Cytotoxic Mechanism of Sphaerodactylomelol, an Uncommon Bromoditerpene Isolated from <i>Sphaerococcus coronopifolius</i>
Marine natural products have exhibited uncommon chemical structures with relevant antitumor properties highlighting their potential to inspire the development of new anticancer agents. The goal of this work was to study the antitumor activities of the brominated diterpene sphaerodactylomelol, a rare...
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MDPI AG
2021-03-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/5/1374 |
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| author | Celso Alves Joana Silva Susete Pinteus Eva Alonso Rebeca Alvariño Adriana Duarte Diorge Marmitt Márcia Inês Goettert Helena Gaspar Amparo Alfonso Maria C. Alpoim Luis M. Botana Rui Pedrosa |
| author_facet | Celso Alves Joana Silva Susete Pinteus Eva Alonso Rebeca Alvariño Adriana Duarte Diorge Marmitt Márcia Inês Goettert Helena Gaspar Amparo Alfonso Maria C. Alpoim Luis M. Botana Rui Pedrosa |
| author_sort | Celso Alves |
| collection | DOAJ |
| description | Marine natural products have exhibited uncommon chemical structures with relevant antitumor properties highlighting their potential to inspire the development of new anticancer agents. The goal of this work was to study the antitumor activities of the brominated diterpene sphaerodactylomelol, a rare example of the dactylomelane family. Cytotoxicity (10–100 µM; 24 h) was evaluated on tumor cells (A549, CACO-2, HCT-15, MCF-7, NCI-H226, PC-3, SH-SY5Y, SK-ML-28) and the effects estimated by MTT assay. Hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) levels and apoptosis biomarkers (membrane translocation of phosphatidylserine, depolarization of mitochondrial membrane potential, Caspase-9 activity, and DNA condensation and/or fragmentation) were studied in the breast adenocarcinoma cellular model (MCF-7) and its genotoxicity on mouse fibroblasts (L929). Sphaerodactylomelol displayed an IC<sub>50</sub> range between 33.04 and 89.41 µM without selective activity for a specific tumor tissue. The cells’ viability decrease was accompanied by an increase on H<sub>2</sub>O<sub>2</sub> production, a depolarization of mitochondrial membrane potential and an increase of Caspase-9 activity and DNA fragmentation. However, the DNA damage studies in L929 non-malignant cell line suggested that this compound is not genotoxic for normal fibroblasts. Overall, the results suggest that the cytotoxicity of sphaerodactylomelol seems to be mediated by an increase of H<sub>2</sub>O<sub>2</sub> levels and downstream apoptosis. |
| first_indexed | 2024-03-09T05:35:48Z |
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| id | doaj.art-a26adad49aeb4c74b14a20712dd86d69 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T05:35:48Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-a26adad49aeb4c74b14a20712dd86d692023-12-03T12:29:10ZengMDPI AGMolecules1420-30492021-03-01265137410.3390/molecules26051374Cytotoxic Mechanism of Sphaerodactylomelol, an Uncommon Bromoditerpene Isolated from <i>Sphaerococcus coronopifolius</i>Celso Alves0Joana Silva1Susete Pinteus2Eva Alonso3Rebeca Alvariño4Adriana Duarte5Diorge Marmitt6Márcia Inês Goettert7Helena Gaspar8Amparo Alfonso9Maria C. Alpoim10Luis M. Botana11Rui Pedrosa12MARE—Marine and Environmental Sciences Centre, Politécnico de Leiria, 2520-630 Peniche, PortugalMARE—Marine and Environmental Sciences Centre, Politécnico de Leiria, 2520-630 Peniche, PortugalMARE—Marine and Environmental Sciences Centre, Politécnico de Leiria, 2520-630 Peniche, PortugalDepartament of Pharmacology, Faculty of Veterinary, University of Santiago de Compostela, 27002 Lugo, SpainDepartament of Pharmacology, Faculty of Veterinary, University of Santiago de Compostela, 27002 Lugo, SpainMARE—Marine and Environmental Sciences Centre, Politécnico de Leiria, 2520-630 Peniche, PortugalCell Culture Laboratory, Postgraduate Programme in Biotechnology, University of Vale do Taquari-Univates, Lajeado RS 95914-014, BrazilCell Culture Laboratory, Postgraduate Programme in Biotechnology, University of Vale do Taquari-Univates, Lajeado RS 95914-014, BrazilMARE—Marine and Environmental Sciences Centre, Politécnico de Leiria, 2520-630 Peniche, PortugalDepartament of Pharmacology, Faculty of Veterinary, University of Santiago de Compostela, 27002 Lugo, SpainCenter for Neuroscience and Cell Biology (CNC), University of Coimbra, 3004-517 Coimbra, PortugalDepartament of Pharmacology, Faculty of Veterinary, University of Santiago de Compostela, 27002 Lugo, SpainMARE—Marine and Environmental Sciences Centre, ESTM, Politécnico de Leiria, 2520-614 Peniche, PortugalMarine natural products have exhibited uncommon chemical structures with relevant antitumor properties highlighting their potential to inspire the development of new anticancer agents. The goal of this work was to study the antitumor activities of the brominated diterpene sphaerodactylomelol, a rare example of the dactylomelane family. Cytotoxicity (10–100 µM; 24 h) was evaluated on tumor cells (A549, CACO-2, HCT-15, MCF-7, NCI-H226, PC-3, SH-SY5Y, SK-ML-28) and the effects estimated by MTT assay. Hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) levels and apoptosis biomarkers (membrane translocation of phosphatidylserine, depolarization of mitochondrial membrane potential, Caspase-9 activity, and DNA condensation and/or fragmentation) were studied in the breast adenocarcinoma cellular model (MCF-7) and its genotoxicity on mouse fibroblasts (L929). Sphaerodactylomelol displayed an IC<sub>50</sub> range between 33.04 and 89.41 µM without selective activity for a specific tumor tissue. The cells’ viability decrease was accompanied by an increase on H<sub>2</sub>O<sub>2</sub> production, a depolarization of mitochondrial membrane potential and an increase of Caspase-9 activity and DNA fragmentation. However, the DNA damage studies in L929 non-malignant cell line suggested that this compound is not genotoxic for normal fibroblasts. Overall, the results suggest that the cytotoxicity of sphaerodactylomelol seems to be mediated by an increase of H<sub>2</sub>O<sub>2</sub> levels and downstream apoptosis.https://www.mdpi.com/1420-3049/26/5/1374breast cancerred algaeoxidative stressmarine natural productsapoptosisDNA damage |
| spellingShingle | Celso Alves Joana Silva Susete Pinteus Eva Alonso Rebeca Alvariño Adriana Duarte Diorge Marmitt Márcia Inês Goettert Helena Gaspar Amparo Alfonso Maria C. Alpoim Luis M. Botana Rui Pedrosa Cytotoxic Mechanism of Sphaerodactylomelol, an Uncommon Bromoditerpene Isolated from <i>Sphaerococcus coronopifolius</i> Molecules breast cancer red algae oxidative stress marine natural products apoptosis DNA damage |
| title | Cytotoxic Mechanism of Sphaerodactylomelol, an Uncommon Bromoditerpene Isolated from <i>Sphaerococcus coronopifolius</i> |
| title_full | Cytotoxic Mechanism of Sphaerodactylomelol, an Uncommon Bromoditerpene Isolated from <i>Sphaerococcus coronopifolius</i> |
| title_fullStr | Cytotoxic Mechanism of Sphaerodactylomelol, an Uncommon Bromoditerpene Isolated from <i>Sphaerococcus coronopifolius</i> |
| title_full_unstemmed | Cytotoxic Mechanism of Sphaerodactylomelol, an Uncommon Bromoditerpene Isolated from <i>Sphaerococcus coronopifolius</i> |
| title_short | Cytotoxic Mechanism of Sphaerodactylomelol, an Uncommon Bromoditerpene Isolated from <i>Sphaerococcus coronopifolius</i> |
| title_sort | cytotoxic mechanism of sphaerodactylomelol an uncommon bromoditerpene isolated from i sphaerococcus coronopifolius i |
| topic | breast cancer red algae oxidative stress marine natural products apoptosis DNA damage |
| url | https://www.mdpi.com/1420-3049/26/5/1374 |
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