{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:00:32Z","timestamp":1787029232385,"version":"build-2736575974"},"reference-count":40,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,8,28]],"date-time":"2021-08-28T00:00:00Z","timestamp":1630108800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["2016\/21\/B\/NZ5\/01390"],"award-info":[{"award-number":["2016\/21\/B\/NZ5\/01390"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Increasing evidence suggests that combinations of phytochemicals are more efficient than single components in the modulation of signaling pathways involved in cancer development. In this study, the impact of phenethyl isothiocyanate (PEITC), indole-3-carbinol (I3C), xanthohumol, (X), and resveratrol (RES) and their combinations on the activation and expression of Nrf2 and NF-\u03baB in human hepatocytes and HCC cells were evaluated. Methods: THLE-2 and HepG2 cells were exposed to single phytochemicals and their combinations for 24 h. The activation of Nrf2 and NF-\u03baB, expression of their target genes, and effect on cells survival were assessed. The tumor burden was evaluated in mice carrying xenografts. Results: All phytochemicals enhanced the activation and expression of Nrf2 and its target genes SOD and NQO1 in HepG2 cells. The increased expression of NQO1 (~90%) was associated with increased ROS generation. X + PEITC downregulated NF-\u03baB activation reducing binding of its active subunits to DNA resulting in diminished COX-2 expression. In contrast to single phytochemicals, X + PEITC induced apoptosis. Moderate reduction of tumor burden in mice carrying xenografts following X and PEITC or their combination was observed. Conclusions: Since Nrf2 is overexpressed in HCC its reduced activation together with diminished level of NF-\u03baB by X + PEITC may be considered as a strategy to support conventional HCC therapy.<\/jats:p>","DOI":"10.3390\/nu13093000","type":"journal-article","created":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T04:07:28Z","timestamp":1630382848000},"page":"3000","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Comparison of the Impact of Xanthohumol and Phenethyl Isothiocyanate and Their Combination on Nrf2 and NF-\u03baB Pathways in HepG2 Cells In Vitro and Tumor Burden In Vivo"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8152-7140","authenticated-orcid":false,"given":"Marta","family":"Cykowiak","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Biochemistry, Poznan University of Medical Sciences, 4, \u015awi\u0119cickiego Street, 60-781 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7275-0298","authenticated-orcid":false,"given":"Violetta","family":"Krajka-Ku\u017aniak","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biochemistry, Poznan University of Medical Sciences, 4, \u015awi\u0119cickiego Street, 60-781 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6607-7436","authenticated-orcid":false,"given":"Robert","family":"Kleszcz","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biochemistry, Poznan University of Medical Sciences, 4, \u015awi\u0119cickiego Street, 60-781 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3606-3623","authenticated-orcid":false,"given":"Ma\u0142gorzata","family":"Kuci\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Toxicology, Poznan University of Medical Sciences, Dojazd 30, 60-631 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5875-3425","authenticated-orcid":false,"given":"Hanna","family":"Szaefer","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biochemistry, Poznan University of Medical Sciences, 4, \u015awi\u0119cickiego Street, 60-781 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Piotrowska-Kempisty","sequence":"additional","affiliation":[{"name":"Department of Toxicology, Poznan University of Medical Sciences, Dojazd 30, 60-631 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Plewi\u0144ski","sequence":"additional","affiliation":[{"name":"Centre for Advanced Technologies, Adam Mickiewicz University, 10, Uniwersytetu Pozna\u0144skiego Street, 61-614 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2903-4912","authenticated-orcid":false,"given":"Marek","family":"Murias","sequence":"additional","affiliation":[{"name":"Department of Toxicology, Poznan University of Medical Sciences, Dojazd 30, 60-631 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6625-5343","authenticated-orcid":false,"given":"Wanda","family":"Baer-Dubowska","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biochemistry, Poznan University of Medical Sciences, 4, \u015awi\u0119cickiego Street, 60-781 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/cr.2010.183","article-title":"NF-\u03baB and STAT3\u2014key players in liver inflammation and cancer","volume":"21","author":"He","year":"2010","journal-title":"Cell Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1146\/annurev-biophys-083012-130338","article-title":"Molecular Basis of NF-\u03baB Signaling","volume":"42","author":"Napetschnig","year":"2013","journal-title":"Annu. 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