Effects of Annona muricata Extract on Triple-Negative Breast Cancer Cells Mediated Through EGFR Signaling
Heba K Alshaeri,1,2 Moudi M Alasmari,3,4 Zuhair S Natto,5 Alejandro Pino-Figueroa2 1Department of Pharmaceutical Sciences, Fakeeh College for Medical Sciences, Jeddah, Saudi Arabia; 2Department of Pharmaceutical Sciences, MCPHS University, Boston, MA, USA; 3College of Medicine, King Saud Bin Abdulaz...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2020-12-01
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| Series: | Cancer Management and Research |
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| Online Access: | https://www.dovepress.com/effects-of-annona-muricata-extract-on-triple-negative-breast-cancer-ce-peer-reviewed-article-CMAR |
| _version_ | 1818390190536785920 |
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| author | Alshaeri HK Alasmari MM Natto ZS Pino-Figueroa A |
| author_facet | Alshaeri HK Alasmari MM Natto ZS Pino-Figueroa A |
| author_sort | Alshaeri HK |
| collection | DOAJ |
| description | Heba K Alshaeri,1,2 Moudi M Alasmari,3,4 Zuhair S Natto,5 Alejandro Pino-Figueroa2 1Department of Pharmaceutical Sciences, Fakeeh College for Medical Sciences, Jeddah, Saudi Arabia; 2Department of Pharmaceutical Sciences, MCPHS University, Boston, MA, USA; 3College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia; 4King Abdullah International Research Center, Jeddah, Saudi Arabia; 5Department of Dental Public Health, Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi ArabiaCorrespondence: Heba K AlshaeriDepartment of Pharmaceutical Sciences, Fakeeh College for Medical Sciences, Jeddah 21499, Saudi ArabiaTel +966 504691039Fax +966 12 6943899Email hkalshaeri@fcms.edu.saPurpose: To evaluate the antiproliferative activity and the mechanisms of action of Annona muricata ethyl acetate (AMEA) extract and one of its active fractions on BT-20 TNBC cells.Methods: The triple-negative human breast cancer BT-20 cells were used. After the preparation and extraction of Annona muricata ethyl acetate (AMEA), the ethyl acetate extract was exposed to a preparative thin layer chromatography (TLC) plate. From this preparative TLC plate, eight individual bands were collected. Each band was scraped and removed from the plate and soaked in ethyl acetate. After filtration, all eight fractions were then tested on the BT-20 TNBC cells using the MTS cell viability assay. The expressions of EGFR, p-EGFR, AKT, p-AKT, MAPK, p-MAPK, cyclin D1, and NF-κB p65 were measured using Western blot analysis.Results: The AMEA showed a significant decrease in NF-κB p65 protein expression and BT-20 cell viability, as determined via the MTS assay. Furthermore, the AMEA was subjected to preparative thin layer chromatography (TLC), and eight fractions were obtained. From the eight fractions, only fraction 4 (F4) showed a significant reduction in cell viability in the MTS assay. Immunoblotting analysis revealed that AMEA and F4 formed an antiproliferative effect. These effects were complemented by a downregulation of cyclin D1 assembly, causing cell-cycle arrest at the G1/S phase. Furthermore, NF-κB was measured because of its involvement in the progression of cancers.Conclusion: The antiproliferative influence is produced through EGFR-mediated signaling pathways, which include AKT, MAPK, NF-κB, and cyclin D1 inhibition. Further studies will be required to demonstrate the possible applications of this natural product in breast cancer therapy.Keywords: triple negative, breast cancer, Annona muricata, acetogenins |
| first_indexed | 2024-12-14T04:53:41Z |
| format | Article |
| id | doaj.art-a4f0b499acee4884b9c7c2099e9ce0ac |
| institution | Directory Open Access Journal |
| issn | 1179-1322 |
| language | English |
| last_indexed | 2024-12-14T04:53:41Z |
| publishDate | 2020-12-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Cancer Management and Research |
| spelling | doaj.art-a4f0b499acee4884b9c7c2099e9ce0ac2022-12-21T23:16:28ZengDove Medical PressCancer Management and Research1179-13222020-12-01Volume 12125191252660001Effects of Annona muricata Extract on Triple-Negative Breast Cancer Cells Mediated Through EGFR SignalingAlshaeri HKAlasmari MMNatto ZSPino-Figueroa AHeba K Alshaeri,1,2 Moudi M Alasmari,3,4 Zuhair S Natto,5 Alejandro Pino-Figueroa2 1Department of Pharmaceutical Sciences, Fakeeh College for Medical Sciences, Jeddah, Saudi Arabia; 2Department of Pharmaceutical Sciences, MCPHS University, Boston, MA, USA; 3College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia; 4King Abdullah International Research Center, Jeddah, Saudi Arabia; 5Department of Dental Public Health, Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi ArabiaCorrespondence: Heba K AlshaeriDepartment of Pharmaceutical Sciences, Fakeeh College for Medical Sciences, Jeddah 21499, Saudi ArabiaTel +966 504691039Fax +966 12 6943899Email hkalshaeri@fcms.edu.saPurpose: To evaluate the antiproliferative activity and the mechanisms of action of Annona muricata ethyl acetate (AMEA) extract and one of its active fractions on BT-20 TNBC cells.Methods: The triple-negative human breast cancer BT-20 cells were used. After the preparation and extraction of Annona muricata ethyl acetate (AMEA), the ethyl acetate extract was exposed to a preparative thin layer chromatography (TLC) plate. From this preparative TLC plate, eight individual bands were collected. Each band was scraped and removed from the plate and soaked in ethyl acetate. After filtration, all eight fractions were then tested on the BT-20 TNBC cells using the MTS cell viability assay. The expressions of EGFR, p-EGFR, AKT, p-AKT, MAPK, p-MAPK, cyclin D1, and NF-κB p65 were measured using Western blot analysis.Results: The AMEA showed a significant decrease in NF-κB p65 protein expression and BT-20 cell viability, as determined via the MTS assay. Furthermore, the AMEA was subjected to preparative thin layer chromatography (TLC), and eight fractions were obtained. From the eight fractions, only fraction 4 (F4) showed a significant reduction in cell viability in the MTS assay. Immunoblotting analysis revealed that AMEA and F4 formed an antiproliferative effect. These effects were complemented by a downregulation of cyclin D1 assembly, causing cell-cycle arrest at the G1/S phase. Furthermore, NF-κB was measured because of its involvement in the progression of cancers.Conclusion: The antiproliferative influence is produced through EGFR-mediated signaling pathways, which include AKT, MAPK, NF-κB, and cyclin D1 inhibition. Further studies will be required to demonstrate the possible applications of this natural product in breast cancer therapy.Keywords: triple negative, breast cancer, Annona muricata, acetogeninshttps://www.dovepress.com/effects-of-annona-muricata-extract-on-triple-negative-breast-cancer-ce-peer-reviewed-article-CMARtriple negativebreast cancerannona muricataacetigenins. |
| spellingShingle | Alshaeri HK Alasmari MM Natto ZS Pino-Figueroa A Effects of Annona muricata Extract on Triple-Negative Breast Cancer Cells Mediated Through EGFR Signaling Cancer Management and Research triple negative breast cancer annona muricata acetigenins. |
| title | Effects of Annona muricata Extract on Triple-Negative Breast Cancer Cells Mediated Through EGFR Signaling |
| title_full | Effects of Annona muricata Extract on Triple-Negative Breast Cancer Cells Mediated Through EGFR Signaling |
| title_fullStr | Effects of Annona muricata Extract on Triple-Negative Breast Cancer Cells Mediated Through EGFR Signaling |
| title_full_unstemmed | Effects of Annona muricata Extract on Triple-Negative Breast Cancer Cells Mediated Through EGFR Signaling |
| title_short | Effects of Annona muricata Extract on Triple-Negative Breast Cancer Cells Mediated Through EGFR Signaling |
| title_sort | effects of annona muricata extract on triple negative breast cancer cells mediated through egfr signaling |
| topic | triple negative breast cancer annona muricata acetigenins. |
| url | https://www.dovepress.com/effects-of-annona-muricata-extract-on-triple-negative-breast-cancer-ce-peer-reviewed-article-CMAR |
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