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Synthetic Analogs of Marine Alkaloid Aplysinopsin Suppress Anti-Apoptotic Protein BCL2 in Prostate Cancer
Aplysinopsins are a class of indole alkaloids that possess various pharmacological activities. Although their action has been studied in regard to many diseases, their effect on prostate cancer has not yet been examined. Therefore, we synthesized a new series of aplysinopsin analogs and investigated...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9821956/ https://www.ncbi.nlm.nih.gov/pubmed/36615305 http://dx.doi.org/10.3390/molecules28010109 |
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author | El-Sawy, Eslam R. El-Shahid, Zeinab A. Soliman, Ahmed A. F. Nassrallah, Amr Abdelwahab, Ahmed B. Kirsch, Gilbert Abdelmegeed, Heba |
author_facet | El-Sawy, Eslam R. El-Shahid, Zeinab A. Soliman, Ahmed A. F. Nassrallah, Amr Abdelwahab, Ahmed B. Kirsch, Gilbert Abdelmegeed, Heba |
author_sort | El-Sawy, Eslam R. |
collection | PubMed |
description | Aplysinopsins are a class of indole alkaloids that possess various pharmacological activities. Although their action has been studied in regard to many diseases, their effect on prostate cancer has not yet been examined. Therefore, we synthesized a new series of aplysinopsin analogs and investigated their cytotoxic activity against prostate cancer. Five analogs showed high antitumor activity via suppressing the expression of the anti-apoptotic gene Bcl2, simulationously increasing the expression of the pro-apoptotic genes p53, Bax and Caspase 3. The inhibition of BCL2 led to the activation of BAX, which in turn activated Caspase 3, leading to apoptosis. This dual mechanism of action via apoptosis and cell cycle arrest induction is responsible for aplysinopsin analogs antitumor activity. Hence, our newly synthesized analogs are highly promising candidates for further preclinical studies against prostate cancer. |
format | Online Article Text |
id | pubmed-9821956 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-98219562023-01-07 Synthetic Analogs of Marine Alkaloid Aplysinopsin Suppress Anti-Apoptotic Protein BCL2 in Prostate Cancer El-Sawy, Eslam R. El-Shahid, Zeinab A. Soliman, Ahmed A. F. Nassrallah, Amr Abdelwahab, Ahmed B. Kirsch, Gilbert Abdelmegeed, Heba Molecules Article Aplysinopsins are a class of indole alkaloids that possess various pharmacological activities. Although their action has been studied in regard to many diseases, their effect on prostate cancer has not yet been examined. Therefore, we synthesized a new series of aplysinopsin analogs and investigated their cytotoxic activity against prostate cancer. Five analogs showed high antitumor activity via suppressing the expression of the anti-apoptotic gene Bcl2, simulationously increasing the expression of the pro-apoptotic genes p53, Bax and Caspase 3. The inhibition of BCL2 led to the activation of BAX, which in turn activated Caspase 3, leading to apoptosis. This dual mechanism of action via apoptosis and cell cycle arrest induction is responsible for aplysinopsin analogs antitumor activity. Hence, our newly synthesized analogs are highly promising candidates for further preclinical studies against prostate cancer. MDPI 2022-12-23 /pmc/articles/PMC9821956/ /pubmed/36615305 http://dx.doi.org/10.3390/molecules28010109 Text en © 2022 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 El-Sawy, Eslam R. El-Shahid, Zeinab A. Soliman, Ahmed A. F. Nassrallah, Amr Abdelwahab, Ahmed B. Kirsch, Gilbert Abdelmegeed, Heba Synthetic Analogs of Marine Alkaloid Aplysinopsin Suppress Anti-Apoptotic Protein BCL2 in Prostate Cancer |
title | Synthetic Analogs of Marine Alkaloid Aplysinopsin Suppress Anti-Apoptotic Protein BCL2 in Prostate Cancer |
title_full | Synthetic Analogs of Marine Alkaloid Aplysinopsin Suppress Anti-Apoptotic Protein BCL2 in Prostate Cancer |
title_fullStr | Synthetic Analogs of Marine Alkaloid Aplysinopsin Suppress Anti-Apoptotic Protein BCL2 in Prostate Cancer |
title_full_unstemmed | Synthetic Analogs of Marine Alkaloid Aplysinopsin Suppress Anti-Apoptotic Protein BCL2 in Prostate Cancer |
title_short | Synthetic Analogs of Marine Alkaloid Aplysinopsin Suppress Anti-Apoptotic Protein BCL2 in Prostate Cancer |
title_sort | synthetic analogs of marine alkaloid aplysinopsin suppress anti-apoptotic protein bcl2 in prostate cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9821956/ https://www.ncbi.nlm.nih.gov/pubmed/36615305 http://dx.doi.org/10.3390/molecules28010109 |
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