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10.1016_j.bbrc.2022.02.071.pdf (1.14 MB)

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

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submitted on 2023-12-06, 11:50 and posted on 2023-12-07, 07:57 authored by Shilpa Kuttikrishnan, Ajaz A. Bhat, Jericha M. Mateo, Fareed Ahmad, Feras Q. Alali, Tamam El-Elimat, Nicholas H. Oberlies, Cedric J. Pearce, Shahab Uddin

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.

Other Information

Published in: Biochemical and Biophysical Research Communications
License: http://creativecommons.org/licenses/by/4.0/
See article on publisher's website: https://dx.doi.org/10.1016/j.bbrc.2022.02.071

Funding

Open Access funding provided by the Qatar National Library.

History

Language

  • English

Publisher

Elsevier

Publication Year

  • 2022

License statement

This Item is licensed under the Creative Commons Attribution 4.0 International License.

Institution affiliated with

  • Hamad Medical Corporation
  • Academic Health System - HMC
  • Dermatology Institute - HMC
  • Interim Translational Research Institute - HMC
  • Qatar University
  • Laboratory Animal Research Center - QU
  • Qatar University Health - QU
  • College of Pharmacy - QU HEALTH
  • Biomedical and Pharmaceutical Research Unit - QU HEALTH
  • Sidra Medicine