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Cytotoxic and Antiproliferative Effects of Preussin, a Hydroxypyrrolidine Derivative from the Marine Sponge-Associated Fungus Aspergillus candidus KUFA 0062, in a Panel of Breast Cancer Cell Lines and Using 2D and 3D Cultures

1
Institute of Biomedical Sciences Abel Salazar (ICBAS), Universidade do Porto (U.Porto), Rua de Jorge Viterbo Ferreira n 228, 4050-313 Porto, Portugal
2
Interdisciplinary Center for Marine and Environmental Research (CIIMAR), Universidade do Porto (U.Porto), Avenida General Norton de Matos s/n, 4450-208 Matosinhos, Portugal
3
Department of Plant Pathology, Faculty of Agriculture, Kasetsart University, Bangkok 10240, Thailand
*
Author to whom correspondence should be addressed.
Mar. Drugs 2019, 17(8), 448; https://doi.org/10.3390/md17080448
Received: 16 July 2019 / Revised: 26 July 2019 / Accepted: 27 July 2019 / Published: 30 July 2019
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Abstract

Preussin, a hydroxyl pyrrolidine derivative isolated from the marine sponge-associated fungus Aspergillus candidus KUFA 0062, displayed anticancer effects in some cancer cell lines, including MCF7. Preussin was investigated for its cytotoxic and antiproliferative effects in breast cancer cell lines (MCF7, SKBR3, and MDA-MB-231), representatives of major breast cancers subtypes, and in a non-tumor cell line (MCF12A). Preussin was first tested in 2D (monolayer), and then in 3D (multicellular aggregates), cultures, using a multi-endpoint approach for cytotoxicity (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), resazurin and lactate dehydrogenase (LDH)) and proliferative (5-bromo-2′-deoxyuridine (BrdU)) assays, as well as the analysis of cell morphology by optical/electron microscopy and immunocytochemistry for caspase-3 and ki67. Preussin affected cell viability and proliferation in 2D and 3D cultures in all cell lines tested. The results in the 3D culture showed the same tendency as in the 2D culture, however, cells in the 3D culture were less responsive. The effects were observed at different concentrations of preussin, depending on the cell line and assay method. Morphological study of preussin-exposed cells revealed cell death, which was confirmed by caspase-3 immunostaining. In view of the data, we recommend a multi-endpoint approach, including histological evaluation, in future assays with the tested 3D models. Our data showed cytotoxic and antiproliferative activities of preussin in breast cancer cell lines in 2D and 3D cultures, warranting further studies for its anticancer potential. View Full-Text
Keywords: 3D cell culture; antiproliferative activity; breast cancer; cytotoxic activity; preussin 3D cell culture; antiproliferative activity; breast cancer; cytotoxic activity; preussin
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Malhão, F.; Ramos, A.A.; Buttachon, S.; Dethoup, T.; Kijjoa, A.; Rocha, E. Cytotoxic and Antiproliferative Effects of Preussin, a Hydroxypyrrolidine Derivative from the Marine Sponge-Associated Fungus Aspergillus candidus KUFA 0062, in a Panel of Breast Cancer Cell Lines and Using 2D and 3D Cultures. Mar. Drugs 2019, 17, 448.

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