LAUSR

The exploration of natural antioxidants for nutraceuticals and pharmaceuticals industries has recently increased. In this scenario, marine microorganisms, represent underestimated sources of bioactive products endowed with beneficial effects on health, that include anti-oxidant, anti-tumor and anti-angiogenic activities. Here, we tested the potential cancer preventive activities of extracts from the marine coastal diatom Skeletonema marinoi Sarno and Zingone (CCMP 2092) on prostate cancer cells, in vitro. Skeletonema marinoi was grown under a sinusoidal light distribution with a midday peak of 150 μmol photons m−2 s−1, and then, once cells reached the exponential phase, shifted to a sinusoidal light distribution with a higher midday peak light intensity of 600 μmol photons m−2 s−1. This high light condition induces in cells the synthesis of antioxidant and protective molecules. Total wet biomass was collected and chemically extracted by methanol solvent. The dried extract was tested as a food supplement on prostate (PC-3), as compared to normal prostate epithelium. Gene expression analysis was performed by qPCR, measuring the variation of 365 different genes involved in the apoptosis and immunogenic cell death pathways. Treatments with Skeletonema marinoi extracts (1-10-100 µg ml-1) resulted in a statistically significant, dose dependent, antiproliferative (inhibition at 70% of cell viability at 100 µg ml-1) and pro-apoptotic effects in PC-3 cells, while sparing normal epithelial prostatic cells. Among the gene panel analysed as key indicators of the PC3 cell fate in terms of signalling pathway prediction, we observed up/down regulation of APAF1, BAD, BAG1, BAG3, BAK1, BAX, BCL2, BCL2L1, BCL2L13, BCL2L2, BCL3, BDNF, BECN1, BFAR, BID, BIK, BIRC2, BIRC3, BIRC6, BNIP1, BOK, BRAF, BRCA1, BRE, CARD17, CARD9, CASP1-2-3-4-5-6-7-10-14, CBX4, CRADD, DEDD, DHCR24, FADD, FAS, FASLG, FASTK. The integrated gene expression analysis revealed necroptosis activation in cells with the up-regulation of the inflammatory mediators such as F2R, F2, IL18-19-A-31RA, SOCS2, SOCS3 genes and the downregulation of the angiogenic factors such as ALOX12, ALOX15B, PIK3CA, PIK3R2, and VEGF genes. One of the main candidates as compounds responsible for such cancer preventive activities is the diatom-xanthophyll photoprotective diatoxanthin, probably in synergy with other molecules. Further metabolomics analysis on the extracts will help in understanding and interpretation of the results. These results demonstrate promising cancer preventive activities of Skeletonema marinoi extracts in PC3 cell lines. This confirms microalgal-derived drugs as potential relevant source of nutraceutical novel food and candidate as potential dietary intervention in cancer prevention approaches. Citation Format: Clementina Sansone, Piscitelli Concetta, Galasso Christian, Smerilli Arianna, Bruno Antonino, Noonan Douglas, Albini Adriana, Brunet Christophe. Skeletonema marinoi (diatom) extracts are endowed with promising cancer preventive properties in prostate cancer cells [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 25.