Fumonisin B1 protects against long-chained polyunsaturated fatty acid-induced cell death in HepG2 cells - implications for cancer promotion

Sylvia Riedel; Stefan Abel; Hester-Mari Burger; Sonja Swanevelder; Wentzel C A Gelderblom

doi:10.1016/j.bbamem.2024.184310

Fumonisin B₁ protects against long-chained polyunsaturated fatty acid-induced cell death in HepG2 cells - implications for cancer promotion

Biochim Biophys Acta Biomembr. 2024 Mar 11;1866(5):184310. doi: 10.1016/j.bbamem.2024.184310. Online ahead of print.

Authors

Sylvia Riedel¹, Stefan Abel², Hester-Mari Burger³, Sonja Swanevelder⁴, Wentzel C A Gelderblom⁵

Affiliations

¹ Biomedical Research and Innovation Platform, South African Medical Research Council, PO Box 19070, Tygerberg 7505, South Africa; Centre for Cardiometabolic Research in Africa (CARMA), Division of Medical Physiology, Faculty of Medicine and Health Sciences, Stellenbosch University, PO Box 241, Cape Town 8000, South Africa. Electronic address: sylvia.riedel@mrc.ac.za.
² Applied Microbial and Health Biotechnology Institute, Cape Peninsula University of Technology, PO Box 1906, Bellville 7535, South Africa. Electronic address: abels@cput.ac.za.
³ Unit of Research Integrity, Research Directorate, Cape Peninsula University of Technology, Bellville 7535, South Africa. Electronic address: burgerh@cput.ac.za.
⁴ Biostatistics Research Unit, South African Medical Research Council, PO Box 19070, Tygerberg 7505, South Africa. Electronic address: sonja.swanevelder@mrc.ac.za.
⁵ Department of Biochemistry, Stellenbosch University, Private Bag X1, Matieland 7602, South Africa.

PMID: 38479610
DOI: 10.1016/j.bbamem.2024.184310

Abstract

Fumonisin B₁ (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.

Keywords: Apoptosis; Cellular resistance; Fatty acids; Fumonisin B(1); Membrane lipids.