Anticancer Activity of Neosetophomone-B, a Fungal Secondary Metabolite, Against Hematological Malignancies

Abstract

Anticancer Activity of Neosetophomone-B, a Fungal Secondary Metabolite, Against Hematological Malignancies downregulation, and p21 and p27 upregulation were observed in NSP-B-treated leukemia, lymphoma, and myeloma cells. The activation of the JNK pathway was triggered by NSP-B. Gene expression profiling was used to compare NSP-B-treated and untreated cells, and genes that exhibit significant differences in their expression (DEGs) were discovered. BUB1B had the highest connection score among cancer genes, and its downregulation in the treated cell line was particularly intriguing. The Cancer Genome Atlas (TCGA) data revealed that BUB1B was overexpressed in nearly all cancers compared to the normal tissue, and this expression level was associated with a poor prognosis. Similarly, BUB1B strongly correlated with FOXM1 across all TCGA cancer types. This was further confirmed using western blotting and gene-silencing techniques. In addition to causing apoptosis, NSP-B also triggered autophagy. NSP-B was also shown to enhance the anti-cancer effects of both thiostrepton, a direct FOXM1 protein inhibitor, and bortezomib, a proteasome inhibitor, in hematological malignant cells. Benefiting from the multidimensional targeting and effective anti-neoplastic activity in vitro, NSP-B appears to be a promising drug candidate for the treatment of hematological malignancies that yield a grim prognosis and are in dire need of effective therapeutic advances. Furthermore, the findings of the present study provide a rational framework for preclinical efficacy studies that may provide scientific evidence and translational relevance for moving NSP-B and related combinatorial strategies into clinical trials for hematological malignancies.