Cancer is one of the leading causes of death worldwide, accounting for nearly 10 million deaths in 2020. Current treatment methods include
hormone therapy, γ-radiation,
immunotherapy, and
chemotherapy. Although
chemotherapy is the most effective treatment, there are major obstacles posed by resistance mechanisms of
cancer cells and side-effects of the drugs, thus the search for novel anti-
cancer compounds, especially from natural sources, is crucial for
cancer pharmaceutics research. One natural source worthy of investigation is fungal species. In this study, the cytotoxicity of 5 metabolic compounds isolated from filamentous fungus Aspergillus Carneus.
Arugosin C,
Averufin,
Averufanin, Nidurifin and
Versicolorin C were analyzed using NCI-SRB assay on 10 different cell lines of
breast cancer,
ovarian cancer,
glioblastoma and non-tumorigenic cell lines.
Averufanin showed highest cytotoxicity with lowest IC50 concentrations especially on
breast cancer cells. Therefore,
Averufanin was further investigated to enlighten cell death and molecular mechanisms of action involved. Cell cycle analysis showed increase in SubG1 phase suggesting apoptosis induction which was further confirmed by
Annexin V and
Caspase 3/7 Assays. H2A.X staining revealed accumulation of DNA damage in cells treated with
Averufanin and finally western blot analysis validated DNA damage response and downstream effects of
Averufanin treatment in various signaling pathways. Consequently, this study shows that
Averufanin compound induces cell cycle arrest and cell death via apoptosis through causing DNA damage and can be contemplated and further explored as a new therapeutic strategy in
breast cancer.