Curcumin induces apoptosis via downregulation of SKP2 and induction of GADD45A/CDKN1A expression through generation of ROS in cutaneous T-cell lymphoma cells

<p dir="ltr"><u>Curcumin</u>, a plant derived <u>natural product</u> isolated from <u>Curcuma</u> longa. The aim of this study is to investigate the anti-proliferative effects and the underlying mechanisms of curcumin in Cutaneous <u>T cell&l...

وصف كامل

محفوظ في:
التفاصيل البيبلوغرافية
المؤلف الرئيسي: Shilpa Kuttikrishnan (3520079) (author)
مؤلفون آخرون: Muhammad Suleman (3829027) (author), Fareed Ahmad (134672) (author), Zahwa Mariyam (22504034) (author), Ummu Habeeba (22504037) (author), Kirti S. Prabhu (4246144) (author), Joerg Buddenkotte (6293584) (author), Martin Steinhoff (5340194) (author), Shahab Uddin (154400) (author)
منشور في: 2025
الموضوعات:
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author Shilpa Kuttikrishnan (3520079)
author2 Muhammad Suleman (3829027)
Fareed Ahmad (134672)
Zahwa Mariyam (22504034)
Ummu Habeeba (22504037)
Kirti S. Prabhu (4246144)
Joerg Buddenkotte (6293584)
Martin Steinhoff (5340194)
Shahab Uddin (154400)
author2_role author
author
author
author
author
author
author
author
author_facet Shilpa Kuttikrishnan (3520079)
Muhammad Suleman (3829027)
Fareed Ahmad (134672)
Zahwa Mariyam (22504034)
Ummu Habeeba (22504037)
Kirti S. Prabhu (4246144)
Joerg Buddenkotte (6293584)
Martin Steinhoff (5340194)
Shahab Uddin (154400)
author_role author
dc.creator.none.fl_str_mv Shilpa Kuttikrishnan (3520079)
Muhammad Suleman (3829027)
Fareed Ahmad (134672)
Zahwa Mariyam (22504034)
Ummu Habeeba (22504037)
Kirti S. Prabhu (4246144)
Joerg Buddenkotte (6293584)
Martin Steinhoff (5340194)
Shahab Uddin (154400)
dc.date.none.fl_str_mv 2025-05-26T12:00:00Z
dc.identifier.none.fl_str_mv 10.1016/j.taap.2025.117403
dc.relation.none.fl_str_mv https://figshare.com/articles/journal_contribution/Curcumin_induces_apoptosis_via_downregulation_of_SKP2_and_induction_of_GADD45A_CDKN1A_expression_through_generation_of_ROS_in_cutaneous_T-cell_lymphoma_cells/30819881
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
Clinical sciences
Oncology and carcinogenesis
Pharmacology and pharmaceutical sciences
Curcumin
CTCL
SKP2
GADD45
Apoptosis
Caspases
dc.title.none.fl_str_mv Curcumin induces apoptosis via downregulation of SKP2 and induction of GADD45A/CDKN1A expression through generation of ROS in cutaneous T-cell lymphoma cells
dc.type.none.fl_str_mv Text
Journal contribution
info:eu-repo/semantics/publishedVersion
text
contribution to journal
description <p dir="ltr"><u>Curcumin</u>, a plant derived <u>natural product</u> isolated from <u>Curcuma</u> longa. The aim of this study is to investigate the anti-proliferative effects and the underlying mechanisms of curcumin in Cutaneous <u>T cell</u> lymphoma (CTCL), a type of non-Hodgkin lymphoma that primarily affects the skin. The study found that curcumin induced apoptosis in CTCL cells by activating mitochondrial <u>signaling pathways</u> and <u>caspases</u> leading to growth inhibition. Furthermore, Curcumin treatment downregulated the expression of S-phase <u>kinase protein</u> (SKP2) with concomitant upregulation of GADD45A,<u> CDKN1A</u> and <u>CDKN1B</u>. Curcumin also suppresses the expression of anti-apoptotic molecules including <u>XIAP</u> and cIAPs. Curcumin treatment of CTCL cells generates <u>reactive oxygen species</u> (ROS) and depletion of <u>glutathione</u>. Pretreatment of CTCL with <i>N</i>-acetyl cysteine prevented curcumin-mediated generation of ROS and prevention caspase activity. Co-treatment of CTCL with subtoxic doses of curcumin and <u>bortezomib </u>potentiated the <u>anticancer action</u>. </p><p dir="ltr">Co-treatment of CTCL with subtoxic doses of curcumin and bortezomib potentiated the anticancer action. <u>Molecular docking</u> studies revealed a strong binding affinity of curcumin to the active site of SKP2, primarily involving key residues crucial for its activity. </p><p dir="ltr">Altogether, our results suggest that targeting SKP2 and GADD45A signaling by curcumin could be an attractive strategy for the treatment of CTCL.</p><h2>Other Information</h2><p dir="ltr">Published in: Toxicology and Applied 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.taap.2025.117403" target="_blank">https://dx.doi.org/10.1016/j.taap.2025.117403</a></p>
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network_acronym_str Manara2
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oai_identifier_str oai:figshare.com:article/30819881
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spelling Curcumin induces apoptosis via downregulation of SKP2 and induction of GADD45A/CDKN1A expression through generation of ROS in cutaneous T-cell lymphoma cellsShilpa Kuttikrishnan (3520079)Muhammad Suleman (3829027)Fareed Ahmad (134672)Zahwa Mariyam (22504034)Ummu Habeeba (22504037)Kirti S. Prabhu (4246144)Joerg Buddenkotte (6293584)Martin Steinhoff (5340194)Shahab Uddin (154400)Biomedical and clinical sciencesClinical sciencesOncology and carcinogenesisPharmacology and pharmaceutical sciencesCurcuminCTCLSKP2GADD45ApoptosisCaspases<p dir="ltr"><u>Curcumin</u>, a plant derived <u>natural product</u> isolated from <u>Curcuma</u> longa. The aim of this study is to investigate the anti-proliferative effects and the underlying mechanisms of curcumin in Cutaneous <u>T cell</u> lymphoma (CTCL), a type of non-Hodgkin lymphoma that primarily affects the skin. The study found that curcumin induced apoptosis in CTCL cells by activating mitochondrial <u>signaling pathways</u> and <u>caspases</u> leading to growth inhibition. Furthermore, Curcumin treatment downregulated the expression of S-phase <u>kinase protein</u> (SKP2) with concomitant upregulation of GADD45A,<u> CDKN1A</u> and <u>CDKN1B</u>. Curcumin also suppresses the expression of anti-apoptotic molecules including <u>XIAP</u> and cIAPs. Curcumin treatment of CTCL cells generates <u>reactive oxygen species</u> (ROS) and depletion of <u>glutathione</u>. Pretreatment of CTCL with <i>N</i>-acetyl cysteine prevented curcumin-mediated generation of ROS and prevention caspase activity. Co-treatment of CTCL with subtoxic doses of curcumin and <u>bortezomib </u>potentiated the <u>anticancer action</u>. </p><p dir="ltr">Co-treatment of CTCL with subtoxic doses of curcumin and bortezomib potentiated the anticancer action. <u>Molecular docking</u> studies revealed a strong binding affinity of curcumin to the active site of SKP2, primarily involving key residues crucial for its activity. </p><p dir="ltr">Altogether, our results suggest that targeting SKP2 and GADD45A signaling by curcumin could be an attractive strategy for the treatment of CTCL.</p><h2>Other Information</h2><p dir="ltr">Published in: Toxicology and Applied 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.taap.2025.117403" target="_blank">https://dx.doi.org/10.1016/j.taap.2025.117403</a></p>2025-05-26T12:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1016/j.taap.2025.117403https://figshare.com/articles/journal_contribution/Curcumin_induces_apoptosis_via_downregulation_of_SKP2_and_induction_of_GADD45A_CDKN1A_expression_through_generation_of_ROS_in_cutaneous_T-cell_lymphoma_cells/30819881CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/308198812025-05-26T12:00:00Z
spellingShingle Curcumin induces apoptosis via downregulation of SKP2 and induction of GADD45A/CDKN1A expression through generation of ROS in cutaneous T-cell lymphoma cells
Shilpa Kuttikrishnan (3520079)
Biomedical and clinical sciences
Clinical sciences
Oncology and carcinogenesis
Pharmacology and pharmaceutical sciences
Curcumin
CTCL
SKP2
GADD45
Apoptosis
Caspases
status_str publishedVersion
title Curcumin induces apoptosis via downregulation of SKP2 and induction of GADD45A/CDKN1A expression through generation of ROS in cutaneous T-cell lymphoma cells
title_full Curcumin induces apoptosis via downregulation of SKP2 and induction of GADD45A/CDKN1A expression through generation of ROS in cutaneous T-cell lymphoma cells
title_fullStr Curcumin induces apoptosis via downregulation of SKP2 and induction of GADD45A/CDKN1A expression through generation of ROS in cutaneous T-cell lymphoma cells
title_full_unstemmed Curcumin induces apoptosis via downregulation of SKP2 and induction of GADD45A/CDKN1A expression through generation of ROS in cutaneous T-cell lymphoma cells
title_short Curcumin induces apoptosis via downregulation of SKP2 and induction of GADD45A/CDKN1A expression through generation of ROS in cutaneous T-cell lymphoma cells
title_sort Curcumin induces apoptosis via downregulation of SKP2 and induction of GADD45A/CDKN1A expression through generation of ROS in cutaneous T-cell lymphoma cells
topic Biomedical and clinical sciences
Clinical sciences
Oncology and carcinogenesis
Pharmacology and pharmaceutical sciences
Curcumin
CTCL
SKP2
GADD45
Apoptosis
Caspases