toxins-14-00319-v2.pdf (4.38 MB)
Probing the mechanism of action of Cry41Aa on HepG2 through the establishment of a resistant subline
journal contribution
posted on 2023-06-10, 03:29 authored by Wided Souissi, Alistair Tweedie, Barbara Domanska, Eva Fortea, Michelle WestMichelle West, Jean-Louis Schwartz, Neil CrickmoreNeil CrickmoreCry41Aa, 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.
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Publication status
- Published
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- Published version
Journal
ToxinsISSN
2072-6651Publisher
MDPIExternal DOI
Issue
5Volume
14Page range
1-16Article number
a319Department affiliated with
- Biochemistry Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2022-05-11First Open Access (FOA) Date
2022-05-11First Compliant Deposit (FCD) Date
2022-05-11Usage metrics
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