{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T21:32:16Z","timestamp":1768512736902,"version":"3.49.0"},"reference-count":31,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,12,30]],"date-time":"2020-12-30T00:00:00Z","timestamp":1609286400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Ciencia y Tecnolog\u00eda","doi-asserted-by":"publisher","award":["Catedras\u2010CONACYT no. 1059"],"award-info":[{"award-number":["Catedras\u2010CONACYT no. 1059"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Ciencia y Tecnolog\u00eda","doi-asserted-by":"publisher","award":["SALUD\u20112014\u20111\u2011233868: SALUD\u20102016\u20101\u2010272633: SEP\u2010CONACYT M\u00e9xico 243233"],"award-info":[{"award-number":["SALUD\u20112014\u20111\u2011233868: SALUD\u20102016\u20101\u2010272633: SEP\u2010CONACYT M\u00e9xico 243233"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Biochemistry &amp;amp; Function"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:sec><jats:label\/><jats:p>Low levels of oxygen (hypoxia) have been reported in solid tumours. This hypoxic microenvironment modulates the expression of genes linked to a more aggressive disease. However, it is unclear if the expression of drug\u2010metabolizing enzymes as cytochromes P450 (CYPs) is affected by hypoxia in cancer. We aimed to define which cytochromes are affected by hypoxia using a liver cancer model in vitro. For this purpose, we assessed whole\u2010genome expression microarrays of HepG2 liver cancer cell line from free repository databases, looking for gene expression hypoxia\u2010associated profiles and selected those cytochromes with significant differences. Then, we corroborated their mRNA expression and protein levels by RT\u2010qPCR and western blot, respectively, as well as immunofluorescence. Based on microarray analysis, we found that the expression of CYP2S1 and CYP24A1 were up\u2010regulated with at least twice fold change compared with normoxia. The levels of mRNA and protein of CYP2S1 and CYP24A1 were increased significantly in hypoxic conditions (<jats:italic>P<\/jats:italic>\u2009&lt;\u2009.05), and this tendency was also observed by immunofluorescence assays. Our data show that the expression of cytochromes CYP2S1 and CYP24A1 are induced in hypoxia, being the first time that CYP24A1 expression is associated with tumour hypoxia; which might have consequences in cancer progression and drug resistance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance of the study<\/jats:title><jats:p>Hypoxia is among the most important factors for cellular adaptation to stress. Especially in cancer, a major public health issue, hypoxia plays a substantial role in angiogenesis, metastasis and resistance to therapy. Tumoral hypoxia has been described at least in the brain, breast, cervical, liver, renal, lung, pancreatic and renal cancer. However, the understanding of how hypoxia drives cancer progression is still a major challenge. One emerging question is the role of hypoxia over the expression of drug\u2010metabolizing enzymes, with a significant impact on drug treatment. In this context, our paper focus on the effect of hypoxia on CYPs, which is an essential group of drug\u2010metabolizing enzymes. We show that hypoxia induces the expression of two members of the CYPs family: CYP2S1 and CYP24A1. Importantly, CYP2S1 is a major metabolizer of carcinogenic substances being relevant that hypoxia could promote this function. Interestingly, CYP24A1 limits the action of the active form of vitamin D, which is an anti\u2010proliferative factor in cancer. Our evidence shows for the first time that hypoxia can induce CYP24A1 expression, with a potential effect on cancer progression. Our contribution clarifies a particular effect of tumoral hypoxia and the implications will be useful in the understanding of the progression of cancer, the resistance to treatment and the development of alternative therapies.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cbf.3612","type":"journal-article","created":{"date-parts":[[2020,12,30]],"date-time":"2020-12-30T08:37:26Z","timestamp":1609317446000},"page":"478-487","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Hypoxia as a modulator of cytochromes <scp>P450<\/scp>: Overexpression of the cytochromes <scp>CYP2S1<\/scp> and <scp>CYP24A1<\/scp> in human liver cancer cells in hypoxia"],"prefix":"10.1002","volume":"39","author":[{"given":"Alfredo","family":"Cabrera\u2010Cano","sequence":"first","affiliation":[{"name":"Posgrado en Biolog\u00eda Experimental, Departamento de Ciencias de la Salud Universidad Aut\u00f3noma Metropolitana  Mexico City Mexico"},{"name":"Laboratorio de Oncolog\u00eda Experimental Instituto Nacional de Pediatr\u00eda  Mexico City Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8964-5782","authenticated-orcid":false,"given":"V\u00edctor Manuel","family":"D\u00e1vila\u2010Borja","sequence":"additional","affiliation":[{"name":"Laboratorio de Oncolog\u00eda Experimental Instituto Nacional de Pediatr\u00eda  Mexico City Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3269-329X","authenticated-orcid":false,"given":"Sergio","family":"Ju\u00e1rez\u2010M\u00e9ndez","sequence":"additional","affiliation":[{"name":"Laboratorio de Oncolog\u00eda Experimental Instituto Nacional de Pediatr\u00eda  Mexico City 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