Ivan Gonzalez-Chavarria, Felix Duprat, Francisco J. Roa, Nery Jara, Jorge R. Toledo, Felipe Miranda, Jose Becerra, Alejandro Inostroza, Alexandra Kelling, Uwe Schilde, Matthias Heydenreich, Cristian Paz
- Maytenus disticha (Hook F.), belonging to the Celastraceae family, is an evergreen shrub, native of the central southern mountains of Chile. Previous studies demonstrated that the total extract of M. disticha (MD) has an acetylcholinesterase inhibitory activity along with growth regulatory and insecticidal activities. beta-Dihydroagarofurans sesquiterpenes are the most active components in the plant. However, its activity in cancer has not been analyzed yet. Here, we demonstrate that MD has a cytotoxic activity on breast (MCF-7), lung (PC9), and prostate (C4-2B) human cancer cells with an IC50 (mu g/mL) of 40, 4.7, and 5 mu g/mL, respectively, an increasing Bax/Bcl2 ratio, and inducing a mitochondrial membrane depolarization. The beta-dihydroagarofuran-type sesquiterpene (MD-6), dihydromyricetin (MD-9), and dihydromyricetin-3-O-beta-glucoside (MD-10) were isolated as the major compounds from MD extracts. From these compounds, only MD-6 showed cytotoxic activity on MCF-7, PC9, and C4-2B with an IC50 of 31.02, 17.58, and 42.19 mu M,Maytenus disticha (Hook F.), belonging to the Celastraceae family, is an evergreen shrub, native of the central southern mountains of Chile. Previous studies demonstrated that the total extract of M. disticha (MD) has an acetylcholinesterase inhibitory activity along with growth regulatory and insecticidal activities. beta-Dihydroagarofurans sesquiterpenes are the most active components in the plant. However, its activity in cancer has not been analyzed yet. Here, we demonstrate that MD has a cytotoxic activity on breast (MCF-7), lung (PC9), and prostate (C4-2B) human cancer cells with an IC50 (mu g/mL) of 40, 4.7, and 5 mu g/mL, respectively, an increasing Bax/Bcl2 ratio, and inducing a mitochondrial membrane depolarization. The beta-dihydroagarofuran-type sesquiterpene (MD-6), dihydromyricetin (MD-9), and dihydromyricetin-3-O-beta-glucoside (MD-10) were isolated as the major compounds from MD extracts. From these compounds, only MD-6 showed cytotoxic activity on MCF-7, PC9, and C4-2B with an IC50 of 31.02, 17.58, and 42.19 mu M, respectively. Furthermore, the MD-6 increases cell ROS generation, and MD and MD-6 induce a mitochondrial superoxide generation and apoptosis on MCF-7, PC9, and C4-2B, which suggests that the cytotoxic effect of MD is mediated in part by the beta-dihydroagarofuran-type that induces apoptosis by a mitochondrial dysfunction.…
MetadatenAuthor details: | Ivan Gonzalez-ChavarriaORCiD, Felix Duprat, Francisco J. Roa, Nery JaraORCiD, Jorge R. ToledoORCiD, Felipe Miranda, Jose Becerra, Alejandro Inostroza, Alexandra Kelling, Uwe SchildeORCiDGND, Matthias HeydenreichORCiD, Cristian PazORCiD |
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DOI: | https://doi.org/10.3390/biom10030377 |
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ISSN: | 2218-273X |
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Pubmed ID: | https://pubmed.ncbi.nlm.nih.gov/32121436 |
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Title of parent work (English): | Biomolecules |
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Publisher: | MDPI |
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Place of publishing: | Basel |
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Publication type: | Article |
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Language: | English |
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Date of first publication: | 2020/02/29 |
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Publication year: | 2020 |
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Release date: | 2023/07/14 |
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Tag: | Maytenus disticha; Mitochondrial ROS; activity; beta-dihydroagarofuran-type sesquiterpene; cytotoxic; dihydromyricetin; dihydromyricetin-3-O-beta-glucoside |
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Volume: | 10 |
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Issue: | 3 |
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Article number: | 377 |
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Number of pages: | 15 |
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Funding institution: | Universidad de La Frontera [DI17-0049]; CONICYT ChileComision Nacional; de Investigacion Cientifica y Tecnologica (CONICYT) [REDI170107]; Universidad de Concepcion [INV 219.111.067] |
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Organizational units: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Chemie |
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DDC classification: | 5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften |
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Peer review: | Referiert |
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Publishing method: | Open Access / Gold Open-Access |
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| DOAJ gelistet |
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License (German): | CC-BY - Namensnennung 4.0 International |
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