What question did this study set out to answer?

This research explores the effectiveness of conjugated linolenic acids in inducing ferroptosis in melanoma cells.

March 14, 2026Open Access

Conjugated Linolenic Acids Induce Ferroptosis in Human and Zebrafish Melanoma Cells

ZZZhuo ZhangUniversity of Science and Technology of China AVAlice ValemboisIFAPME CRCaroline RosierUCLouvain

Key Points

This research explores the effectiveness of conjugated linolenic acids in inducing ferroptosis in melanoma cells.
Examined toxicity of four CLnA isomers on human and zebrafish melanoma cell lines.
Assessed cell viability reductions across A375, WM266.4, and ZMEL1 cell lines.
Identified ferroptosis inhibitors to analyze their effect on CLnA-induced cell death.
Conducted fatty acid analysis to evaluate incorporation of CLnAs in phospholipids.
Observed dose-dependent reduction in cell viability across all tested cell lines.
Human melanoma cells displayed higher sensitivity to CLnAs compared to ZMEL1 cells.
Ferroptosis inhibitors reduced cell death, confirming ferroptosis as a primary death mechanism.
ACSL4 and GPX4 inhibitors influenced CLnA toxicity, underscoring their regulatory roles.

Abstract

Conjugated linolenic acids (CLnAs) are emerging as promising agents to trigger ferroptosis, a cell death driven by excessive lipid peroxidation, in cancer cells. Given the aggressive nature and treatment resistance of malignant melanoma, exploring CLnAs as therapeutic agents may offer a novel strategy to overcome these challenges. Here, we investigated the toxicity of four CLnA isomers on human (A375, WM266.4) and zebrafish (ZMEL1) melanoma cell lines. We observed a dose-dependent reduction in cell viability across all three tested cell lines. While human melanoma cells were more sensitive to CLnAs than ZMEL1 cells, treatment with ferroptosis inhibitors mitigated cell death in all models, confirming ferroptosis as the consistent primary mechanism of cell death. In addition, chemical inhibitors of ACSL4 and GPX4 modulated CLnA toxicity, further substantiating the ferroptotic mechanism by highlighting the role of these key regulators. Furthermore, fatty acid analysis revealed that CLnAs were effectively incorporated into phospholipids, generating substrates for lethal lipid peroxidation. At the transcriptional level, CLnA treatment significantly upregulated the pro-ferroptotic gene acsl4a in ZMEL1 cells. Overall, our study identifies specific CLnAs as potent ferroptosis inducers in both human and zebrafish melanoma cells and underscores the translational relevance of the zebrafish model based on a shared ferroptotic mechanism.

AI에게 질문

Bookmark

View Full Paper