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Anticancer activity of Neosetophomone B by targeting AKT/SKP2/MTH1 axis in leukemic cells
Shilpa Kuttikrishnan1, Ajaz A Bhat2, Jericha M Mateo3
1Translational Research Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar; College of Pharmacy, QU Health, Qatar University, Doha, Qatar.
Abstract:
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.
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