{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T17:27:45Z","timestamp":1780939665370,"version":"3.54.1"},"reference-count":29,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T00:00:00Z","timestamp":1760659200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Cancer is characterized by uncontrolled cell proliferation and the evasion of programmed cell death. The dysregulation of the cell cycle is a fundamental hallmark of nearly all human cancers, making its core machinery an attractive target for therapeutic intervention. Concurrently, the ability of cancer cells to resist apoptotic signals is a primary mechanism of tumorigenesis and therapy resistance. This has spurred the search for agents that can simultaneously reinstate cell cycle control and trigger robust cell death pathways. Natural products, particularly polyphenols, have emerged as a promising source. Pyrogallol (1,2,3\u2010trihydroxybenzene), a simple phenolic compound found in numerous plants, has demonstrated potent anticancer activities across a wide range of malignancies. This review synthesizes the current understanding of pyrogallol's mechanism of action, rooted in its pro\u2010oxidant nature. Pyrogallol autoxidation generates a massive burst of intracellular Reactive Oxygen Species (ROS) and causes a concomitant depletion of Glutathione (GSH), creating severe oxidative stress. This oxidative assault is particularly effective against cancer cells, which often have a compromised redox balance, rendering them more vulnerable than their normal counterparts. This ROS\/GSH imbalance acts as a master signal to initiate a multifaceted attack on cancer cells by comprehensively rewiring cellular signaling, leading to the inhibition of critical pro\u2010survival pathways (e.g., PI3K\/Akt) and the activation of stress\u2010responsive kinase pathways (e.g., JNK, p38). These signaling alterations converge to induce robust cell cycle arrest, primarily at the G2\/M transition, and trigger the intrinsic mitochondrial pathway of apoptosis, marked by mitochondrial membrane depolarization, modulation of Bcl\u20102 family proteins, and caspase activation. This review provides a cohesive model of pyrogallol's action, highlighting its potential as a lead compound for developing novel oxidative therapies that exploit the inherent redox vulnerabilities of cancer cells.<\/jats:p>","DOI":"10.1002\/jat.4962","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T14:04:34Z","timestamp":1760709874000},"page":"434-442","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Oxidative Assault: How Pyrogallol's Pro\u2010Oxidant Chemistry Drives Cell Cycle Arrest and Apoptosis in Cancer"],"prefix":"10.1002","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4341-5188","authenticated-orcid":false,"given":"Woo\u00a0Hyun","family":"Park","sequence":"first","affiliation":[{"name":"Department of Physiology Medical School, Jeonbuk National University  Jeonju Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,17]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20163985"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24076452"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2019.101207"},{"issue":"6","key":"e_1_2_14_5_1","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1016\/j.cmet.2025.04.017","article-title":"Metabolic Switches in Cell Death Regulation","volume":"37","author":"Galluzzi L.","year":"2025","journal-title":"Cell Metabolism"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmr.2024.100030"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-024-01429-4"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2017.6185"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2008.06.014"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.20263"},{"issue":"5","key":"e_1_2_14_11_1","first-page":"1099","article-title":"Caspase Inhibitor Decreases Apoptosis in Pyrogallol\u2010Treated Lung Cancer Calu\u20106 Cells via the Prevention of GSH Depletion","volume":"33","author":"Han Y. H.","year":"2008","journal-title":"International Journal of Oncology"},{"issue":"6","key":"e_1_2_14_12_1","first-page":"721","article-title":"Pyrogallol as a Glutathione Depletor Induces Apoptosis in HeLa Cells","volume":"21","author":"Han Y. H.","year":"2008","journal-title":"International Journal of Molecular Medicine"},{"issue":"5","key":"e_1_2_14_13_1","first-page":"717","article-title":"JNK and p38 Inhibitors Increase and Decrease Apoptosis, Respectively, in Pyrogallol\u2010Treated Calf Pulmonary Arterial Endothelial Cells","volume":"24","author":"Han Y. H.","year":"2009","journal-title":"International Journal of Molecular Medicine"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2009.11.032"},{"issue":"1","key":"e_1_2_14_15_1","first-page":"187","article-title":"Identification of Pyrogallol as an Antiproliferative Compound Present in Extracts From the Medicinal Plant Emblica Officinalis: Effects on In\u00a0Vitro Cell Growth of Human Tumor Cell Lines","volume":"21","author":"Khan M. T.","year":"2002","journal-title":"International Journal of Oncology"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/mc.20369"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.22942"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-025-00842-3"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-021-00404-3"},{"key":"e_1_2_14_20_1","unstructured":"National Center for Biotechnology Information \u201cPubChem Compound Summary for CID 1057 Pyrogallol\u201d. (2025). Retrieved July 11 2025 fromhttps:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/Pyrogallol."},{"key":"e_1_2_14_21_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2016.3543"},{"key":"e_1_2_14_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2007.03.018"},{"key":"e_1_2_14_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2021.03.010"},{"key":"e_1_2_14_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm061400l"},{"key":"e_1_2_14_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12032-025-02835-w"},{"key":"e_1_2_14_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-025-00841-8"},{"key":"e_1_2_14_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-0102(02)00196-7"},{"key":"e_1_2_14_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2009.01.016"},{"key":"e_1_2_14_29_1","doi-asserted-by":"publisher","DOI":"10.1039\/D5FO02116B"},{"key":"e_1_2_14_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/tox.24099"}],"container-title":["Journal of Applied Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jat.4962","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T04:10:39Z","timestamp":1768191039000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/jat.4962"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,17]]},"references-count":29,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1002\/jat.4962"],"URL":"https:\/\/doi.org\/10.1002\/jat.4962","archive":["Portico"],"relation":{},"ISSN":["0260-437X","1099-1263"],"issn-type":[{"value":"0260-437X","type":"print"},{"value":"1099-1263","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,17]]},"assertion":[{"value":"2025-07-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}