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Evidence suggests that THF exerts anticancer activity by distinct mechanisms of action. This study explores the anticancer potential of THF in human lung (A549) and skin (A431) cancer cells by employing different antiproliferative assays. 3\u2010(4,5\u2010Dimethylthiazol\u20102\u2010yl)\u22122,5\u2010diphenyltetrazolium bromide, neutral red uptake, sulphorhodamine B, and cell motility assays were used to confirm the anticancer potential of THF. Cell target\u2010based and quantitative reverse transcription polymerase chain reaction (qRT\u2010PCR) assays were used to explore the effect of THF on the initiation, promotion and progression phase biomarkers of carcinogenesis. THF suppresses the activity of lipoxygenase\u20105 up to ~40% in both A549 and A431 cells and up to ~50% hyaluronidase activity in A549 cells. qRT\u2010PCR assay reveals that THF inhibits the activity of phosphatidyl inositol\u20103 kinase\/protein kinase B\/mammalian target of rapamycin in both cell lines, which is responsible for the initiation of cancer. It also arrests the G2\/M phase of the cell cycle in A431 cells and increases the sub\u2010diploid population in both A549 and A431 cell lines which leads to cell death. Annexin V\u2010FITC assay confirmed that THF induces apoptosis and necrosis in A431 and A549 cell lines. Further investigation revealed that THF not only enhances reactive oxygen species production but also modulates mitochondrial membrane potential in both cell lines. It significantly inhibits S\u2010180 tumour formation at 5 and 10\u2009mg\/kg bw, <jats:italic>i.p.<\/jats:italic> dose. An acute skin toxicity study on mice showed that erythema and edema scores are within the acceptable range, besides acceptable drug\u2010likeness properties and non\u2010toxic effects on human erythrocytes. Conclusively, THF showed potent anticancer activity on skin and lung carcinoma cell lines, suppressed the level of the biomarkers and inhibited tumour growth in mice.<\/jats:p>","DOI":"10.1002\/jbt.23838","type":"journal-article","created":{"date-parts":[[2024,9,7]],"date-time":"2024-09-07T11:10:02Z","timestamp":1725707402000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["THF induces apoptosis by downregulating initiation, promotion, and progression phase biomarkers in skin and lung carcinoma"],"prefix":"10.1002","volume":"38","author":[{"given":"Waseem","family":"Raza","sequence":"first","affiliation":[{"name":"Bioprospection and Product Development Division CSIR\u2010Central Institute of Medicinal and Aromatic Plants Lucknow India"},{"name":"Jawaharlal Nehru University New Delhi India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1014-1486","authenticated-orcid":false,"given":"Abha","family":"Meena","sequence":"additional","affiliation":[{"name":"Bioprospection and Product Development Division CSIR\u2010Central Institute of Medicinal and Aromatic Plants Lucknow India"},{"name":"Academy of Scientific and Innovative Research (AcSIR) Ghaziabad India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6568-8107","authenticated-orcid":false,"given":"Suaib","family":"Luqman","sequence":"additional","affiliation":[{"name":"Bioprospection and Product Development Division CSIR\u2010Central Institute of Medicinal and Aromatic Plants Lucknow India"},{"name":"Academy of Scientific and Innovative Research (AcSIR) Ghaziabad India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,9,7]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2005.07.008"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2005.05.011"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biotechadv.2018.11.005"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/15353702211062510"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-8741(97)00065-2"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.7874"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.111808"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2008.02.025"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2016.10.111"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.110.069591"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jff.2015.03.051"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12935-015-0168-2"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.3892\/or.2016.5224"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.14348\/molcells.2015.2229"},{"key":"e_1_2_12_16_1","first-page":"667","volume":"17","author":"Lei D.","year":"2018","journal-title":"Mol. 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