What question did this study set out to answer?

The aim is to explore how CYP2E1 influences ferroptosis and its implications for hepatocellular carcinoma treatment.

April 5, 2026

Abstract 2413: Insights in CYP2E1-mediated ferroptosis in hepatocellular carcinoma

Key Points

The aim is to explore how CYP2E1 influences ferroptosis and its implications for hepatocellular carcinoma treatment.
Cultured HCC cell lines according to ATCC guidelines.
Transduced cells with adenoviral vectors expressing CYP2E1 and confirmed expression via Western Blot.
Treated cells with palmitic acid (0-5mM) for toxicity assessment and analyzed cell death.
Exposed cells to ferroptosis inducers at graded concentrations for cell death analysis.
Cells showed varied sensitivity to palmitic acid, with HepG2 cells responding more strongly than others.
CYP2E1 expression did not significantly affect sensitivity to palmitic acid.
Sensitivity to ferroptosis inducers varied markedly across cell lines, indicating a cell type-specific response.

Abstract

Abstract Introduction: CYP2E1, a cytochrome P450 enzyme mainly found in hepatocytes, is crucial for metabolizing xenobiotics including fatty acids and drugs. In hepatocellular carcinoma (HCC), CYP2E1 acts as a tumor suppressor. However, CYP2E1 has significantly reduced RNA and protein expression in HCC and its expression correlates positively with patient survival. We hypothesized that CYP2E1 promotes ferroptosis—a regulated, iron-dependent cell death involving iron accumulation, ROS generation, glutathione depletion, and lipid peroxidation—which may underlie its beneficial effects in HCC. Methods: HCC cell lines were cultured per ATCC guidelines and transduced with adenoviral vectors expressing GFP or CYP2E1, confirmed by Western Blot. To assess palmitic acid (PA) toxicity, cells were treated with 0-5mM PA for 24 and 48h, followed by cell death analysis. For ferroptosis sensitivity, cells were exposed to graded concentrations of inducers (FINO2, FIN56, Erastin, RSL3) for 24h, then analyzed for cell death. Results: Cell lines exhibited a variation in sensitivity to palmitic acid (PA) treatment, with HepG2 exhibiting a stronger response than SNU398 and SNU449 cells. However, there was no statistically significant effect of CYP2E1 expression in the response to PA feeding. Sensitivity to ferroptosis inducers also varied widely across cell lines and appeared to be cell type-specific rather than dependent on CYP2E1 expression. Conclusion: Our results provide new insight into the sensitivity of different HCC cell lines to ferroptosis induced by PA feeding and by pharmacological inducers of ferroptosis. Further studies are needed to determine the mechanism of CYP2E1 tumor suppression, which our data suggests may not be through ferroptosis. Citation Format: Kristy L. Thomas, Kylie R. Driggers, Hyland C. Gonzalex, Jessica H. Hartman. Insights in CYP2E1-mediated ferroptosis in hepatocellular carcinoma abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2413.

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