Growth inhibitory effects of Withaferin A on MDS-L cells – A human 5q Myelodysplastic Syndrome (MDS) cell line
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Le résumé fourni par la source
Abstract Myelodysplastic syndrome (MDS) affects bone marrow production of white blood cells and erythrocytes. At least 40% of MDS patients who go into remission after treatment eventually progress to acute myelogenous leukemia (AML) which is very difficult to treat. Hence, there is a compelling need for new and better therapies. Withaferin A (WFA), a withanolide isolated from Winter cherry (Withania somnifera), has been shown to have potent anti-cancer properties in several animal models of cancer. We found that WFA inhibited the growth of MDS-L cells, a human cell line derived from a 5q MDS patient. Treatment with WFA induced apoptosis of MDS-L cells, indicated by the cleavage of caspase-3 as early as 6hrs after treatment and a dose dependent increase of annexin positive cells. Cell cycle analysis revealed that WFA caused MDS-L cells to arrest at S and G2/M and accordingly there was a reduction in cyclin A/CDK2 and cyclin B/CDK1 respectively. WFA also inhibited the activity of the heat shock protein (Hsp 90) chaperone as shown by the degradation of its client proteins such as Akt, an important pro-survival kinase and increased expression of Hsp70 which partially compensates for decrease in Hsp90 function. Interestingly, the mechanism by which WFA acts on MDS-L cells is independent of its well-recognized action on Nf-κB. Microarray analysis of gene expression in MDS-L cells showed a dramatic increase in several genes that may have a role in Nf-κB independent growth inhibitory effects of WFA. Studies with a xenograft model of MDS-L cells in NSGS mice suggest WFA might also be effective in vivo. The potent anti-proliferative and anti-survival effects of WFA on MDS-L cells, suggest that it could be a novel therapeutic agent for the treatment of 5q MDS.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Growth inhibitory effects of Withaferin A on MDS-L cells – A human 5q Myelodysplastic Syndrome (MDS) cell line
- Date Crossref
- 01/05/2016
- Éditeur
- Oxford University Press (OUP)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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University of Kentucky pays non établi dans la noticeUniversité ou école supérieure
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Cincinnati Children's Hospital Medical Center pays non établi dans la noticeÉtablissement de santé
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University of Louisville pays non établi dans la noticeUniversité ou école supérieure
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University of Louisville Hospital pays non établi dans la noticeÉtablissement de santé
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Univ. of Kentucky pays non établi dans la noticeInstitution
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Cincinnati Children’s Hosp. Med. Ctr pays non établi dans la noticeInstitution
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Univ. of Louisville pays non établi dans la noticeInstitution
University of Kentucky, Cincinnati Children's Hospital Medical Center et University of Louisville, avec 4 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.