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

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    1-s2.0-S0006291X22002601-main.pdf (1.139Mb)
    Date
    2022-04-23
    Author
    Kuttikrishnan, Shilpa
    Bhat, Ajaz A.
    Mateo, Jericha M.
    Ahmad, Fareed
    Alali, Feras Q.
    El-Elimat, Tamam
    Oberlies, Nicholas H.
    Pearce, Cedric J.
    Uddin, Shahab
    ...show more authors ...show less authors
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    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.
    URI
    https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85126115788&origin=inward
    DOI/handle
    http://dx.doi.org/10.1016/j.bbrc.2022.02.071
    http://hdl.handle.net/10576/42517
    Collections
    • Laboratory Animal Research Center (Research) [‎129‎ items ]
    • Pharmacy Research [‎1389‎ items ]
    • QU Health Research [‎110‎ items ]

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