Beta-Naphthoflavone Modulates CYP1A2 and Dp71 Gene Expression and Enhances the Long-Term Antiproliferative Effect of Sorafenib in HepG2 Cells
Year: 2026
Type: article
Abstract: Sorafenib (SOR) is a systemic therapy used for advanced hepatocellular carcinoma (HCC), although the therapeutic response can be limited by intrinsic or acquired resistance. β-Naphthoflavone (BNF), a synthetic flavonoid and aryl hydrocarbon receptor agonist, modulates cytochrome P450 enzymes and cancer-related pathways. In this study, we evaluated the effects of combined BNF/SOR treatment on CYP1A2 and Dp71 expression and on the viability, wound closure, invasion, and colony-forming capacity of HepG2 cells. BNF/SOR cotreatment significantly increased CYP1A2 mRNA expression, whereas no significant change in CYP1A2 protein expression was detected. SOR alone increased Dp71 mRNA expression, whereas BNF/SOR cotreatment reduced Dp71 mRNA expression relative to SOR; these changes were not detected at the protein level. SOR and BNF/SOR produced similar reductions in short-term viability and wound closure, and no statistically significant difference in invasion was detected under the conditions tested. In contrast, compared with SOR alone, BNF/SOR cotreatment resulted in a reduction in long-term colony-forming capacity. These findings reveal an association between BNF/SOR treatment, transcriptional modulation of CYP1A2 and Dp71, and reduced clonogenic capacity in HepG2 cells, without establishing causal mediation, pharmacological synergy, or reversal of sorafenib resistance.
DOI: 10.3390/cimb48111186
Language: English
Subfield: Hepatology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,654
OpenAlex ID: W7225653010
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