Probing the Mechanism of Action of Cry41Aa on HepG2 through the Establishment of a Resistant Subline
Cry41Aa, also called parasporin-3, belongs to a group of toxins from the entomopathogenic bacterium <i>Bacillus thuringiensis</i> that show activity against human cancer cells. Cry41Aa exhibits preferential cytocidal activity towards HL-60 (human promyelocytic leukaemia cells) and HepG2...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-04-01
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| Series: | Toxins |
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| Online Access: | https://www.mdpi.com/2072-6651/14/5/319 |
| _version_ | 1797494929995333632 |
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| author | Wided Souissi Tweedie Alistair Barbara Domanska Eva Fortea Michelle J. West Jean-Louis Schwartz Neil Crickmore |
| author_facet | Wided Souissi Tweedie Alistair Barbara Domanska Eva Fortea Michelle J. West Jean-Louis Schwartz Neil Crickmore |
| author_sort | Wided Souissi |
| collection | DOAJ |
| description | Cry41Aa, also called parasporin-3, belongs to a group of toxins from the entomopathogenic bacterium <i>Bacillus thuringiensis</i> 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. |
| first_indexed | 2024-03-10T01:41:18Z |
| format | Article |
| id | doaj.art-5f9f4924240f4dfbb286378236fce861 |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-03-10T01:41:18Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-5f9f4924240f4dfbb286378236fce8612023-11-23T13:22:49ZengMDPI AGToxins2072-66512022-04-0114531910.3390/toxins14050319Probing the Mechanism of Action of Cry41Aa on HepG2 through the Establishment of a Resistant SublineWided Souissi0Tweedie Alistair1Barbara Domanska2Eva Fortea3Michelle J. West4Jean-Louis Schwartz5Neil Crickmore6School of Life Sciences, University of Sussex, Brighton BN1 9QG, UKSchool of Life Sciences, University of Sussex, Brighton BN1 9QG, UKSchool of Life Sciences, University of Sussex, Brighton BN1 9QG, UKDepartement of Pharmacology et Physiology, University of Montreal, Montreal, QC H3C 3J7, CanadaSchool of Life Sciences, University of Sussex, Brighton BN1 9QG, UKDepartement of Pharmacology et Physiology, University of Montreal, Montreal, QC H3C 3J7, CanadaSchool of Life Sciences, University of Sussex, Brighton BN1 9QG, UKCry41Aa, also called parasporin-3, belongs to a group of toxins from the entomopathogenic bacterium <i>Bacillus thuringiensis</i> 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.https://www.mdpi.com/2072-6651/14/5/319cry toxinparasporinHepG2AQP9 |
| spellingShingle | Wided Souissi Tweedie Alistair Barbara Domanska Eva Fortea Michelle J. West Jean-Louis Schwartz Neil Crickmore Probing the Mechanism of Action of Cry41Aa on HepG2 through the Establishment of a Resistant Subline Toxins cry toxin parasporin HepG2 AQP9 |
| title | Probing the Mechanism of Action of Cry41Aa on HepG2 through the Establishment of a Resistant Subline |
| title_full | Probing the Mechanism of Action of Cry41Aa on HepG2 through the Establishment of a Resistant Subline |
| title_fullStr | Probing the Mechanism of Action of Cry41Aa on HepG2 through the Establishment of a Resistant Subline |
| title_full_unstemmed | Probing the Mechanism of Action of Cry41Aa on HepG2 through the Establishment of a Resistant Subline |
| title_short | Probing the Mechanism of Action of Cry41Aa on HepG2 through the Establishment of a Resistant Subline |
| title_sort | probing the mechanism of action of cry41aa on hepg2 through the establishment of a resistant subline |
| topic | cry toxin parasporin HepG2 AQP9 |
| url | https://www.mdpi.com/2072-6651/14/5/319 |
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