RNA-Seq reveals novel mechanistic targets of withaferin A (WA) in prostate cancer cells
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ABSTRACT:
PROVIDER: PRJNA565770 | ENA |
REPOSITORIES: ENA
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Project description:RNA-Seq analysis using WA-treated 22Rv1 human prostate cancer cells revealed upregulation and downregulation of 6993 and 6607 genes, respectively when compared to the vehicle-treated control. The pathways with significantly upregulated gene expression following WA treatment included mitogen-activated protein kinases, focal adhesion, endocytosis, and autophagy as revealed by KEGG and gene ontology analyses. WA treatment also resulted in downregulation of genes associated with metabolic pathways, oxidative phosphorylation, tricarboxylic acid cycle, cell cycle, and base excision repair. This study identifies novel mechanistic targets of WA in prostate cancer.
2019-09-17 | GSE137519 | GEO
Project description:Withaferin A (WA), a major chemical component of an Indian herb Withania somnifera, induces cell death (apoptosis/necrosis) in a variety of tumor cells, but its molecular mechanism remains elusive. We report that WA induces cell death selectively in high-grade prostate (PC-3 and DU-145) and tongue (SAS) cancer cells but not in normal human fibroblast (TIG-1) and low-grade prostate cancer (LNCaP) cells.
2015-08-02 | GSE55728 | GEO
Project description:Withaferin A (WA), a major chemical component of an Indian herb Withania somnifera, induces cell death (apoptosis/necrosis) in a variety of tumor cells, but its molecular mechanism remains elusive. We report that WA induces cell death selectively in high-grade prostate (PC-3 and DU-145) and tongue (SAS) cancer cells but not in normal human fibroblast (TIG-1) and low-grade prostate cancer (LNCaP) cells. To identify genes whose expression levels were up- or down-regulated in prostate cancer cells following WA treatment, we examined the transcriptome profiles of mRNA prepared from TIG-1, LNCaP, PC-3 and DU-145 cells using Agilent’s Whole Human Genome Microarray.
2015-08-02 | E-GEOD-55728 | biostudies-arrayexpress
Project description:Withaferin A (WA) is a lactone extracted from Withania somnifera commonly known as Ashwagandha. WA has several therapeutic benefits. The current study was aimed to identify biomarkers that could be targeted by WA in prostate cancer (PCA) cells. We have used SILAC approach to identify WA-regulated proteins at 4 h and 24 time points in three PCA cell lines such as LNCaP, 22Rv1 and DU-145. Ontology prediction suggested that WA treatment can upregulate stress-responsive pathways and shutdown translation and cell metabolism to conserve energy. The cytoprotective stress granule (SG) protein G3BP1 showed upregulation in all the three tested cell lines in response to WA treatment, and subsequently, SGs formed at a higher rate in the WA treated cells. Knockdown (KD) of G3BP1 blocked WA-induced SG formation and reduced the cell survival. We speculate that the activation of G3BP1 and the formation of SGs might constitute a mechanism by which PCA cells induce cell protection after WA- treatment. Knock down of SG proteins such as G3BP1 could help to evade the cytoprotective effects of WA and to assist in the sensitization of cells.
2021-07-21 | PXD016759 | Pride
Project description:Novel cancer-selective and disease subtype-independent mechanistic targets of withaferin A in human breast cancer cells
| PRJNA663908 | ENA
Project description:We report differential gene expression changes by withaferin A in breast cancer cells versus a normal mammary epithelial cell line.
2020-09-17 | GSE158085 | GEO
Project description:Withaferin A (WA), a natural steroid lactone from the plant Withania Somnifera, has been used for many years in traditional Ayurveda medicine to treat inflammation-related conditions, such as ulcers and rheumatism. Today, WA is most often studied because of its antitumor properties. Although many in vitro and in vivo studies have been performed, the identification of Withaferin A protein targets and of its mechanism of antitumor action remains incomplete. Here, we used quantitative chemoproteomics and differential protein expression analysis to characterize the WA antitumor effects on a multiple myeloma cell model. Identified relevant targets were further validated by Ingenuity Pathway Analysis (IPA) and Western Blot. Canonical pathway analysis revealed targeting of the ubiquitination pathway as a main strategy for WA-induced cell death. Further data suggested that WA targets protein networks that are specific for monoclonal gammopathy of undetermined significance (MGUS) and other closely related disorders, such as multiple myeloma (MM) and Waldenström macroglobulinemia (WM). Moreover, 16 of 20 proteins influenced by WA potentially counteract disease progression, suggesting WA can be used as an effective treatment for MGUS and other closely related disorders.
2018-02-23 | PXD006528 | Pride
Project description:High-risk neuroblastoma is a devastating malignancy with few therapeutic options. We identify withaferin A (WA) as a natural ferroptosis inducing agent in neuroblastoma, which acts through a novel double-edged mechanism. WA targets and inactivates glutathione peroxidase 4, as well as increases intracellular labile Fe(II) upon excessive activation of heme oxygenase-1, which both independently result in ferroptosis. This double-edged mechanism results in a high efficacy of WA compared to etoposide in killing a heterogeneous panel of high-risk neuroblastoma cells, and in suppressing neuroblastoma xenografts growth and relapse rate. Nano-targeting of WA allows systemic application and suppressed tumor growth due to an enhanced targeting to the tumor site. Collectively, our data propose a novel therapeutic strategy to kill cancer cells by ferroptosis. High-risk neuroblastoma is a devastating malignancy with few therapeutic options. We identify withaferin A (WA) as a natural ferroptosis inducing agent in neuroblastoma, which acts through a novel double-edged mechanism. WA targets and inactivates glutathione peroxidase 4, as well as increases intracellular labile Fe(II) upon excessive activation of heme oxygenase-1, which both independently result in ferroptosis. This double-edged mechanism results in a high efficacy of WA compared to etoposide in killing a heterogeneous panel of high-risk neuroblastoma cells, and in suppressing neuroblastoma xenografts growth and relapse rate. Nano-targeting of WA allows systemic application and suppressed tumor growth due to an enhanced targeting to the tumor site. Collectively, our data propose a novel therapeutic strategy to kill cancer cells by ferroptosis.
2018-05-01 | GSE112384 | GEO
Project description:Withaferin A (WA) causes cell death in prostate cells.
| PRJNA240808 | ENA
Project description:Beauveria bassiana strain:WA | isolate:sp | breed:WA | cultivar:WA Transcriptome or Gene expression
| PRJNA450459 | ENA