Probing the mechanism of action of Cry41Aa on HepG2 through the establishment of a resistant subline

Souissi, Wided, Alistair, Tweedie, Domanska, Barbara, Fortea, Eva, West, Michelle J, Schwartz, Jean-Louis and Crickmore, Neil (2022) Probing the mechanism of action of Cry41Aa on HepG2 through the establishment of a resistant subline. Toxins, 14 (5). a319 1-16. ISSN 2072-6651

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Abstract

Cry41Aa, also called parasporin-3, belongs to a group of toxins from the entomopathogenic bacterium Bacillus thuringiensis that show activity against human cancer cells. Cry41Aa exhibits preferential cytocidal activity towards HL-60 (human promyelocytic leukaemia cells) and HepG2 (human liver cancer cells) cell lines after being proteolytically activated. To better understand the mechanism of action of Cry41Aa, we evolved resistance in HepG2 cells through repeated exposure to increasing doses of the toxin. Concentrations of Cry41Aa that killed over 50% of the parental HepG2 cells had no significant effect on the viability of the resistant cells and did not induce either pore formation or p38 phosphorylation (both characteristic features of pore-forming toxins). Preliminary RNA sequencing data identified AQP9 as a potential mediator of resistance, but extensive investigations failed to show a causal link and did not support an enhanced cell repair process as the resistance mechanism.

Item Type: Article
Keywords: Cancer, Liver Disease, Vaccine Related, Digestive Diseases, 2.1 Biological and endogenous factors, 5.1 Pharmaceuticals, Cancer
Schools and Departments: School of Life Sciences > Biochemistry
SWORD Depositor: Mx Elements Account
Depositing User: Mx Elements Account
Date Deposited: 11 May 2022 06:52
Last Modified: 11 May 2022 07:00
URI: http://sro.sussex.ac.uk/id/eprint/105812

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