Cargando…
Impact of Enniatin B and Beauvericin on Lysosomal Cathepsin B Secretion and Apoptosis Induction
Enniatin B (ENN B) and Beauvericin (BEA) are cyclohexadepsipeptides that can be isolated from Fusarium and Beauveria bassiana, respectively. Both compounds are cytotoxic and ionophoric. In the present study, the mechanism of cell death induced by these compounds was investigated. Epidermal carcinoma...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9916760/ https://www.ncbi.nlm.nih.gov/pubmed/36768354 http://dx.doi.org/10.3390/ijms24032030 |
_version_ | 1784886204212183040 |
---|---|
author | Aufy, Mohammed Abdelaziz, Ramadan F. Hussein, Ahmed M. Topcagic, Nermina Shamroukh, Hadil Abdel-Maksoud, Mostafa A. Salem, Tamer Z. Studenik, Christian R. |
author_facet | Aufy, Mohammed Abdelaziz, Ramadan F. Hussein, Ahmed M. Topcagic, Nermina Shamroukh, Hadil Abdel-Maksoud, Mostafa A. Salem, Tamer Z. Studenik, Christian R. |
author_sort | Aufy, Mohammed |
collection | PubMed |
description | Enniatin B (ENN B) and Beauvericin (BEA) are cyclohexadepsipeptides that can be isolated from Fusarium and Beauveria bassiana, respectively. Both compounds are cytotoxic and ionophoric. In the present study, the mechanism of cell death induced by these compounds was investigated. Epidermal carcinoma-derived cell line KB-3-1 cells were treated with different concentrations of these compounds. The extracellular secretion of cathepsin B increased in a concentration-dependent manner, and the lysosomal staining by lysotracker red was reduced upon the treatment with any of the compounds. However, the extracellular secretion of cathepsin L and cathepsin D were not affected. Inhibition of cathepsin B with specific inhibitor CA074 significantly reduced the cytotoxic effect of both compounds, while inhibition of cathepsin D or cathepsin L did not influence the cytotoxic activities of both compounds. In vitro labelling of lysosomal cysteine cathepsins with Ethyl (2S, 3S)-epoxysuccinate-Leu-Tyr-Acp-Lys (Biotin)-NH2 (DCG04) was not affected in case of cathepsin L upon the treatment with both compounds, while it was significantly reduced in case of cathepsin B. In conclusion, ENN B and BEA increase lysosomal Ph, which inhibits delivery of cathepsin B from Golgi to lysosomes, thereby inducing cathepsin B release in cytosol, which activates caspases and hence the apoptotic pathway. |
format | Online Article Text |
id | pubmed-9916760 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-99167602023-02-11 Impact of Enniatin B and Beauvericin on Lysosomal Cathepsin B Secretion and Apoptosis Induction Aufy, Mohammed Abdelaziz, Ramadan F. Hussein, Ahmed M. Topcagic, Nermina Shamroukh, Hadil Abdel-Maksoud, Mostafa A. Salem, Tamer Z. Studenik, Christian R. Int J Mol Sci Article Enniatin B (ENN B) and Beauvericin (BEA) are cyclohexadepsipeptides that can be isolated from Fusarium and Beauveria bassiana, respectively. Both compounds are cytotoxic and ionophoric. In the present study, the mechanism of cell death induced by these compounds was investigated. Epidermal carcinoma-derived cell line KB-3-1 cells were treated with different concentrations of these compounds. The extracellular secretion of cathepsin B increased in a concentration-dependent manner, and the lysosomal staining by lysotracker red was reduced upon the treatment with any of the compounds. However, the extracellular secretion of cathepsin L and cathepsin D were not affected. Inhibition of cathepsin B with specific inhibitor CA074 significantly reduced the cytotoxic effect of both compounds, while inhibition of cathepsin D or cathepsin L did not influence the cytotoxic activities of both compounds. In vitro labelling of lysosomal cysteine cathepsins with Ethyl (2S, 3S)-epoxysuccinate-Leu-Tyr-Acp-Lys (Biotin)-NH2 (DCG04) was not affected in case of cathepsin L upon the treatment with both compounds, while it was significantly reduced in case of cathepsin B. In conclusion, ENN B and BEA increase lysosomal Ph, which inhibits delivery of cathepsin B from Golgi to lysosomes, thereby inducing cathepsin B release in cytosol, which activates caspases and hence the apoptotic pathway. MDPI 2023-01-19 /pmc/articles/PMC9916760/ /pubmed/36768354 http://dx.doi.org/10.3390/ijms24032030 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Aufy, Mohammed Abdelaziz, Ramadan F. Hussein, Ahmed M. Topcagic, Nermina Shamroukh, Hadil Abdel-Maksoud, Mostafa A. Salem, Tamer Z. Studenik, Christian R. Impact of Enniatin B and Beauvericin on Lysosomal Cathepsin B Secretion and Apoptosis Induction |
title | Impact of Enniatin B and Beauvericin on Lysosomal Cathepsin B Secretion and Apoptosis Induction |
title_full | Impact of Enniatin B and Beauvericin on Lysosomal Cathepsin B Secretion and Apoptosis Induction |
title_fullStr | Impact of Enniatin B and Beauvericin on Lysosomal Cathepsin B Secretion and Apoptosis Induction |
title_full_unstemmed | Impact of Enniatin B and Beauvericin on Lysosomal Cathepsin B Secretion and Apoptosis Induction |
title_short | Impact of Enniatin B and Beauvericin on Lysosomal Cathepsin B Secretion and Apoptosis Induction |
title_sort | impact of enniatin b and beauvericin on lysosomal cathepsin b secretion and apoptosis induction |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9916760/ https://www.ncbi.nlm.nih.gov/pubmed/36768354 http://dx.doi.org/10.3390/ijms24032030 |
work_keys_str_mv | AT aufymohammed impactofenniatinbandbeauvericinonlysosomalcathepsinbsecretionandapoptosisinduction AT abdelazizramadanf impactofenniatinbandbeauvericinonlysosomalcathepsinbsecretionandapoptosisinduction AT husseinahmedm impactofenniatinbandbeauvericinonlysosomalcathepsinbsecretionandapoptosisinduction AT topcagicnermina impactofenniatinbandbeauvericinonlysosomalcathepsinbsecretionandapoptosisinduction AT shamroukhhadil impactofenniatinbandbeauvericinonlysosomalcathepsinbsecretionandapoptosisinduction AT abdelmaksoudmostafaa impactofenniatinbandbeauvericinonlysosomalcathepsinbsecretionandapoptosisinduction AT salemtamerz impactofenniatinbandbeauvericinonlysosomalcathepsinbsecretionandapoptosisinduction AT studenikchristianr impactofenniatinbandbeauvericinonlysosomalcathepsinbsecretionandapoptosisinduction |