Identification of a novel chalcone derivative that inhibits Notch signaling in T-cell acute lymphoblastic leukemia.
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Authors
Mori, MTottone, L
Quaglio, D
Zhdanovskaya, N
Ingallina, C
Fusto, M
Ghirga, F
Peruzzi, G
Crestoni, M
Simeoni, Fabrizio
Giulimondi, F
Talora, C
Botta, B
Screpanti, I
Palermo, R
Affiliation
Center for Life Nano Science@Sapienza, Istituto Italiano di Tecnologia, Rome, 00161, ItalyIssue Date
2017-05-19
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Notch 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.Citation
Identification of a novel chalcone derivative that inhibits Notch signaling in T-cell acute lymphoblastic leukemia. 2017, 7 (1):2213 Sci RepJournal
Scientific ReportsDOI
10.1038/s41598-017-02316-9PubMed ID
28526832Type
ArticleLanguage
enISSN
2045-2322ae974a485f413a2113503eed53cd6c53
10.1038/s41598-017-02316-9
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