Oxidative stress-induced DNA damage and apoptosis in multiple cancer cell lines: novel anticancer properties of marine <i>Aspergillus oryzae</i> NGM91 extract

This study explored the metabolites and bioactive potential of the ethyl acetate extract from a marine-derived fungal strain, <i>Aspergillus oryzae</i> NGM91, isolated from Red Sea sediments. Chemical profiling through FT-IR, GC-MS, and HPLC analysis revealed a complex composition dominated by benzyl benzoate (79.99%) and rosmarinic acid (162.15 μg ml^-1) as major constituents. The fungal extract exhibited potent free radical scavenging activity (DPPH IC₅₀ = 17.26; ABTS IC₅₀ = 27.91 μg ml^-1), with high total antioxidant capacity (476.57 μg per mg AAE) and ferric reducing power (302.62 μg per mg AAE). It demonstrated selective COX inhibition (COX-1 IC₅₀: 20.66 μg ml^-1; COX-2 IC₅₀: 36.32 μg ml^-1). Cytotoxic screening showed significant activity against PC3 cells (IC₅₀: 70.47 μg ml^-1), PANC-1 (IC₅₀: 90.42 μg ml^-1), HepG2 (IC₅₀: 100.36 μg ml^-1), and Caco-2 cells (IC₅₀: 104.69 μg ml^-1), while exhibiting lower cytotoxicity towards normal Wi-38 fibroblasts (IC₅₀: 230.31 μg ml^-1). In PC3 cells, the extract induced oxidative stress markers (MDA: 13.63 μmol mg^-1; NO: 66.13 μmole per mg), modulated antioxidant enzyme activities, upregulated antioxidant genes (CAT: 1195%, SOD: 788%, GPx: 473%, GST: 251%), increased DNA damage (205.1%), activated apoptotic pathways <i>via</i> BCL-2 downregulation and BAX/P53/Caspase-3 upregulation, and induced G1 phase arrest (72.97%). These findings demonstrate <i>A. oryzae</i> NGM91's therapeutic potential through oxidative stress-mediated DNA damage and apoptotic cell death induction in PC3 cancerous cells.