Metabolomic profiling and anticancer effects of Red Sea sponges Liosina granularis and Callyspongia crassa on prostate and ovarian cancer cells

Abstract Marine sponges are rich sources of bioactive secondary metabolites with potential relevance to anticancer drug discovery. This study investigated the metabolomic profiles and preliminary anticancer activity of methanolic extracts from two Red Sea sponge species, Liosina granularis (LGE) and Callyspongia crassa (CCE), using prostate (PC3) and ovarian (SKOV-3) cancer cell models. LC-MS/MS analysis annotated 44 metabolites, including alkaloids, long-chain amides, fatty acids, polyketides, and terpenoids. Cytotoxicity was assessed using the SRB assay, in which LGE showed marked activity against SKOV-3 cells, with an IC₅₀ of 0.5 µg/mL. Flow cytometry revealed treatment-associated changes in Annexin V/PI staining patterns and cell cycle distribution. LGE was mainly associated with G2-phase accumulation, whereas CCE was associated with an increased S-phase population. Acridine orange staining indicated increased acidic vesicular organelle accumulation, particularly in LGE-treated cells. Molecular docking was used as an exploratory computational approach to evaluate predicted interactions between selected annotated metabolites and PI3Kα, EGFR, and PARP, and to prioritize candidates for future validation. Overall, the findings suggest that LGE and CCE possess antiproliferative activity in the tested cancer cell models and induce measurable phenotypic changes. However, further studies using isolated metabolites, non-cancer comparative models, and molecular pathway validation are required to confirm selectivity, target engagement, and underlying mechanisms.