{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:30:26Z","timestamp":1787027426842,"version":"build-2736575974"},"reference-count":103,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Bergapten is a plant-derived linear furanocoumarin widely distributed in Rutaceae and Apiaceae species and increasingly recognized for its multifunctional anticancer potential. This review critically synthesizes current evidence on bergapten\u2019s biosynthesis, physicochemical and pharmacokinetic properties, anti-inflammatory and antioxidant pharmacodynamics, and mechanistic antitumor activity, highlighting its translational relevance within pharmaceutical development. Preclinical studies across diverse malignancies demonstrate pleiotropic anticancer effects. Mechanistically, bergapten activates mitochondrial apoptosis via Bax\/Bcl-2 modulation and caspase cascades, induces cell cycle arrest through p53\u2013p21 signaling, and suppresses PI3K\/Akt\/mTOR and NF-\u03baB pathways. Additional effects include PTEN-mediated autophagy induction, interference with metabolic reprogramming, reversal of multidrug resistance through ABC transporter modulation, and context-dependent photoactivated cytotoxicity. Beyond direct tumor cell targeting, bergapten attenuates pro-inflammatory mediators and regulates redox homeostasis through downregulation of NOX4-derived ROS and activation of Nrf2-driven antioxidant defenses, addressing the redox\u2013inflammatory axis implicated in carcinogenesis. Despite promising mechanistic depth, clinical translation is limited by incomplete human pharmacokinetic data and poor aqueous solubility. Nanotechnology-enabled delivery systems and structural derivatives offer strategies to enhance bioavailability and therapeutic index. Overall, bergapten emerges as a systems-level phytochemical candidate warranting further translational investigation in oncology.<\/jats:p>","DOI":"10.3390\/pharmaceutics18081007","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T13:12:56Z","timestamp":1786713176000},"page":"1007","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bergapten as a Multifunctional Phytochemical in Cancer Therapy: Mechanistic Insights, Pharmacokinetics, and Possible Nanotechnology-Enabled Formulation Strategies"],"prefix":"10.3390","volume":"18","author":[{"given":"Vict\u00f3ria Dogani","family":"Rodrigues","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Pharmacology, School of Medicine, Faculdade de Medicina de Mar\u00edlia (FAMEMA), Mar\u00edlia 17519-030, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4979-115X","authenticated-orcid":false,"given":"Maria Ang\u00e9lica","family":"Miglino","sequence":"additional","affiliation":[{"name":"Graduate Program in Structural and Functional Interactions in Rehabilitation, School of Medicine, Universidade de Mar\u00edlia (UNIMAR), Mar\u00edlia 17525-902, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cla\u00fadia Rucco Penteado","family":"Detregiachi","sequence":"additional","affiliation":[{"name":"Graduate Program in Structural and Functional Interactions in Rehabilitation, School of Medicine, Universidade de Mar\u00edlia (UNIMAR), Mar\u00edlia 17525-902, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5035-876X","authenticated-orcid":false,"given":"Sandra Maria","family":"Barbalho","sequence":"additional","affiliation":[{"name":"Graduate Program in Structural and Functional Interactions in Rehabilitation, School of Medicine, Universidade de Mar\u00edlia (UNIMAR), Mar\u00edlia 17525-902, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas Fornari","family":"Laurindo","sequence":"additional","affiliation":[{"name":"Division of Cellular Growth, Hemodynamics, and Homeostasis Disorders, Graduate Program in Medical Sciences, Faculdade de Medicina, Universidade de S\u00e3o Paulo (USP), S\u00e3o Paulo 01246-903, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s43556-024-00239-2","article-title":"Molecular mechanisms and therapeutic strategies in overcoming chemotherapy resistance in cancer","volume":"6","author":"Gu","year":"2025","journal-title":"Mol. 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