Selective induction of apoptosis in T-cell acute lymphoblastic leukemia by pristimerin through dual PI3K/AKT pathway inhibition and ROS generation
<p>T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy characterized by the aberrant activation of survival pathways, particularly the PI3K/AKT axis. Pristimerin (Prist), a naturally occurring quinonemethide triterpenoid, has recently gained attention for its...
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| المؤلف الرئيسي: | |
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| مؤلفون آخرون: | , , , , , , , , , , , |
| منشور في: |
2025
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| _version_ | 1864513531528871936 |
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| author | Shilpa Kuttikrishnan (3520079) |
| author2 | Zahwa Mariyam (22504034) Fareed Ahmad (134672) Mohammad Suleman (22927387) Ummu Habeeba (22504037) Anu J. Panicker (22927390) Kirti S. Prabhu (4246144) Maysaloun Merhi (4246147) Said Dermime (79420) Ammira S. Al Shabeeb Akil (22155844) Ajaz A. Bhat (12984701) Abdul W. Ansari (14557391) Shahab Uddin (154400) |
| author2_role | author author author author author author author author author author author author |
| author_facet | Shilpa Kuttikrishnan (3520079) Zahwa Mariyam (22504034) Fareed Ahmad (134672) Mohammad Suleman (22927387) Ummu Habeeba (22504037) Anu J. Panicker (22927390) Kirti S. Prabhu (4246144) Maysaloun Merhi (4246147) Said Dermime (79420) Ammira S. Al Shabeeb Akil (22155844) Ajaz A. Bhat (12984701) Abdul W. Ansari (14557391) Shahab Uddin (154400) |
| author_role | author |
| dc.creator.none.fl_str_mv | Shilpa Kuttikrishnan (3520079) Zahwa Mariyam (22504034) Fareed Ahmad (134672) Mohammad Suleman (22927387) Ummu Habeeba (22504037) Anu J. Panicker (22927390) Kirti S. Prabhu (4246144) Maysaloun Merhi (4246147) Said Dermime (79420) Ammira S. Al Shabeeb Akil (22155844) Ajaz A. Bhat (12984701) Abdul W. Ansari (14557391) Shahab Uddin (154400) |
| dc.date.none.fl_str_mv | 2025-11-08T09:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1016/j.ejphar.2025.178329 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Selective_induction_of_apoptosis_in_T-cell_acute_lymphoblastic_leukemia_by_pristimerin_through_dual_PI3K_AKT_pathway_inhibition_and_ROS_generation/30970681 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biomedical and clinical sciences Immunology Oncology and carcinogenesis Pharmacology and pharmaceutical sciences PristimerinT-cell acute lymphoblastic leukemia PI3K/AKT signaling pathway Apoptosis Cell cycle arrest Molecular docking |
| dc.title.none.fl_str_mv | Selective induction of apoptosis in T-cell acute lymphoblastic leukemia by pristimerin through dual PI3K/AKT pathway inhibition and ROS generation |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p>T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy characterized by the aberrant activation of survival pathways, particularly the PI3K/AKT axis. Pristimerin (Prist), a naturally occurring quinonemethide triterpenoid, has recently gained attention for its anti-cancer potential. In this study, we demonstrate that Prist effectively inhibits the proliferation of T-ALL cell lines (Jurkat and Molt 4) by inducing G0/G1 cell cycle arrest and triggering intrinsic and extrinsic caspase-dependent apoptosis. Prist significantly increases reactive oxygen species (ROS) levels and depletes glutathione (GSH), leading to mitochondrial dysfunction and cytochrome c release. Notably, ROS scavenging with N-acetylcysteine (NAC) abrogated Prist-induced apoptosis, highlighting ROS as a critical mediator of its cytotoxicity. Network pharmacology and molecular docking revealed AKT as a key target of Prist, with strong binding affinity confirmed through docking analysis. Prist downregulated phosphorylated AKT and inhibitor of apoptosis proteins (XIAP, cIAP1/2), supporting its pro-apoptotic mechanism. Importantly, Prist inhibited the proliferation and AKT phosphorylation in activated primary human T cells but spared resting T cells, indicating selective cytotoxicity. These findings establish Prist as a promising therapeutic candidate for T-ALL through the selective targeting of PI3K/AKT-driven survival signaling.</p><h2>Other Information</h2> <p> Published in: European Journal of Pharmacology<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.ejphar.2025.178329" target="_blank">https://dx.doi.org/10.1016/j.ejphar.2025.178329</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_01ffa1da65c0169515cd74f2479938be |
| identifier_str_mv | 10.1016/j.ejphar.2025.178329 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/30970681 |
| publishDate | 2025 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Selective induction of apoptosis in T-cell acute lymphoblastic leukemia by pristimerin through dual PI3K/AKT pathway inhibition and ROS generationShilpa Kuttikrishnan (3520079)Zahwa Mariyam (22504034)Fareed Ahmad (134672)Mohammad Suleman (22927387)Ummu Habeeba (22504037)Anu J. Panicker (22927390)Kirti S. Prabhu (4246144)Maysaloun Merhi (4246147)Said Dermime (79420)Ammira S. Al Shabeeb Akil (22155844)Ajaz A. Bhat (12984701)Abdul W. Ansari (14557391)Shahab Uddin (154400)Biomedical and clinical sciencesImmunologyOncology and carcinogenesisPharmacology and pharmaceutical sciencesPristimerinT-cell acute lymphoblastic leukemiaPI3K/AKT signaling pathwayApoptosisCell cycle arrestMolecular docking<p>T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy characterized by the aberrant activation of survival pathways, particularly the PI3K/AKT axis. Pristimerin (Prist), a naturally occurring quinonemethide triterpenoid, has recently gained attention for its anti-cancer potential. In this study, we demonstrate that Prist effectively inhibits the proliferation of T-ALL cell lines (Jurkat and Molt 4) by inducing G0/G1 cell cycle arrest and triggering intrinsic and extrinsic caspase-dependent apoptosis. Prist significantly increases reactive oxygen species (ROS) levels and depletes glutathione (GSH), leading to mitochondrial dysfunction and cytochrome c release. Notably, ROS scavenging with N-acetylcysteine (NAC) abrogated Prist-induced apoptosis, highlighting ROS as a critical mediator of its cytotoxicity. Network pharmacology and molecular docking revealed AKT as a key target of Prist, with strong binding affinity confirmed through docking analysis. Prist downregulated phosphorylated AKT and inhibitor of apoptosis proteins (XIAP, cIAP1/2), supporting its pro-apoptotic mechanism. Importantly, Prist inhibited the proliferation and AKT phosphorylation in activated primary human T cells but spared resting T cells, indicating selective cytotoxicity. These findings establish Prist as a promising therapeutic candidate for T-ALL through the selective targeting of PI3K/AKT-driven survival signaling.</p><h2>Other Information</h2> <p> Published in: European Journal of Pharmacology<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.ejphar.2025.178329" target="_blank">https://dx.doi.org/10.1016/j.ejphar.2025.178329</a></p>2025-11-08T09:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1016/j.ejphar.2025.178329https://figshare.com/articles/journal_contribution/Selective_induction_of_apoptosis_in_T-cell_acute_lymphoblastic_leukemia_by_pristimerin_through_dual_PI3K_AKT_pathway_inhibition_and_ROS_generation/30970681CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/309706812025-11-08T09:00:00Z |
| spellingShingle | Selective induction of apoptosis in T-cell acute lymphoblastic leukemia by pristimerin through dual PI3K/AKT pathway inhibition and ROS generation Shilpa Kuttikrishnan (3520079) Biomedical and clinical sciences Immunology Oncology and carcinogenesis Pharmacology and pharmaceutical sciences PristimerinT-cell acute lymphoblastic leukemia PI3K/AKT signaling pathway Apoptosis Cell cycle arrest Molecular docking |
| status_str | publishedVersion |
| title | Selective induction of apoptosis in T-cell acute lymphoblastic leukemia by pristimerin through dual PI3K/AKT pathway inhibition and ROS generation |
| title_full | Selective induction of apoptosis in T-cell acute lymphoblastic leukemia by pristimerin through dual PI3K/AKT pathway inhibition and ROS generation |
| title_fullStr | Selective induction of apoptosis in T-cell acute lymphoblastic leukemia by pristimerin through dual PI3K/AKT pathway inhibition and ROS generation |
| title_full_unstemmed | Selective induction of apoptosis in T-cell acute lymphoblastic leukemia by pristimerin through dual PI3K/AKT pathway inhibition and ROS generation |
| title_short | Selective induction of apoptosis in T-cell acute lymphoblastic leukemia by pristimerin through dual PI3K/AKT pathway inhibition and ROS generation |
| title_sort | Selective induction of apoptosis in T-cell acute lymphoblastic leukemia by pristimerin through dual PI3K/AKT pathway inhibition and ROS generation |
| topic | Biomedical and clinical sciences Immunology Oncology and carcinogenesis Pharmacology and pharmaceutical sciences PristimerinT-cell acute lymphoblastic leukemia PI3K/AKT signaling pathway Apoptosis Cell cycle arrest Molecular docking |