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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2025
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| Summary: | <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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