1. Fumonisin B 1 protects against long-chained polyunsaturated fatty acid-induced cell death in HepG2 cells - implications for cancer promotion.
- Author
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Riedel S, Abel S, Burger HM, Swanevelder S, and Gelderblom WCA
- Subjects
- Humans, Hep G2 Cells, Oxidative Stress drug effects, Cell Survival drug effects, Cell Death drug effects, Liver Neoplasms pathology, Liver Neoplasms metabolism, Cholesterol metabolism, Fumonisins pharmacology, Fatty Acids, Unsaturated pharmacology, Fatty Acids, Unsaturated metabolism, Apoptosis drug effects
- Abstract
Fumonisin B
1 (FB1 ), a food-borne mycotoxin, is a cancer promoter in rodent liver and augments proliferation of initiated cells while inhibiting the growth of normal hepatocytes by disrupting lipid biosynthesis at various levels. HepG2 cancer cells exhibited resistance to FB1 -induced toxic effects presumably due to their low content of polyunsaturated fatty acids (PUFA) even though FB1 -typical lipid changes were observed, e.g. significantly increased phosphatidylethanolamine (PE), decreased sphingomyelin and cholesterol content, increased sphinganine (Sa) and sphinganine/sphingosine ratio, increased C18:1ω-9, decreased C20:4ω-6 content in PE and decreased C20:4ω-6_PC/PE ratio. Increasing PUFA content of HepG2 cells with phosphatidylcholine (PC) vesicles containing C20:4ω-6 (SAPC) or C22:6ω-3 (SDPC) disrupted cell survival, cellular redox status and induced oxidative stress and apoptosis. A partially protective effect of FB1 was evident in PUFA-enriched HepG2 cells which may be related to the FB1 -induced reduction in oxidative stress and the disruption of key cell membrane constituents indicative of a resistant lipid phenotype. Interactions between different ω-6 and ω-3 PUFA, membrane constituents including cholesterol, and the glycerophospho- and sphingolipids and FB1 in this cell model provide further support for the resistant lipid phenotype and its role in the complex cellular effects underlying the cancer promoting potential of the fumonisins., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)- Published
- 2024
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