<i>Allophylus africanus</i> Stem Bark Extract Modulates the Mitochondrial Apoptotic Pathway in Human Stomach Cancer Cells
The present work aimed to detail the mechanisms elicited by <i>Allophylus africanus</i> P. Beauv. stem bark extract in human stomach cancer cells and to identify the bioactives underlying the cytotoxicity. MTT reduction and LDH leakage assays allowed characterizing the cytotoxic effects...
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| Materialtyp: | Artikel |
| Språk: | English |
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MDPI AG
2023-02-01
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| Serie: | Life |
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| Länkar: | https://www.mdpi.com/2075-1729/13/2/406 |
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| author | Vera Ribeiro Federico Ferreres Andreia Oliveira Nelson G. M. Gomes Ángel Gil-Izquierdo Luísa Araújo David Pereira Patrícia Valentão |
| author_facet | Vera Ribeiro Federico Ferreres Andreia Oliveira Nelson G. M. Gomes Ángel Gil-Izquierdo Luísa Araújo David Pereira Patrícia Valentão |
| author_sort | Vera Ribeiro |
| collection | DOAJ |
| description | The present work aimed to detail the mechanisms elicited by <i>Allophylus africanus</i> P. Beauv. stem bark extract in human stomach cancer cells and to identify the bioactives underlying the cytotoxicity. MTT reduction and LDH leakage assays allowed characterizing the cytotoxic effects in AGS cells, which were further detailed by morphological analysis using phalloidin and Hoechst 33258. Proapoptotic mechanisms were elucidated through a mitochondrial membrane potential assay and by assessing the impact upon the activity of caspase-9 and -3. The extract displayed selective cytotoxicity against AGS cells. The absence of plasma membrane permeabilization, along with apoptotic body formation, suggested that pro-apoptotic effects triggered cell death. Intrinsic apoptosis pathway activation was verified, as mitochondrial membrane potential decrease and activation of caspase-9 and -3 were observed. HPLC-DAD profiling enabled the identification of two apigenin-di-<i>C</i>-glycosides, vicenin-2 (<b>1</b>) and apigenin-6<i>-C-</i>hexoside-8<i>-C-</i>pentoside (<b>3</b>), as well as three mono<i>-C-</i>glycosides-<i>O</i>-glycosylated derivatives, apigenin-7<i>-O-</i>hexoside-8<i>-C-</i>hexoside (<b>2</b>), apigenin-8<i>-C-</i>(2-rhamnosyl)hexoside (<b>4</b>) and apigenin-6<i>-C-</i>(2-rhamnosyl)hexoside (<b>5</b>). Isovitexin-2″<i>-O-</i>rhamnoside (<b>5</b>) is the main constituent, accounting for nearly 40% of the total quantifiable flavonoid content. Our results allowed us to establish the relationship between the presence of vicenin-2 and other apigenin derivatives with the contribution to the cytotoxic effects on the presented AGS cells. Our findings attest the anticancer potential of <i>A. africanus</i> stem bark against gastric adenocarcinoma, calling for studies to develop herbal-based products and/or the use of apigenin derivatives in chemotherapeutic drug development. |
| first_indexed | 2024-03-11T08:32:12Z |
| format | Article |
| id | doaj.art-1d55d85b89dd45d8856d946b17e45d28 |
| institution | Directory Open Access Journal |
| issn | 2075-1729 |
| language | English |
| last_indexed | 2024-03-11T08:32:12Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Life |
| spelling | doaj.art-1d55d85b89dd45d8856d946b17e45d282023-11-16T21:40:50ZengMDPI AGLife2075-17292023-02-0113240610.3390/life13020406<i>Allophylus africanus</i> Stem Bark Extract Modulates the Mitochondrial Apoptotic Pathway in Human Stomach Cancer CellsVera Ribeiro0Federico Ferreres1Andreia Oliveira2Nelson G. M. Gomes3Ángel Gil-Izquierdo4Luísa Araújo5David Pereira6Patrícia Valentão7REQUIMTE/LAQV, Laboratório de Farmacognosia, Departamento de Química, Faculdade de Farmácia, Universidade do Porto, R. Jorge Viterbo Ferreira, nº 228, 4050-313 Porto, PortugalDepartment of Food Technology and Nutrition, Molecular Recognition and Encapsulation (REM) Group, Universidad Católica de Murcia, UCAM, Campus Los Jerónimos, s/n, 30107 Murcia, SpainREQUIMTE/LAQV, Laboratório de Farmacognosia, Departamento de Química, Faculdade de Farmácia, Universidade do Porto, R. Jorge Viterbo Ferreira, nº 228, 4050-313 Porto, PortugalREQUIMTE/LAQV, Laboratório de Farmacognosia, Departamento de Química, Faculdade de Farmácia, Universidade do Porto, R. Jorge Viterbo Ferreira, nº 228, 4050-313 Porto, PortugalResearch Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS (CSIC), Campus University Espinardo, P.O. Box 164, 30100 Murcia, SpainMDS—Medicamentos e Diagnósticos em Saúde, Avenida dos Combatentes da Liberdade da Pátria, Bissau, Guinea-BissauREQUIMTE/LAQV, Laboratório de Farmacognosia, Departamento de Química, Faculdade de Farmácia, Universidade do Porto, R. Jorge Viterbo Ferreira, nº 228, 4050-313 Porto, PortugalREQUIMTE/LAQV, Laboratório de Farmacognosia, Departamento de Química, Faculdade de Farmácia, Universidade do Porto, R. Jorge Viterbo Ferreira, nº 228, 4050-313 Porto, PortugalThe present work aimed to detail the mechanisms elicited by <i>Allophylus africanus</i> P. Beauv. stem bark extract in human stomach cancer cells and to identify the bioactives underlying the cytotoxicity. MTT reduction and LDH leakage assays allowed characterizing the cytotoxic effects in AGS cells, which were further detailed by morphological analysis using phalloidin and Hoechst 33258. Proapoptotic mechanisms were elucidated through a mitochondrial membrane potential assay and by assessing the impact upon the activity of caspase-9 and -3. The extract displayed selective cytotoxicity against AGS cells. The absence of plasma membrane permeabilization, along with apoptotic body formation, suggested that pro-apoptotic effects triggered cell death. Intrinsic apoptosis pathway activation was verified, as mitochondrial membrane potential decrease and activation of caspase-9 and -3 were observed. HPLC-DAD profiling enabled the identification of two apigenin-di-<i>C</i>-glycosides, vicenin-2 (<b>1</b>) and apigenin-6<i>-C-</i>hexoside-8<i>-C-</i>pentoside (<b>3</b>), as well as three mono<i>-C-</i>glycosides-<i>O</i>-glycosylated derivatives, apigenin-7<i>-O-</i>hexoside-8<i>-C-</i>hexoside (<b>2</b>), apigenin-8<i>-C-</i>(2-rhamnosyl)hexoside (<b>4</b>) and apigenin-6<i>-C-</i>(2-rhamnosyl)hexoside (<b>5</b>). Isovitexin-2″<i>-O-</i>rhamnoside (<b>5</b>) is the main constituent, accounting for nearly 40% of the total quantifiable flavonoid content. Our results allowed us to establish the relationship between the presence of vicenin-2 and other apigenin derivatives with the contribution to the cytotoxic effects on the presented AGS cells. Our findings attest the anticancer potential of <i>A. africanus</i> stem bark against gastric adenocarcinoma, calling for studies to develop herbal-based products and/or the use of apigenin derivatives in chemotherapeutic drug development.https://www.mdpi.com/2075-1729/13/2/406<i>Allophylus africanus</i>EthnopharmacologyisovitexinRhamnosylvitexinSapindaceaevitexin |
| spellingShingle | Vera Ribeiro Federico Ferreres Andreia Oliveira Nelson G. M. Gomes Ángel Gil-Izquierdo Luísa Araújo David Pereira Patrícia Valentão <i>Allophylus africanus</i> Stem Bark Extract Modulates the Mitochondrial Apoptotic Pathway in Human Stomach Cancer Cells Life <i>Allophylus africanus</i> Ethnopharmacology isovitexin Rhamnosylvitexin Sapindaceae vitexin |
| title | <i>Allophylus africanus</i> Stem Bark Extract Modulates the Mitochondrial Apoptotic Pathway in Human Stomach Cancer Cells |
| title_full | <i>Allophylus africanus</i> Stem Bark Extract Modulates the Mitochondrial Apoptotic Pathway in Human Stomach Cancer Cells |
| title_fullStr | <i>Allophylus africanus</i> Stem Bark Extract Modulates the Mitochondrial Apoptotic Pathway in Human Stomach Cancer Cells |
| title_full_unstemmed | <i>Allophylus africanus</i> Stem Bark Extract Modulates the Mitochondrial Apoptotic Pathway in Human Stomach Cancer Cells |
| title_short | <i>Allophylus africanus</i> Stem Bark Extract Modulates the Mitochondrial Apoptotic Pathway in Human Stomach Cancer Cells |
| title_sort | i allophylus africanus i stem bark extract modulates the mitochondrial apoptotic pathway in human stomach cancer cells |
| topic | <i>Allophylus africanus</i> Ethnopharmacology isovitexin Rhamnosylvitexin Sapindaceae vitexin |
| url | https://www.mdpi.com/2075-1729/13/2/406 |
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