveness of Human Breast Cancer Cells (MDA-MB-231 and MCF-7)"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9399-6561","authenticated-orcid":false,"given":"Corinne Ra\u00efssa","family":"Ngnameko","sequence":"first","affiliation":[{"name":"African Medicines Innovations and Technologies Development, Department of Pharmacology, Faculty of Health Sciences, University of the Free State, P.O. Box 339, Bloemfontein 9300, South Africa"},{"name":"Pharmacology and Drug Discovery Laboratory, Institute of Medical Research and Medicinal Plants Studies, Yaound\u00e9 P.O. Box 13033, Cameroon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8897-1866","authenticated-orcid":false,"given":"Jacqueline Njikam","family":"Manjia","sequence":"additional","affiliation":[{"name":"African Medicines Innovations and Technologies Development, Department of Pharmacology, Faculty of Health Sciences, University of the Free State, P.O. Box 339, Bloemfontein 9300, South Africa"},{"name":"Laboratory of Pharmacology and Toxicology, Department of Biochemistry, Faculty of Science, University of Yaound\u00e9 I, Yaound\u00e9 P.O. Box 812, Cameroon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2921-8882","authenticated-orcid":false,"given":"Motlalepula Gilbert","family":"Matsabisa","sequence":"additional","affiliation":[{"name":"African Medicines Innovations and Technologies Development, Department of Pharmacology, Faculty of Health Sciences, University of the Free State, P.O. Box 339, Bloemfontein 9300, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,23]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1016\/j.biopha.2017.05.043","article-title":"Effect of Au-Dextran NPs as Anti-Tumor Agent against EAC and Solid Tumor in Mice by Biochemical Evaluations and Histopathological Investigations","volume":"91","author":"Medhat","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_3","first-page":"2920","article-title":"Breast Cancer: Molecular Mechanisms of Underlying Resistance and Therapeutic Approaches","volume":"12","author":"Tufail","year":"2022","journal-title":"Am. J. 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