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

ABSTRACT: 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.

SUBMITTER: Riccio G

PROVIDER: S-EPMC8400861 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Marine sponges host dense, diverse, and species-specific microbial communities around the globe; however, most of the current knowledge is restricted to species from tropical and temperate waters. Only recently, some studies have assessed the microbiome of a few Antarctic sponges; however, contrary to low mid-latitude sponges, the knowledge about temporal (stability) patterns in the bacterial communities of Antarctic sponges is absent. Here, we studied the temporal patterns of bacterial communities in the Antarctic sponges Mycale (Oxymycale) acerata, Isodictya sp., Hymeniacidon torquata, and Tedania (Tedaniopsis) wellsae that were tagged in situ and monitored during three austral summers over a 24-month period. By using amplicon sequencing of the bacterial 16S rRNA gene we found that the microbiome differed between species. In general, bacterial communities were dominated by gammaproteobacterial OTUs; however, M. acerata showed the most distinct pattern, being dominated by a single betaproteobacterial OTU. The analysis at OTU level (defined at 97% sequence similarity) showed a highly stable bacterial community through time, despite the abnormal seawater temperatures (reaching 3°C) and rates of temperature increase of 0.15°C day-1 recorded in austral summer 2017. Sponges were characterized by a small core bacterial community that accounted for a high percentage of the abundance. Overall, no consistent changes in core OTU abundance were recorded for all studied species, confirming a high temporal stability of the microbiome. In addition, predicted functional pathway profiles showed that the most abundant pathways among all sponges belonged mostly to metabolism pathway groups (e.g., amino acid, carbohydrate, energy, and nucleotide). The predicted functional pathway patterns differed among the four sponge species. However, no clear temporal differences were detected supporting what was found in terms of the relatively stable composition of the bacterial communities.

Project description:The microbial biogeochemical processes occurring in marine sediment in Antarctica remain underexplored due to limited access. Further, these polar habitats are unique, as they are being exposed to significant changes in their climate. To explore how microbes drive biogeochemistry in these sediments, we performed a shotgun metagenomic survey of marine surficial sediment (0 to 3 cm of the seafloor) collected from 13 locations in western Antarctica and assembled 16 high-quality metagenome assembled genomes for focused interrogation of the lifestyles of some abundant lineages. We observe an abundance of genes from pathways for the utilization of reduced carbon, sulfur, and nitrogen sources. Although organotrophy is pervasive, nitrification and sulfide oxidation are the dominant lithotrophic pathways and likely fuel carbon fixation via the reverse tricarboxylic acid and Calvin cycles. Oxygen-dependent terminal oxidases are common, and genes for reduction of oxidized nitrogen are sporadically present in our samples. Our results suggest that the underlying benthic communities are well primed for the utilization of settling organic matter, which is consistent with findings from highly productive surface water. Despite the genetic potential for nitrate reduction, the net catabolic pathway in our samples remains aerobic respiration, likely coupled to the oxidation of sulfur and nitrogen imported from the highly productive Antarctic water column above. IMPORTANCE The impacts of climate change in polar regions, like Antarctica, have the potential to alter numerous ecosystems and biogeochemical cycles. Increasing temperature and freshwater runoff from melting ice can have profound impacts on the cycling of organic and inorganic nutrients between the pelagic and benthic ecosystems. Within the benthos, sediment microbial communities play a critical role in carbon mineralization and the cycles of essential nutrients like nitrogen and sulfur. Metagenomic data collected from sediment samples from the continental shelf of western Antarctica help to examine this unique system and document the metagenomic potential for lithotrophic metabolisms and the cycles of both nitrogen and sulfur, which support not only benthic microbes but also life in the pelagic zone.

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

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