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Targeting Proteolysis with Cyanogenic Glycoside Amygdalin Induces Apoptosis in Breast Cancer Cells

Background: Breast cancer is the most diagnosed cancer among women, and its incidence and mortality are rapidly growing worldwide. In this regard, plant-derived natural compounds have been shown to be effective as chemotherapeutic and preventative agents. Apricot kernels are a rich source of nutrien...

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Autores principales: Cecarini, Valentina, Selmi, Salima, Cuccioloni, Massimiliano, Gong, Chunmei, Bonfili, Laura, Zheng, Yadong, Cortese, Manuela, Angeletti, Mauro, Kilani, Soumaya, Eleuteri, Anna Maria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9657530/
https://www.ncbi.nlm.nih.gov/pubmed/36364419
http://dx.doi.org/10.3390/molecules27217591
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author Cecarini, Valentina
Selmi, Salima
Cuccioloni, Massimiliano
Gong, Chunmei
Bonfili, Laura
Zheng, Yadong
Cortese, Manuela
Angeletti, Mauro
Kilani, Soumaya
Eleuteri, Anna Maria
author_facet Cecarini, Valentina
Selmi, Salima
Cuccioloni, Massimiliano
Gong, Chunmei
Bonfili, Laura
Zheng, Yadong
Cortese, Manuela
Angeletti, Mauro
Kilani, Soumaya
Eleuteri, Anna Maria
author_sort Cecarini, Valentina
collection PubMed
description Background: Breast cancer is the most diagnosed cancer among women, and its incidence and mortality are rapidly growing worldwide. In this regard, plant-derived natural compounds have been shown to be effective as chemotherapeutic and preventative agents. Apricot kernels are a rich source of nutrients including proteins, lipids, fibers, and phenolic compounds and contain the aromatic cyanogenic glycoside amygdalin that has been shown to exert a cytotoxic effect on cancer cells by affecting the cell cycle, inducing apoptosis, and regulating the immune function. Methods: Here, we describe a previously unexplored proapoptotic mechanism of action of amygdalin in breast cancer (MCF7) cells that involves the modulation of intracellular proteolysis. For comparative purposes, the same investigations were also conducted upon cell treatment with two apricot kernel aqueous extracts from Prunus armeniaca L. Results: We observed that both the 20S and 26S proteasome activities were downregulated in the MCF7 cells upon 24 h treatments. Simultaneously, the autophagy cascade resulted in being impaired due to cathepsin B and L inhibition that also contributed to a reduction in cancer cell migration. The inhibition of these proteolytic systems finally promoted the activation of apoptotic events in the MCF7 cells. Conclusion: Collectively, our data unveil a novel mechanism of the anticancer activity of amygdalin, prompting further investigations for potential application in cancer preventative strategies.
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spelling pubmed-96575302022-11-15 Targeting Proteolysis with Cyanogenic Glycoside Amygdalin Induces Apoptosis in Breast Cancer Cells Cecarini, Valentina Selmi, Salima Cuccioloni, Massimiliano Gong, Chunmei Bonfili, Laura Zheng, Yadong Cortese, Manuela Angeletti, Mauro Kilani, Soumaya Eleuteri, Anna Maria Molecules Article Background: Breast cancer is the most diagnosed cancer among women, and its incidence and mortality are rapidly growing worldwide. In this regard, plant-derived natural compounds have been shown to be effective as chemotherapeutic and preventative agents. Apricot kernels are a rich source of nutrients including proteins, lipids, fibers, and phenolic compounds and contain the aromatic cyanogenic glycoside amygdalin that has been shown to exert a cytotoxic effect on cancer cells by affecting the cell cycle, inducing apoptosis, and regulating the immune function. Methods: Here, we describe a previously unexplored proapoptotic mechanism of action of amygdalin in breast cancer (MCF7) cells that involves the modulation of intracellular proteolysis. For comparative purposes, the same investigations were also conducted upon cell treatment with two apricot kernel aqueous extracts from Prunus armeniaca L. Results: We observed that both the 20S and 26S proteasome activities were downregulated in the MCF7 cells upon 24 h treatments. Simultaneously, the autophagy cascade resulted in being impaired due to cathepsin B and L inhibition that also contributed to a reduction in cancer cell migration. The inhibition of these proteolytic systems finally promoted the activation of apoptotic events in the MCF7 cells. Conclusion: Collectively, our data unveil a novel mechanism of the anticancer activity of amygdalin, prompting further investigations for potential application in cancer preventative strategies. MDPI 2022-11-05 /pmc/articles/PMC9657530/ /pubmed/36364419 http://dx.doi.org/10.3390/molecules27217591 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
Cecarini, Valentina
Selmi, Salima
Cuccioloni, Massimiliano
Gong, Chunmei
Bonfili, Laura
Zheng, Yadong
Cortese, Manuela
Angeletti, Mauro
Kilani, Soumaya
Eleuteri, Anna Maria
Targeting Proteolysis with Cyanogenic Glycoside Amygdalin Induces Apoptosis in Breast Cancer Cells
title Targeting Proteolysis with Cyanogenic Glycoside Amygdalin Induces Apoptosis in Breast Cancer Cells
title_full Targeting Proteolysis with Cyanogenic Glycoside Amygdalin Induces Apoptosis in Breast Cancer Cells
title_fullStr Targeting Proteolysis with Cyanogenic Glycoside Amygdalin Induces Apoptosis in Breast Cancer Cells
title_full_unstemmed Targeting Proteolysis with Cyanogenic Glycoside Amygdalin Induces Apoptosis in Breast Cancer Cells
title_short Targeting Proteolysis with Cyanogenic Glycoside Amygdalin Induces Apoptosis in Breast Cancer Cells
title_sort targeting proteolysis with cyanogenic glycoside amygdalin induces apoptosis in breast cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9657530/
https://www.ncbi.nlm.nih.gov/pubmed/36364419
http://dx.doi.org/10.3390/molecules27217591
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