Shilpa Kuttikrishnan , Tariq Masoodi , Fareed Ahmad , Gulab Sher , Kirti S. Prabhu , Jericha M. Mateo , Joerg Buddenkotte , Tamam El-Elimat , Nicholas H. Oberlies , Cedric J. Pearce , Ajaz A. Bhat , Feras Q. Alali , Martin Steinhoff , Shahab Uddin
{"title":"靶向FOXM1信号通路诱导皮肤T细胞淋巴瘤细胞凋亡的体外评价。","authors":"Shilpa Kuttikrishnan , Tariq Masoodi , Fareed Ahmad , Gulab Sher , Kirti S. Prabhu , Jericha M. Mateo , Joerg Buddenkotte , Tamam El-Elimat , Nicholas H. Oberlies , Cedric J. Pearce , Ajaz A. Bhat , Feras Q. Alali , Martin Steinhoff , Shahab Uddin","doi":"10.1016/j.jdermsci.2023.10.001","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>Cutaneous T cell lymphoma<span> (CTCL) is a T cell-derived non-Hodgkin lymphoma primarily affecting the skin, with treatment posing a significant challenge and low survival rates.</span></p></div><div><h3>Objective</h3><p>In this study, we investigated the anti-cancer potential of Neosetophomone B (NSP-B), a fungal-derived secondary metabolite, on CTCL cell lines H9 and HH.</p></div><div><h3>Methods</h3><p><span><span>Cell viability was measured using Cell counting Kit-8 (CCK8) assays. </span>Apoptosis<span> was measured by annexin V/PI dual staining. Immunoblotting was performed to examine the expression of proteins. Applied Biosystems' high-resolution Human </span></span>Transcriptome Array 2.0 was used to examine gene expression.</p></div><div><h3>Results</h3><p><span><span>NSP-B induced apoptosis in CTCL cells by activating mitochondrial signaling pathways and </span>caspases<span>. We observed downregulated expression of BUB1B, Aurora Kinases A and B, cyclin-dependent kinases (CDKs) 4 and 6, and polo-like kinase 1 (PLK1) in NSP-B treated cells, which was further corroborated by Western blot analysis. Notably, higher expression levels of these genes showed reduced overall and progression-free survival in the CTCL patient cohort. FOXM1 and BUB1B expression exhibited a dose-dependent reduction in NSP-B-treated CTCL cells.FOXM1 silencing decreased cell viability and increased apoptosis via BUB1B downregulation. Moreover, NSP-B suppressed FOXM1-regulated genes, such as Aurora Kinases A and B, CDKs 4 and 6, and PLK1. The combined treatment of </span></span>Bortezomib and NSP-B showed greater efficacy in reducing CTCL cell viability and promoting apoptosis compared to either treatment alone.</p></div><div><h3>Conclusion</h3><p>Our findings suggest that targeting the FOXM1 pathway may provide a promising therapeutic strategy for CTCL management, with NSP-B offering significant potential as a novel treatment option.</p></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":null,"pages":null},"PeriodicalIF":4.6000,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"In vitro evaluation of Neosetophomone B inducing apoptosis in cutaneous T cell lymphoma by targeting the FOXM1 signaling pathway\",\"authors\":\"Shilpa Kuttikrishnan , Tariq Masoodi , Fareed Ahmad , Gulab Sher , Kirti S. Prabhu , Jericha M. Mateo , Joerg Buddenkotte , Tamam El-Elimat , Nicholas H. Oberlies , Cedric J. Pearce , Ajaz A. Bhat , Feras Q. Alali , Martin Steinhoff , Shahab Uddin\",\"doi\":\"10.1016/j.jdermsci.2023.10.001\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>Cutaneous T cell lymphoma<span> (CTCL) is a T cell-derived non-Hodgkin lymphoma primarily affecting the skin, with treatment posing a significant challenge and low survival rates.</span></p></div><div><h3>Objective</h3><p>In this study, we investigated the anti-cancer potential of Neosetophomone B (NSP-B), a fungal-derived secondary metabolite, on CTCL cell lines H9 and HH.</p></div><div><h3>Methods</h3><p><span><span>Cell viability was measured using Cell counting Kit-8 (CCK8) assays. </span>Apoptosis<span> was measured by annexin V/PI dual staining. Immunoblotting was performed to examine the expression of proteins. Applied Biosystems' high-resolution Human </span></span>Transcriptome Array 2.0 was used to examine gene expression.</p></div><div><h3>Results</h3><p><span><span>NSP-B induced apoptosis in CTCL cells by activating mitochondrial signaling pathways and </span>caspases<span>. We observed downregulated expression of BUB1B, Aurora Kinases A and B, cyclin-dependent kinases (CDKs) 4 and 6, and polo-like kinase 1 (PLK1) in NSP-B treated cells, which was further corroborated by Western blot analysis. Notably, higher expression levels of these genes showed reduced overall and progression-free survival in the CTCL patient cohort. FOXM1 and BUB1B expression exhibited a dose-dependent reduction in NSP-B-treated CTCL cells.FOXM1 silencing decreased cell viability and increased apoptosis via BUB1B downregulation. Moreover, NSP-B suppressed FOXM1-regulated genes, such as Aurora Kinases A and B, CDKs 4 and 6, and PLK1. The combined treatment of </span></span>Bortezomib and NSP-B showed greater efficacy in reducing CTCL cell viability and promoting apoptosis compared to either treatment alone.</p></div><div><h3>Conclusion</h3><p>Our findings suggest that targeting the FOXM1 pathway may provide a promising therapeutic strategy for CTCL management, with NSP-B offering significant potential as a novel treatment option.</p></div>\",\"PeriodicalId\":94076,\"journal\":{\"name\":\"Journal of dermatological science\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2023-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of dermatological science\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0923181123002244\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of dermatological science","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0923181123002244","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
In vitro evaluation of Neosetophomone B inducing apoptosis in cutaneous T cell lymphoma by targeting the FOXM1 signaling pathway
Background
Cutaneous T cell lymphoma (CTCL) is a T cell-derived non-Hodgkin lymphoma primarily affecting the skin, with treatment posing a significant challenge and low survival rates.
Objective
In this study, we investigated the anti-cancer potential of Neosetophomone B (NSP-B), a fungal-derived secondary metabolite, on CTCL cell lines H9 and HH.
Methods
Cell viability was measured using Cell counting Kit-8 (CCK8) assays. Apoptosis was measured by annexin V/PI dual staining. Immunoblotting was performed to examine the expression of proteins. Applied Biosystems' high-resolution Human Transcriptome Array 2.0 was used to examine gene expression.
Results
NSP-B induced apoptosis in CTCL cells by activating mitochondrial signaling pathways and caspases. We observed downregulated expression of BUB1B, Aurora Kinases A and B, cyclin-dependent kinases (CDKs) 4 and 6, and polo-like kinase 1 (PLK1) in NSP-B treated cells, which was further corroborated by Western blot analysis. Notably, higher expression levels of these genes showed reduced overall and progression-free survival in the CTCL patient cohort. FOXM1 and BUB1B expression exhibited a dose-dependent reduction in NSP-B-treated CTCL cells.FOXM1 silencing decreased cell viability and increased apoptosis via BUB1B downregulation. Moreover, NSP-B suppressed FOXM1-regulated genes, such as Aurora Kinases A and B, CDKs 4 and 6, and PLK1. The combined treatment of Bortezomib and NSP-B showed greater efficacy in reducing CTCL cell viability and promoting apoptosis compared to either treatment alone.
Conclusion
Our findings suggest that targeting the FOXM1 pathway may provide a promising therapeutic strategy for CTCL management, with NSP-B offering significant potential as a novel treatment option.