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Preclinical data indicate that THC has a strong anti\u2010inflammatory, antioxidant, and anticancer profile, and as such, it is a better alternative to curcumin in treatment. Mechanistically, THC regulates important transcriptional factors that are involved in tumorigenesis, specifically nuclear factor\u2010kappa B (NF\u2010kB) and activator protein\u20101 (AP\u20101). Uncontrolled proliferation, inflammation, and resistance to apoptosis have been linked to aberrant activation of these pathways. Inhibition of NF\u2010kB and AP\u20101 induced by THC suppresses cancer cell survival signaling and triggers apoptotic cell death. Simultaneously, THC inhibits the action of matrix metalloproteinases (MMPs), which are involved in the degradation of extra cells and metastatic spread, and promote tumor invasion and metastasis. Experimental research has also shown the effectiveness of THC in various cancers such as breast cancer, prostate cancer, colon cancer, and skin cancer. It is important to note that THC increases the therapeutic index of traditional chemotherapeutics, where they show synergistic interactions and counteract drug resistance mechanisms, which is a key obstacle in clinical oncology. THC has better physiological stability and bioavailability compared to its parent molecule, a characteristic that alleviates one of the greatest translational limitations of curcumin. This review highlights the molecular processes underlying the anticancer action of THC, its possible use as a single agent and as an adjuvant to already established chemotherapeutic protocols, and the translational issues that need to be overcome to achieve clinical acceptance. Together, the existing evidence supports THC as an attractive future cancer therapeutic with the potential to improve treatment outcomes and overcome drug resistance.<\/jats:p>","DOI":"10.1002\/fsn3.71125","type":"journal-article","created":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T05:30:07Z","timestamp":1761802207000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Elucidating the Anticancer Mechanisms of Tetrahydroxycurcumin: A Comprehensive Review of Preclinical Studies"],"prefix":"10.1002","volume":"13","author":[{"given":"Muhammad","family":"Shahbaz","sequence":"first","affiliation":[{"name":"Department of Food Science and Technology Muhammad Nawaz Shareef University of Agriculture  Multan Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ushna","family":"Momal","sequence":"additional","affiliation":[{"name":"Department of Food Science and Technology Muhammad Nawaz Shareef University of Agriculture  Multan Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hagar M.","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Analysis, College of Medical &amp; Health Sciences Liwa University  Abu Dhabi UAE"},{"name":"Department of Applied Medical Chemistry Medical Research Institute, Alexandria University  Alexandria Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asfa","family":"Perween","sequence":"additional","affiliation":[{"name":"Department of Human Nutrition and Dietetics Muhammad Nawaz Shareef University of Agriculture  Multan Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hammad","family":"Naeem","sequence":"additional","affiliation":[{"name":"Department of Food Science and Technology Muhammad Nawaz Shareef University of Agriculture  Multan Pakistan"},{"name":"Food Technology section, Post Harvest Research Centre Ayub Agricultural Research Institute  Faisalabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Imran","sequence":"additional","affiliation":[{"name":"Department of Food Science and Technology University of Narowal  Narowal Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6508-1962","authenticated-orcid":false,"given":"Muzzamal","family":"Hussain","sequence":"additional","affiliation":[{"name":"Department of Food Sciences Government College University Faisalabad  Faisalabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gamal A.","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Department of Natural Products and Alternative Medicine, Faculty of Pharmacy King Abdulaziz University  Jeddah Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6858-7560","authenticated-orcid":false,"given":"Sabrin R. 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