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    Marine‑derived Fungi Extracts Enhance the Cytotoxic Activity of Doxorubicin in Nonsmall Cell Lung Cancer Cells A459

    Bruno Castro‑Carvalho1,2, Alice A. Ramos1,2, Maria Prata‑Sena1,2, Fernanda Malhão1,2, Márcia Moreira1, Daniela Gargiulo1,3, Tida Dethoup4, Suradet Buttachon1,5, Anake Kijjoa1,5, Eduardo Rocha1,2★★ Corresponding author

    1. 1Interdisciplinary Center for Marine and Environmental Research, University of Porto, 4450‑208 Matosinhos, PORTUGAL.
    2. 2Departments of Microscopy, Institute of Biomedical Sciences Abel Salazar, University of Porto, 4050‑313 Porto, PORTUGAL.
    3. 3University Center of Belo Horizonte, University of Minas Gerais, Belo Horizonte, BRAZIL.
    4. 4Department of Plant Pathology, Faculty of Agriculture, Kasetsart University, Bangkok, THAILAND.
    5. 5Departments of Chemistry, Institute of Biomedical Sciences Abel Salazar, University of Porto, 4050‑313 Porto, PORTUGAL.

    CORRESPONDENCE

    Eduardo Rocha

    Interdisciplinary Center for Marine and Environmental Research, University of Porto, 4450‑208 Matosinhos, PORTUGAL.

    erocha@icbas.up.pt

    Volume 9, Issue 5S · pp. s92–s98 · PUBLISHED · DOI: 10.4103/pr.pr_57_17

    View on Pharmacogn. Res. original site ↗

    ABSTRACT

    Background:Drug resistance is a major concern in the current chemotherapeutic approaches and the combination with natural compounds may enhance the cytotoxic effects of the anticancer drugs. Therefore, this study evaluated the cytotoxicity of crude ethyl extracts of six marine‑derived fungi – Neosartorya tsunodaeKUFC 9213 (E1), Neosartorya laciniosa KUFC 7896 (E2), Neosartorya fischeriKUFC 6344 (E3), Aspergillus similanensis KUFA 0013 (E4),Neosartorya paulistensis KUFC 7894 (E5), and Talaromyces trachyspermum KUFC 0021 (E6) – when combined with doxorubicin (Dox), in seven human cancer cell lines. Materials and Methods: The antiproliferative activity was primarily assessed by the 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide assay. Results: Two extracts, E1 and E2, demonstrated a significant enhancement of Dox’s cytotoxicity in nonsmall cell lung cancer A549 cells. Accumulation of Dox in the nuclei increased when A549 cells were treated in combination with extracts E1 and E2, with induction of cell death observed by the nuclear condensation assay. The combination of E2 with Dox increased the DNA damage as detected by the comet assay. Ultrastructural observations by transmission electron microscopy suggest an autophagic cell death due to an increase of autophagic vesicles, namely with the combination of Dox with E1 and E2. Conclusion: These findings led to the conclusion that the fungal extracts E1 and E2 potentiate the anticancer action of Dox, through nuclear accumulation of Dox with induction of cell death mainly by cytotoxic autophagy.

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      Castro‑Carvalho, B., Ramos, A. A., Prata‑Sena, M., Malhão, F., Moreira, M., Gargiulo, D., Dethoup, T., Buttachon, S., Kijjoa, A., & Rocha, E. (). Marine‑derived Fungi Extracts Enhance the Cytotoxic Activity of Doxorubicin in Nonsmall Cell Lung Cancer Cells A459. Pharmacognosy Research, 9(5S), s92–s98. https://doi.org/10.4103/pr.pr_57_17