Bioactivity screening of antarctic sponges reveals anticancer activity and potential cell death via ferroptosis by mycalols

Sponges are known to produce a series of compounds with bioactivities useful for human health. This study was conducted on four sponges collected in the framework of the XXXIV Italian National Antarctic Research Program (PNRA) in November-December 2018, i.e., Mycale (Oxymycale) acerata, Haliclona (R...

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Bibliographic Details
Published in:Marine Drugs
Main Authors: Riccio G., Nuzzo G., Zazo G., Coppola D., Senese G., Romano L., Costantini M., Ruocco N., Bertolino M., Fontana A., Ianora A., Verde C., Giordano D., Lauritano C.
Other Authors: Riccio, G., Nuzzo, G., Zazo, G., Coppola, D., Senese, G., Romano, L., Costantini, M., Ruocco, N., Bertolino, M., Fontana, A., Ianora, A., Verde, C., Giordano, D., Lauritano, C.
Format: Article in Journal/Newspaper
Language:English
Published: MDPI 2021
Subjects:
Antarctica
Drug discovery
Marine biotechnology
Mycalol
Sponge
Animal
Antarctic Region
Antineoplastic Agent
Aquatic Organism
Cell Line
Tumor
Fatty Alcohol
Hep G2 Cell
Human
Phytotherapy
Porifera
Antarctic
Antarc*
Italian National Antarctic Research Program
National Antarctic Research Program
Online Access:http://hdl.handle.net/11567/1078598
https://doi.org/10.3390/MD19080459
Description
Summary:Sponges are known to produce a series of compounds with bioactivities useful for human health. This study was conducted on four sponges collected in the framework of the XXXIV Italian National Antarctic Research Program (PNRA) in November-December 2018, i.e., Mycale (Oxymycale) acerata, Haliclona (Rhizoniera) dancoi, Hemimycale topsenti, and Hemigellius pilosus. Sponge extracts were fractioned and tested against hepatocellular carcinoma (HepG2), lung carcinoma (A549), and melanoma cells (A2058), in order to screen for antiproliferative or cytotoxic activity. Two different chemical classes of compounds, belonging to mycalols and suberitenones, were identified in the active fractions. Mycalols were the most active compounds, and their mechanism of action was also investigated at the gene and protein levels in HepG2 cells. Of the differentially expressed genes, ULK1 and GALNT5 were the most down-regulated genes, while MAPK8 was one of the most up-regulated genes. These genes were previously associated with ferroptosis, a programmed cell death triggered by iron-dependent lipid peroxidation, confirmed at the protein level by the down-regulation of GPX4, a key regulator of ferroptosis, and the up-regulation of NCOA4, involved in iron homeostasis. These data suggest, for the first time, that mycalols act by triggering ferroptosis in HepG2 cells.

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