Identification of a novel chalcone derivative that inhibits Notch signaling in T-cell acute lymphoblastic leukemia.
AffiliationCenter for Life Nano Science@Sapienza, Istituto Italiano di Tecnologia, Rome, 00161, Italy
MetadataShow full item record
AbstractNotch signaling is considered a rational target in the therapy of several cancers, particularly those harbouring Notch gain of function mutations, including T-cell acute lymphoblastic leukemia (T-ALL). Although currently available Notch-blocking agents are showing anti-tumor activity in preclinical studies, they are not effective in all the patients and often cause severe side-effects, limiting their widespread therapeutic use. Here, by functional and biological analysis of the most representative molecules of an in house library of natural products, we have designed and synthetized the chalcone-derivative 8 possessing Notch inhibitory activity at low micro molar concentration in T-ALL cell lines. Structure-activity relationships were afforded for the chalcone scaffold. Short term treatments with compound 8 resulted in a dose-dependent decrease of Notch signaling activity, halted cell cycle progression and induced apoptosis, thus affecting leukemia cell growth. Taken together, our data indicate that 8 is a novel Notch inhibitor, candidate for further investigation and development as an additional therapeutic option against Notch-dependent cancers.
CitationIdentification of a novel chalcone derivative that inhibits Notch signaling in T-cell acute lymphoblastic leukemia. 2017, 7 (1):2213 Sci Rep
- Investigation of deregulated genes of Notch signaling pathway in human T cell acute lymphoblastic leukemia cell lines and clinical samples.
- Authors: Paryan M, Mohammadi-Yeganeh S, Samiee SM, Soleimani M, Arefian E, Azadmanesh K, Poopak B, Mostafavi E, Karimipoor M, Mahdian R
- Issue date: 2013 Oct
- Notch signaling as a therapeutic target for acute lymphoblastic leukemia.
- Authors: Bellavia D, Palermo R, Felli MP, Screpanti I, Checquolo S
- Issue date: 2018 Apr
- Notch and NF-kB signaling pathways regulate miR-223/FBXW7 axis in T-cell acute lymphoblastic leukemia.
- Authors: Kumar V, Palermo R, Talora C, Campese AF, Checquolo S, Bellavia D, Tottone L, Testa G, Miele E, Indraccolo S, Amadori A, Ferretti E, Gulino A, Vacca A, Screpanti I
- Issue date: 2014 Dec
- PI3K/mTOR inhibition upregulates NOTCH-MYC signalling leading to an impaired cytotoxic response.
- Authors: Shepherd C, Banerjee L, Cheung CW, Mansour MR, Jenkinson S, Gale RE, Khwaja A
- Issue date: 2013 Mar
- Inhibition of NOTCH signaling by gamma secretase inhibitor engages the RB pathway and elicits cell cycle exit in T-cell acute lymphoblastic leukemia cells.
- Authors: Rao SS, O'Neil J, Liberator CD, Hardwick JS, Dai X, Zhang T, Tyminski E, Yuan J, Kohl NE, Richon VM, Van der Ploeg LH, Carroll PM, Draetta GF, Look AT, Strack PR, Winter CG
- Issue date: 2009 Apr 1