{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T23:13:13Z","timestamp":1785366793818,"version":"3.55.0"},"reference-count":49,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,10,8]],"date-time":"2022-10-08T00:00:00Z","timestamp":1665187200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Imam Mohammed Ibn Saoud Islamic University (IMSIU)","award":["RP-21-09-87"],"award-info":[{"award-number":["RP-21-09-87"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Cannabinoids, the active components of cannabis exert palliative effects in cancer patients by preventing nausea, vomiting and pain as well as by stimulating appetite. Recent studies indicated that cannabinoids could be helpful in treating certain rare forms of cancer and other inflammatory diseases. The objective of this study was to investigate the cytotoxic effect of a cannabinoid mixture (CM) in oral cells. Thus, normal and cancer gingival cells were treated with different concentrations of CM to evaluate their proliferation by MTT assay, cytotoxicity by using LDH assay, colony formation with crystal violet and migration by the scratch method. In addition, apoptosis, autophagy, oxidative stress, antioxidant level, DNA damage and the mitochondrial membrane potential (\u0394\u03a8m) generated by proton pumps were measured by flow cytometry. Furthermore, deactivation of the key signaling pathways involved in cancer progression such as NF-\u03baB, ERK1\/2, p38, STAT1, STAT3, STAT5 was also evaluated by this technique. These outcomes indicate that CM, at a concentration higher than 0.1 \u00b5g\/mL, provokes high cytotoxicity in Ca9-22 oral cancer cells but not in GMSM-K gingival normal cells. Apoptosis, autophagy, antioxidant levels and mitochondrial stress as well as DNA damage in oral cells were increased following exposure to low concentration (1 \u00b5g\/mL). In addition, major signaling pathways that are involved such as MAPKase, STATs and NF-\u03baB pathways were inhibited by CM as well as cell migration. Our results suggest that cannabinoids could potentially have a beneficial effect on oral cancer therapy.<\/jats:p>","DOI":"10.3390\/cancers14194924","type":"journal-article","created":{"date-parts":[[2022,10,8]],"date-time":"2022-10-08T20:43:21Z","timestamp":1665261801000},"page":"4924","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Oxidative Stress and Autophagy Mediate Anti-Cancer Properties of Cannabis Derivatives in Human Oral Cancer Cells"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4744-5387","authenticated-orcid":false,"given":"Lionel","family":"Loubaki","sequence":"first","affiliation":[{"name":"H\u00e9ma-Qu\u00e9bec, 1070, Avenue des Sciences-de-la-Vie, Qu\u00e9bec, QC G1V 5C3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2205-8281","authenticated-orcid":false,"given":"Mahmoud","family":"Rouabhia","sequence":"additional","affiliation":[{"name":"Groupe de Recherche en \u00c9cologie Buccale, Facult\u00e9 de M\u00e9decine Dentaire, Universit\u00e9 Laval, Qu\u00e9bec, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed Al","family":"Zahrani","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 11623, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah Al","family":"Amri","sequence":"additional","affiliation":[{"name":"Biochemistry Department, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1643-0377","authenticated-orcid":false,"given":"Abdelhabib","family":"Semlali","sequence":"additional","affiliation":[{"name":"Groupe de Recherche en \u00c9cologie Buccale, Facult\u00e9 de M\u00e9decine Dentaire, Universit\u00e9 Laval, Qu\u00e9bec, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA-Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Zhang, S.Z., Xie, L., and Shang, Z.J. (2022). 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