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

<p>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 triggere...

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Main Author: Shilpa Kuttikrishnan (3520079) (author)
Other Authors: Ajaz A. Bhat (12984701) (author), Jericha M. Mateo (17563293) (author), Fareed Ahmad (134672) (author), Feras Q. Alali (2691907) (author), Tamam El-Elimat (694398) (author), Nicholas H. Oberlies (326437) (author), Cedric J. Pearce (1364220) (author), Shahab Uddin (154400) (author)
Published: 2022
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Summary:<p>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.</p><h2>Other Information</h2> <p> Published in: Biochemical and Biophysical Research Communications<br> License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1016/j.bbrc.2022.02.071" target="_blank">https://dx.doi.org/10.1016/j.bbrc.2022.02.071</a></p>