Show simple item record

AuthorKuttikrishnan, Shilpa
AuthorMasoodi, Tariq
AuthorAhmad, Fareed
AuthorSher, Gulab
AuthorPrabhu, Kirti S.
AuthorMateo, Jericha M.
AuthorBuddenkotte, Joerg
AuthorEl-Elimat, Tamam
AuthorOberlies, Nicholas H.
AuthorPearce, Cedric J.
AuthorBhat, Ajaz A.
AuthorAlali, Feras Q.
AuthorSteinhoff, Martin
AuthorUddin, Shahab
Available date2024-03-13T05:14:57Z
Publication Date2023
Publication NameJournal of Dermatological Science
ResourceScopus
ISSN9231811
URIhttp://dx.doi.org/10.1016/j.jdermsci.2023.10.001
URIhttp://hdl.handle.net/10576/52976
AbstractBackground: 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.
SponsorThis work was supported by the grants funded by the Medical Research center (MRC), Hamad Medical Corporation , Doha, Qatar ( MRC-01-21-301 ).
Languageen
PublisherElsevier
Subjectbortezomib
caspase 3
forkhead box protein M1
natural product
neosetophomone B
nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase
S phase kinase associated protein 2
unclassified drug
aurora A kinase
forkhead box protein M1
FOXM1 protein, human
antineoplastic activity
apoptosis
Article
cell viability
combination drug therapy
controlled study
cutaneous T cell lymphoma
cytolysis
double stranded DNA break
down regulation
drug efficacy
drug potentiation
drug targeting
enzyme activation
gene expression profiling
gene silencing
H9 cell line
IC50
in vitro study
mitochondrial membrane potential
monotherapy
proapoptotic activity
signal transduction
human
metabolism
pathology
skin tumor
tumor cell line
Apoptosis
Aurora Kinase A
Cell Line, Tumor
Forkhead Box Protein M1
Humans
Lymphoma, T-Cell, Cutaneous
Signal Transduction
Skin Neoplasms
TitleIn vitro evaluation of Neosetophomone B inducing apoptosis in cutaneous T cell lymphoma by targeting the FOXM1 signaling pathway
TypeArticle
Pagination83-91
Issue Number2
Volume Number112


Files in this item

FilesSizeFormatView

There are no files associated with this item.

This item appears in the following Collection(s)

Show simple item record