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...
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| مؤلفون آخرون: | , , , , , , , |
| منشور في: |
2025
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| _version_ | 1864513532024848384 |
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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> |
| eu_rights_str_mv | openAccess |
| id | Manara2_331300bff0ce2b450afdde694dd8971f |
| identifier_str_mv | 10.1016/j.taap.2025.117403 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/30819881 |
| publishDate | 2025 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| 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 |