Abstract

Our previous study revealed 17 stably re-culturable marine fungi strains isolated from the South Coast of Jember, East Java, Indonesia. This research was conducted to determine the fungi’s cancer chemoprevention activity and the potential candidate’s metabolite profile. First, their secondary metabolites were extracted using ethyl acetate, and then the extracts were evaluated by their cytotoxicity and selectivity on several cancer cell lines (T47D breast cancer, HeLa cervical cancer, and WiDr colon cancer) and normal cell lines (Vero) using the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The selective cytotoxic marine fungi were then analyzed for cell cycle and apoptosis induction using flow cytometry and their metabolite profile using untargeted ultra-high performance liquid chromatography—high-resolution mass spectrometry (UHPLC-HRMS). Among the extracted fungi, the Aspergillus stromatoides strain SaH 1 demonstrated potential as a source of cancer chemopreventive compounds on T47D breast cancer cells based on cytotoxicity and selectivity assays, warranting further bioactivity-guided isolation and characterization studies. The cell cycle and apoptosis analysis demonstrated that it induced G0-G1 and G2/M cell cycle arrest and induced apoptosis, not necrosis, suggesting that this strain could be developed as a cancer chemoprevention agent. The metabolite profile of A. stromatoides strain SaH 1 using UHPLC-HRMS analysis revealed 606 molecular features, 76% without reported matches, indicating potential novel metabolites that require further structural confirmation. Among them, two compounds—flavoglaucin and 7β-hydroxy-DHEA—have been reported in Aspergillus sp. with documented anticancer properties; these metabolites may have contributed to, but do not solely account for, the anticancer activity observed in SaH 1. This study highlights A. stromatoides strain SaH 1 as a preliminary candidate for breast cancer chemoprevention, with further isolation and in vivo validation needed to confirm its potential.

Key words: culturable marine fungi; A. stromatoides strain SaH 1; flavoglaucin; 7β-hydroxy-DHEA; anticancer