{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T17:25:21Z","timestamp":1792603521381,"version":"4.5.0"},"reference-count":195,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,9,28]],"date-time":"2025-09-28T00:00:00Z","timestamp":1759017600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"IMU University","award":["IMU 558-2022"],"award-info":[{"award-number":["IMU 558-2022"]}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Nutrients"],"abstract":"<jats:p>Shikonin, a dietary naphthoquinone phytochemical from the roots of Lithospermum erythrorhizon, has gained attention for its anticancer potential. Preclinical studies show that shikonin regulates multiple programmed cell death pathways, including apoptosis, necroptosis, ferroptosis, and pyroptosis, through mechanisms involving reactive oxygen species (ROS) accumulation, mitochondrial dysfunction, and kinase-mediated signalling. Beyond cytotoxicity, shikonin suppresses metastasis by blocking epithelial\u2013mesenchymal transition (EMT) and downregulating matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). It also disrupts tumour metabolism by targeting pyruvate kinase isoform M2 (PKM2) and modulating the Warburg effect. Evidence further indicates that shikonin can enhance the efficacy of chemotherapy, targeted therapy, immunotherapy, and radiotherapy, thereby contributing to the reversal of therapeutic resistance. To address limitations related to solubility and bioavailability, novel formulations such as nanoparticles, liposomes, and derivatives like \u03b2,\u03b2-dimethylacrylshikonin have been developed, showing improved pharmacological profiles and reduced toxicity in experimental models. Overall, the current literature identifies shikonin as a promising dietary phytochemical with diverse anticancer activities, therapeutic synergy, and formulation advances, while highlighting the need for clinical studies to establish its translational potential.<\/jats:p>","DOI":"10.3390\/nu17193085","type":"journal-article","created":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T11:40:52Z","timestamp":1759146052000},"page":"3085","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Shikonin as a Dietary Phytochemical with Multi-Target Anti-Cancer Activities: From Molecular Mechanisms to Translational Applications"],"prefix":"10.3390","volume":"17","author":[{"given":"Chun-Yik","family":"Lew","sequence":"first","affiliation":[{"name":"School of Health Science, IMU University, No. 126, Jalan Jalil Perkasa 19, Bukit Jalil, Kuala Lumpur 57000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Teng","family":"Tang","sequence":"additional","affiliation":[{"name":"School of Health Science, IMU University, No. 126, Jalan Jalil Perkasa 19, Bukit Jalil, Kuala Lumpur 57000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda Yee-Jing","family":"Lee","sequence":"additional","affiliation":[{"name":"School of Health Science, IMU University, No. 126, Jalan Jalil Perkasa 19, Bukit Jalil, Kuala Lumpur 57000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Jian","family":"Chin","sequence":"additional","affiliation":[{"name":"School of Health Science, IMU University, No. 126, Jalan Jalil Perkasa 19, Bukit Jalil, Kuala Lumpur 57000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan-Ling","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Chang Gung Memorial Hospital at Chiayi, No. 8, West Section of Jiapu Road, Puzi City 613016, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0578-7116","authenticated-orcid":false,"given":"Ching-Hsein","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Biopharmaceuticals, College of Life Sciences, A25-303 Room, Life Sciences Hall, National Chiayi University, No. 300, Syuefu Road, Chiayi City 600355, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soi-Moi","family":"Chye","sequence":"additional","affiliation":[{"name":"School of Health Science, Division of Applied Biomedical Science and Biotechnology, IMU University, No. 126, Jalan Jalil Perkasa 19, Bukit Jalil, Kuala Lumpur 57000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,28]]},"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":"20503121211034366","DOI":"10.1177\/20503121211034366","article-title":"New approaches and procedures for cancer treatment: Current perspectives","volume":"9","author":"Debela","year":"2021","journal-title":"SAGE Open Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1186\/s12964-023-01302-1","article-title":"Unveiling the mechanisms and challenges of cancer drug resistance","volume":"22","author":"Khan","year":"2024","journal-title":"Cell Commun. 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