Bioactivity Screening of Antarctic Sponges Reveals Anticancer Activity and Potential Cell Death via Ferroptosis by Mycalols

• Published in: Marine Drugs
• Main Authors: Gennaro Riccio, Genoveffa Nuzzo, Gianluca Zazo, Daniela Coppola, Giuseppina Senese, Lucia Romano, Maria Costantini, Nadia Ruocco, Marco Bertolino, Angelo Fontana, Adrianna Ianora, Cinzia Verde, Daniela Giordano, Chiara Lauritano
• Format: Text
• Language: English
• Published: Multidisciplinary Digital Publishing Institute 2021
• Subjects: Antarctica; sponges; drug discovery; mycalols; marine biotechnology; Antarctic; Antarc*; Italian National Antarctic Research Program; National Antarctic Research Program
• Online Access: https://doi.org/10.3390/md19080459

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.