{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T18:24:04Z","timestamp":1788114244277,"version":"build-2803163510"},"reference-count":143,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T00:00:00Z","timestamp":1766361600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"State Key Laboratory of Neurology and Oncology Drug Development","award":["SKLSIM-20250182"],"award-info":[{"award-number":["SKLSIM-20250182"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Hinokiflavone (HF), a natural C-O-C-linked biflavonoid originally isolated from Chamaecyparis obtusa, is a promising multifunctional antitumor agent. Despite challenges posed by multidrug resistance and tumor heterogeneity, HF demonstrates notable therapeutic potential through a multifaceted pharmacological profile. HF exerts broad-spectrum anticancer effects by targeting multiple oncogenic pathways, including the MDM2-p53 axis, MAPK\/JNK\/NF-\u03baB signaling, ROS\/JNK-mediated apoptosis, and Bcl-2\/Bax-regulated mitochondrial pathways. These actions are further complemented by inhibition of cell proliferation through cell cycle arrest and suppression of metastasis via downregulation of matrix metalloproteinases and reversal of epithelial\u2013mesenchymal transition. Additionally, HF displays antioxidant, anti-inflammatory, and antimicrobial activities, enhancing treatment efficacy. However, its clinical translation remains limited by poor aqueous solubility, low oral bioavailability, and incomplete pharmacokinetic characterization. Recent advances in nanotechnology-based formulation strategies, such as polymeric micelles and metal\u2013organic frameworks, have enhanced HF\u2019s bioavailability and in vivo antitumor efficacy. This review comprehensively delineates HF\u2019s molecular mechanisms of anticancer action, evaluates its pharmacokinetics and bioformulation developments, and highlights challenges and prospects for clinical application. Integration of tumor microenvironment-responsive delivery systems with synergistic therapeutic strategies is essential to fully realize HF\u2019s therapeutic potential, positioning it as a valuable scaffold for novel anticancer drug development.<\/jats:p>","DOI":"10.3390\/cells15010017","type":"journal-article","created":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T11:43:31Z","timestamp":1766403811000},"page":"17","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Hinokiflavone as a Potential Antitumor Agent: From Pharmacology to Pharmaceutics"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-6183-3065","authenticated-orcid":false,"given":"Fengrui","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Zhongshan Hospital, Fudan University, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranyi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Zhongshan Hospital, Fudan University, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolei","family":"Zhou","sequence":"additional","affiliation":[{"name":"College of Biological Science and Engineering, Fuzhou University, Fuzhou 350108, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Zhongshan Hospital, Fudan University, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,22]]},"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. 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