The apoptotic and anti-proliferative effects of Neosetophomone B in T-cell acute lymphoblastic leukaemia via PI3K/AKT/mTOR pathway inhibition

Sep 21, 2026

The phosphatidylinositol 3-kinase/Protein Kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signalling pathway is pivotal in various cancers, including T-cell acute lymphoblastic leukaemia (T-ALL), a particularly aggressive type of leukaemia. This study investigates the effects of Neosetophomone B (NSP-B) on T-ALL cell lines, focusing on anti-cancer mechanisms and therapeutic potential. NSP-B inhibits proliferation by inducing G0/G1 arrest and caspase-dependent apoptosis, and dephosphorylates and inactivates PI3K/AKT/mTOR. Docking indicates strong binding of NSP-B to AKT.

LanguageEnglish

CategoryResearch & Report

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Pages13

Reading Time33 min

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Abstract

Introduction

DOI: 10.1111/cpr.13773 O R IG INA L ARTI CLE The apoptotic and anti-proliferative effects of Neosetophomone B in T-cell acute lymphoblastic leukaemia via PI3K/AKT/mTOR pathway inhibition Shilpa Kuttikrishnan 1,2 | Abdul W. Ansari 1,3 | Muhammad Suleman 4 | Fareed Ahmad 1,3 | Kirti S. Prabhu 1 | Tamam El-Elimat 5 | Feras Q. Alali 2 | Ammira S. Al Shabeeb Akil 6 | Ajaz A. Bhat 6 | Maysaloun Merhi 7 | Said Dermime 7,8 | Martin Steinhoff 1,3,9,10,11,12,13 | Shahab Uddin 1,3,4 1Translational Research Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar 2College of Pharmacy, QU Health, Qatar University, Doha, Qatar 3Dermatology Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar 4Laboratory of Animal Research Center, Qatar University, Doha, Qatar 5Department of Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Qatar 6Department of Human Genetics-Precision Medicine in Diabetes, Obesity and Cancer Program, Sidra Medicine, Doha, Qatar 7Translational Cancer Research Facility, National Center for Cancer Care and Research, Hamad Medical Corporation, Doha, Qatar 8College of Health Sciences, Qatar University, Doha, Qatar 9Department of Dermatology & Venereology, Hamad Medical Corporation, Doha, Qatar 10Department of Medicine, Weill Cornell Medicine-Qatar, Doha, Qatar 11College of Medicine, Qatar University, Doha, Qatar 12College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar 13Department of Medicine, Weill Cornell Medicine, New York, New York, USA Correspondence Shahab Uddin, Translational Research Institute, Academic Health System, Hamad Medical Corporation, PO Box 3050, Doha, Qatar. Email: [skhan34@hamad.qa](skhan34@hamad.qa) Funding information Hamad Medical Corporation, Grant/Award Number: MRC-01-21-301 Abstract The phosphatidylinositol 3-kinase/Protein Kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signalling pathway is pivotal in various cancers, including T-cell acute lymphoblastic leukaemia (T-ALL), a particularly aggressive type of leukaemia. This study investigates the effects of Neosetophomone B (NSP-B), a meroterpenoid fungal metabolite, on T-ALL cell lines, focusing on its anti-cancer mechanisms and therapeutic potential. NSP-B significantly inhibited the proliferation of T-ALL cells by inducing G0/G1 cell cycle arrest and promoting caspase-dependent apoptosis. Additionally, NSP-B led to the dephosphorylation and subsequent inactivation of the PI3K/AKT/mTOR signalling pathway, a critical pathway in cell survival and growth. Molecular docking studies revealed a strong binding affinity of NSP-B to the active site of AKT, primarily involving key residues crucial for its activity. Interestingly, | Shilpa Kuttikrishnan, Abdul W. Ansari, and Muhammad Suleman share first authorship. | | --- | | This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
© 2024 The Author(s) . Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd. | Cell Prolif. 2025;58:e13773 . [https://doi.org/10.1111/cpr.13773](https://doi.org/10.1111/cpr.13773) [onlinelibrary.wiley.com/journal/13652184](onlinelibrary.wiley.com/journal/13652184) 1 of 13 NSP-B treatment also induced apoptosis and significantly reduced proliferation in phytohemagglutinin-activated primary human CD3+ T cells, accompanied by a G0/G1 cell cycle arrest. Importantly, NSP-B did not affect normal primary T cells, indicating a degree of selectivity in its action, targeting only T-ALL cells and activated T cells. In conclusion, our findings highlight the potential of NSP-B as a novel therapeutic agent for T-ALL, specifically targeting the aberrantly activated PI3K/AKT/ mTOR pathway and being selective in actio

FAQs

What is the main pathway targeted by Neosetophomone B (NSP-B) in T-ALL?

NSP-B targets the PI3K/AKT/mTOR signalling pathway by causing dephosphorylation and inactivation, reducing survival and growth signals in T-ALL cells.

How does NSP-B inhibit T-ALL cell proliferation?

NSP-B inhibits proliferation by inducing G0/G1 cell cycle arrest and by promoting caspase-dependent apoptosis.

Does NSP-B show selectivity toward cancerous versus normal T cells?

NSP-B does not affect normal primary T cells, indicating selectivity for T-ALL cells and activated T cells in the reported findings.

Sep 21, 2026

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