Anticancer activity of Neosetophomone B by targeting AKT/SKP2/MTH1 axis in leukemic cells

Neosetophomone B (NSP-B), a meroterpenoid fungal secondary metabolite, was investigated for its anticancer potential in leukemic cell lines (K562 and U937). NSP-B treatment of leukemic cells suppressed cell viability by triggering apoptotic cell death. Apoptosis induced by NSP-B is triggered by mitochondrial signaling and caspase activation. Additionally, NSP-B treatment of leukemic cells causes AKT's inactivation accompanied by downregulation of SKP2 oncogene and MTH1 with a concomitant increase of p21Cip1and p27Kip1. Furthermore, NSP-B causes suppression of antiapoptotic proteins, including cIAP1, cIAP2, XIAP, survivin and BCl-XL. Overall, NSP-B reduces cell viability by mitochondrial and caspase-dependent apoptosis. The inhibition of AKT and SKP2 axis could be a promising therapeutic target for leukemia treatment.(c) 2022 Published by Elsevier Inc.

Automated summary

The meroterpenoid fungal secondary metabolite Neosetophomone B (NSP-B) has been found to possess anticancer potential in leukemic cell lines. NSP-B treatment induces apoptosis through mitochondrial signaling and caspase activation, leading to a reduction in cell viability. Moreover, NSP-B treatment results in the inactivation of AKT and downregulation of SKP2 oncogene and MTH1, along with an increase in p21Cip1 and p27Kip1. Additionally, NSP-B suppresses the expression of antiapoptotic proteins such as cIAP1, cIAP2, XIAP, survivin, and BCl-XL. Overall, NSP-B reduces cell viability through mitochondrial and caspase-dependent apoptosis, and targeting the AKT and SKP2 axis may offer a promising therapeutic approach for leukemia.