Exploiting bioactive natural products of marine origin: Evaluation of the meroterpenoid metachromin V as a novel potential therapeutic drug for colorectal cancer
Colorectal cancer (CRC) is the second most common cause of cancer death, leading to almost 1 million deaths per year. Despite constant progress in surgical and therapeutic protocols, the 5-year survival rate of advanced CRC patients remains extremely poor. Colorectal Cancer Stem Cells (CRC-CSCs) are...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-06-01
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| Series: | Biomedicine & Pharmacotherapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332223004675 |
| _version_ | 1797837153737113600 |
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| author | Donatella Lucchetti Francesca Luongo Filomena Colella Enrico Gurreri Giulia Artemi Claudia Desiderio Stefano Serra Felice Giuliante Ruggero De Maria Alessandro Sgambato Alberto Vitali Micol Eleonora Fiori |
| author_facet | Donatella Lucchetti Francesca Luongo Filomena Colella Enrico Gurreri Giulia Artemi Claudia Desiderio Stefano Serra Felice Giuliante Ruggero De Maria Alessandro Sgambato Alberto Vitali Micol Eleonora Fiori |
| author_sort | Donatella Lucchetti |
| collection | DOAJ |
| description | Colorectal cancer (CRC) is the second most common cause of cancer death, leading to almost 1 million deaths per year. Despite constant progress in surgical and therapeutic protocols, the 5-year survival rate of advanced CRC patients remains extremely poor. Colorectal Cancer Stem Cells (CRC-CSCs) are endowed with unique stemness-related properties responsible for resistance, relapse and metastasis. The development of novel therapeutics able to tackle CSCs while avoiding undesired toxicity is a major need for cancer treatment. Natural products are a large reservoir of unexplored compounds with possible anticancer bioactivity, sustainability, and safety. The family of meroterpenoids derived from sponges share interesting bioactive properties. Bioassay-guided fractionation of a meroterpenoids extract led to the isolation of three compounds, all cytotoxic against several cancer cell lines: Metachromins U, V and W. In this study, we evaluated the anticancer potential of the most active one, Metachromins V (MV), on patient-derived CRC-CSCs. MV strongly impairs CSCs-viability regardless their mutational background and the cytotoxic effect is maintained on therapy-resistant metastatic CSCs. MV affects cell cycle progression, inducing a block in G2 phase in all the cell lines tested and more pronouncedly in CRC-CSCs. Moreover, MV triggers an important reorganization of the cytoskeleton and a strong reduction of Rho GTPases expression, impairing CRC-CSCs motility and invasion ability. By Proteomic analysis identified a potential molecular target of MV: CCAR1, that regulates apoptosis under chemotherapy treatments and affect β-catenin pathway. Further studies will be needed to confirm and validate these data in in vivo experimental models |
| first_indexed | 2024-04-09T15:20:11Z |
| format | Article |
| id | doaj.art-3ab2e46a1956458eb8e1300c3a9ad3d6 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-04-09T15:20:11Z |
| publishDate | 2023-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-3ab2e46a1956458eb8e1300c3a9ad3d62023-04-29T14:46:18ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-06-01162114679Exploiting bioactive natural products of marine origin: Evaluation of the meroterpenoid metachromin V as a novel potential therapeutic drug for colorectal cancerDonatella Lucchetti0Francesca Luongo1Filomena Colella2Enrico Gurreri3Giulia Artemi4Claudia Desiderio5Stefano Serra6Felice Giuliante7Ruggero De Maria8Alessandro Sgambato9Alberto Vitali10Micol Eleonora Fiori11Dipartimento di Medicina e Chirurgia traslazionale - Facoltà di Medicina e Chirurgia, Università Cattolica del Sacro Cuore, Rome, Italy; Fondazione Policlinico Universitario ''A. Gemelli'' - IRCCS, Rome, ItalyFondazione Policlinico Universitario ''A. Gemelli'' - IRCCS, Rome, ItalyDipartimento di Medicina e Chirurgia traslazionale - Facoltà di Medicina e Chirurgia, Università Cattolica del Sacro Cuore, Rome, ItalyFondazione Policlinico Universitario ''A. Gemelli'' - IRCCS, Rome, ItalyDipartimento di Medicina e Chirurgia traslazionale - Facoltà di Medicina e Chirurgia, Università Cattolica del Sacro Cuore, Rome, ItalyIstituto di Scienze e Tecnologie Chimiche''Giulio Natta'' (SCITEC), Consiglio Nazionale delle Ricerche (CNR), Rome, ItalyIstituto di Scienze e Tecnologie Chimiche ''Giulio Natta'' (SCITEC), Consiglio Nazionale delle Ricerche (CNR),. Milano, ItalyDipartimento di Scienze Mediche e Chirurgiche, Chirurgia Generale ed Epato-Biliare, Fondazione Policlinico Universitario “A. Gemelli= - IRCCS, Rome, ItalyDipartimento di Medicina e Chirurgia traslazionale - Facoltà di Medicina e Chirurgia, Università Cattolica del Sacro Cuore, Rome, Italy; Fondazione Policlinico Universitario ''A. Gemelli'' - IRCCS, Rome, ItalyDipartimento di Medicina e Chirurgia traslazionale - Facoltà di Medicina e Chirurgia, Università Cattolica del Sacro Cuore, Rome, Italy; Fondazione Policlinico Universitario ''A. Gemelli'' - IRCCS, Rome, Italy; Corresponding author at: Dipartimento di Medicina e Chirurgia traslazionale - Facoltà di Medicina e Chirurgia, Università Cattolica del Sacro Cuore, Rome, Italy.Istituto di Scienze e Tecnologie Chimiche''Giulio Natta'' (SCITEC), Consiglio Nazionale delle Ricerche (CNR), Rome, ItalyDepartment of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, ItalyColorectal cancer (CRC) is the second most common cause of cancer death, leading to almost 1 million deaths per year. Despite constant progress in surgical and therapeutic protocols, the 5-year survival rate of advanced CRC patients remains extremely poor. Colorectal Cancer Stem Cells (CRC-CSCs) are endowed with unique stemness-related properties responsible for resistance, relapse and metastasis. The development of novel therapeutics able to tackle CSCs while avoiding undesired toxicity is a major need for cancer treatment. Natural products are a large reservoir of unexplored compounds with possible anticancer bioactivity, sustainability, and safety. The family of meroterpenoids derived from sponges share interesting bioactive properties. Bioassay-guided fractionation of a meroterpenoids extract led to the isolation of three compounds, all cytotoxic against several cancer cell lines: Metachromins U, V and W. In this study, we evaluated the anticancer potential of the most active one, Metachromins V (MV), on patient-derived CRC-CSCs. MV strongly impairs CSCs-viability regardless their mutational background and the cytotoxic effect is maintained on therapy-resistant metastatic CSCs. MV affects cell cycle progression, inducing a block in G2 phase in all the cell lines tested and more pronouncedly in CRC-CSCs. Moreover, MV triggers an important reorganization of the cytoskeleton and a strong reduction of Rho GTPases expression, impairing CRC-CSCs motility and invasion ability. By Proteomic analysis identified a potential molecular target of MV: CCAR1, that regulates apoptosis under chemotherapy treatments and affect β-catenin pathway. Further studies will be needed to confirm and validate these data in in vivo experimental modelshttp://www.sciencedirect.com/science/article/pii/S0753332223004675Natural productsTherapeutic drugColorectal cancerCancer stem cells |
| spellingShingle | Donatella Lucchetti Francesca Luongo Filomena Colella Enrico Gurreri Giulia Artemi Claudia Desiderio Stefano Serra Felice Giuliante Ruggero De Maria Alessandro Sgambato Alberto Vitali Micol Eleonora Fiori Exploiting bioactive natural products of marine origin: Evaluation of the meroterpenoid metachromin V as a novel potential therapeutic drug for colorectal cancer Biomedicine & Pharmacotherapy Natural products Therapeutic drug Colorectal cancer Cancer stem cells |
| title | Exploiting bioactive natural products of marine origin: Evaluation of the meroterpenoid metachromin V as a novel potential therapeutic drug for colorectal cancer |
| title_full | Exploiting bioactive natural products of marine origin: Evaluation of the meroterpenoid metachromin V as a novel potential therapeutic drug for colorectal cancer |
| title_fullStr | Exploiting bioactive natural products of marine origin: Evaluation of the meroterpenoid metachromin V as a novel potential therapeutic drug for colorectal cancer |
| title_full_unstemmed | Exploiting bioactive natural products of marine origin: Evaluation of the meroterpenoid metachromin V as a novel potential therapeutic drug for colorectal cancer |
| title_short | Exploiting bioactive natural products of marine origin: Evaluation of the meroterpenoid metachromin V as a novel potential therapeutic drug for colorectal cancer |
| title_sort | exploiting bioactive natural products of marine origin evaluation of the meroterpenoid metachromin v as a novel potential therapeutic drug for colorectal cancer |
| topic | Natural products Therapeutic drug Colorectal cancer Cancer stem cells |
| url | http://www.sciencedirect.com/science/article/pii/S0753332223004675 |
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