Anticancer activity of Neosetophomone B by targeting AKT/SKP2/MTH1 axis in leukemic cells
| Author | Kuttikrishnan, Shilpa |
| Author | Bhat, Ajaz A. |
| Author | Mateo, Jericha M. |
| Author | Ahmad, Fareed |
| Author | Alali, Feras Q. |
| Author | El-Elimat, Tamam |
| Author | Oberlies, Nicholas H. |
| Author | Pearce, Cedric J. |
| Author | Uddin, Shahab |
| Available date | 2023-05-10T03:43:46Z |
| Publication Date | 2022-04-23 |
| Publication Name | Biochemical and Biophysical Research Communications |
| Identifier | http://dx.doi.org/10.1016/j.bbrc.2022.02.071 |
| Citation | Kuttikrishnan S, Bhat AA, Mateo JM, Ahmad F, Alali FQ, El-Elimat T, Oberlies NH, Pearce CJ, Uddin S. Anticancer activity of Neosetophomone B by targeting AKT/SKP2/MTH1 axis in leukemic cells. Biochem Biophys Res Commun. 2022 Apr 23;601:59-64. doi: 10.1016/j.bbrc.2022.02.071. |
| ISSN | 0006291X |
| 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. |
| Sponsor | This work was supported by grant funded by the Medical Research Center (MRC), Hamad Medical Corporation, Doha, Qatar (MRC-01-21-301). The authors thank Qatar National Library for open access support of this article. |
| Language | en |
| Publisher | Elsevier |
| Subject | Apoptosis Fungal secondary metabolites Leukemia Meroterpenoids Natural products Neosetophomone B |
| Type | Article |
| Pagination | 59-64 |
| Volume Number | 601 |
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