Secondary Metabolites from the Culture of the Marine-derived Fungus Paradendryphiella salina PC 362H and Evaluation of the Anticancer Activity of Its Metabolite Hyalodendrin
Open Access
- 2 April 2020
- journal article
- research article
- Published by MDPI AG in Marine Drugs
- Vol. 18 (4), 191
- https://doi.org/10.3390/md18040191
Abstract
High-throughput screening assays have been designed to identify compounds capable of inhibiting phenotypes involved in cancer aggressiveness. However, most studies used commercially available chemical libraries. This prompted us to explore natural products isolated from marine-derived fungi as a new source of molecules. In this study, we established a chemical library from 99 strains corresponding to 45 molecular operational taxonomic units and evaluated their anticancer activity against the MCF7 epithelial cancer cell line and its invasive stem cell-like MCF7-Sh-WISP2 counterpart. We identified the marine fungal Paradendryphiella salina PC 362H strain, isolated from the brown alga Pelvetia caniculata (PC), as one of the most promising fungi which produce active compounds. Further chemical and biological characterizations of the culture of the Paradendryphiella salina PC 362H strain identified (-)-hyalodendrin as the active secondary metabolite responsible for the cytotoxic activity of the crude extract. The antitumor activity of (-)-hyalodendrin was not only limited to the MCF7 cell lines, but also prominent on cancer cells with invasive phenotypes including colorectal cancer cells resistant to chemotherapy. Further investigations showed that treatment of MCF7-Sh-WISP2 cells with (-)-hyalodendrin induced changes in the phosphorylation status of p53 and altered expression of HSP60, HSP70 and PRAS40 proteins. Altogether, our study reveals that this uninvestigated marine fungal crude extract possesses a strong therapeutic potential against tumor cells with aggressive phenotypes and confirms that members of the epidithiodioxopiperazines are interesting fungal toxins with anticancer activities.Funding Information
- Agence Nationale de la Recherche (ANR-LABX-011, ANR-11-EQPX-0008)
This publication has 65 references indexed in Scilit:
- Hyperglycaemia and oxidative stress upregulate HSP60 & HSP70 expression in HeLa cellsSpringerPlus, 2013
- Plant cytoplasmic GAPDH: redox post-translational modifications and moonlighting propertiesFrontiers in Plant Science, 2013
- Glutathionylation in the Photosynthetic Model Organism Chlamydomonas reinhardtii: A Proteomic SurveyMolecular & Cellular Proteomics, 2012
- Clonal evolution in cancerNature, 2012
- p53, Oxidative Stress, and AgingAntioxidants and Redox Signaling, 2011
- Genotypic and Histological Evolution of Lung Cancers Acquiring Resistance to EGFR InhibitorsScience Translational Medicine, 2011
- Role of p53 Serine 46 in p53 Target Gene RegulationPLOS ONE, 2011
- Role of WISP-2/CCN5 in the Maintenance of a Differentiated and Noninvasive Phenotype in Human Breast Cancer CellsMolecular and Cellular Biology, 2008
- Breast cancer: origins and evolutionJCI Insight, 2007
- Caspase-3 Is Required for DNA Fragmentation and Morphological Changes Associated with ApoptosisOnline Journal of Public Health Informatics, 1998