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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MDPI AG
2022-11-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/21/7591 |
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| author | Valentina Cecarini Salima Selmi Massimiliano Cuccioloni Chunmei Gong Laura Bonfili Yadong Zheng Manuela Cortese Mauro Angeletti Soumaya Kilani Anna Maria Eleuteri |
| author_facet | Valentina Cecarini Salima Selmi Massimiliano Cuccioloni Chunmei Gong Laura Bonfili Yadong Zheng Manuela Cortese Mauro Angeletti Soumaya Kilani Anna Maria Eleuteri |
| author_sort | Valentina Cecarini |
| collection | DOAJ |
| 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 <i>Prunus armeniaca</i> 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. |
| first_indexed | 2024-03-09T18:48:24Z |
| format | Article |
| id | doaj.art-ddd69cd4b9c5407f8a117ff5ca6a552e |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T18:48:24Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-ddd69cd4b9c5407f8a117ff5ca6a552e2023-11-24T06:06:47ZengMDPI AGMolecules1420-30492022-11-012721759110.3390/molecules27217591Targeting Proteolysis with Cyanogenic Glycoside Amygdalin Induces Apoptosis in Breast Cancer CellsValentina Cecarini0Salima Selmi1Massimiliano Cuccioloni2Chunmei Gong3Laura Bonfili4Yadong Zheng5Manuela Cortese6Mauro Angeletti7Soumaya Kilani8Anna Maria Eleuteri9School of Biosciences and Veterinary Medicine, University of Camerino, Via Gentile III da Varano, 62032 Camerino, ItalyResearch Unit for Bioactive Natural Products and Biotechnology UR17ES49, Faculty of Dental Medicine of Monastir, University of Monastir, Avicenne Street, Monastir 5000, TunisiaSchool of Biosciences and Veterinary Medicine, University of Camerino, Via Gentile III da Varano, 62032 Camerino, ItalySchool of Biosciences and Veterinary Medicine, University of Camerino, Via Gentile III da Varano, 62032 Camerino, ItalySchool of Biosciences and Veterinary Medicine, University of Camerino, Via Gentile III da Varano, 62032 Camerino, ItalySchool of Biosciences and Veterinary Medicine, University of Camerino, Via Gentile III da Varano, 62032 Camerino, ItalyCHiP Research Center, School of Pharmacy, University of Camerino, Via Madonna delle Carceri, 62032 Camerino, ItalySchool of Biosciences and Veterinary Medicine, University of Camerino, Via Gentile III da Varano, 62032 Camerino, ItalyResearch Unit for Bioactive Natural Products and Biotechnology UR17ES49, Faculty of Dental Medicine of Monastir, University of Monastir, Avicenne Street, Monastir 5000, TunisiaSchool of Biosciences and Veterinary Medicine, University of Camerino, Via Gentile III da Varano, 62032 Camerino, ItalyBackground: 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 <i>Prunus armeniaca</i> 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.https://www.mdpi.com/1420-3049/27/21/7591amygdalinproteasomeautophagyapoptosiscancerapricot kernel extract |
| spellingShingle | Valentina Cecarini Salima Selmi Massimiliano Cuccioloni Chunmei Gong Laura Bonfili Yadong Zheng Manuela Cortese Mauro Angeletti Soumaya Kilani Anna Maria Eleuteri Targeting Proteolysis with Cyanogenic Glycoside Amygdalin Induces Apoptosis in Breast Cancer Cells Molecules amygdalin proteasome autophagy apoptosis cancer apricot kernel extract |
| 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 | amygdalin proteasome autophagy apoptosis cancer apricot kernel extract |
| url | https://www.mdpi.com/1420-3049/27/21/7591 |
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