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AuthorMalki, Ahmed
AuthorElbayaa, Rasha Y.
AuthorAshour, Hayam M.A.
AuthorLoffredo, Christopher A.
AuthorYoussef, Amal M.
Available date2024-03-30T08:55:35Z
Publication Date2015-08-27
Publication NameJournal of Enzyme Inhibition and Medicinal Chemistry
Identifierhttp://dx.doi.org/10.3109/14756366.2014.971781
CitationMalki, A., Elbayaa, R. Y., Ashour, H. M., Loffredo, C. A., & Youssef, A. M. (2015). Novel thiosemicarbazides induced apoptosis in human MCF-7 breast cancer cells via JNK signaling. Journal of Enzyme Inhibition and Medicinal Chemistry, 30(5), 786-795.
ISSN14756366
ISSN1475-6366
URIhttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84940756126&origin=inward
URIhttp://hdl.handle.net/10576/53721
AbstractIn this study, novel thiosemicarbazides and 1,3,4-oxadiazoles were synthesized and evaluated for their anticancer effects on human MCF-7 breast cancer cell lines. Among the synthesized derivatives studied, compound 2-(3-(4-chlorophenyl)-3-hydroxybutanoyl)-N-phenylhydrazinecarbothioamide 4c showed the highest cytotoxicity against MCF-7 breast cancer cells as it reduced cell viability to approximately 15% compared to approximately 25% in normal breast epithelial cells. Therefore, we focused on 4c for further investigations. Our data showed that 4c induced apoptosis in MCF-7 cells which was further confirmed by TUNEL assay. Western blotting analysis showed that compound 4c up-regulated the pro-survival proteins Bax, Bad and ERK1/2, while it down-regulated anti-apoptotic proteins Bcl-2, Akt and STAT-3. Additionally, 4c induced phosphorylation of SAPK/JNK in MCF-7 cells. Pretreatment of MCF-7 cells with 10 μM of JNK inhibitor significantly reduced 4c-induced apoptosis. Molecular docking results suggested that compound 4c showed a binding pattern close to the pattern observed in the structure of the lead fragment bound to JNK1. Collectively, the data of current study suggested that the thiosemicarbazide 4c might trigger apoptosis in human MCF-7 cells by targeting JNK signaling.
SponsorThis work was partially supported by the Department of Health Sciences, Qatar University.
Languageen
PublisherTaylor & Francis
Subject1,3,4-Oxadiazoles
apoptosis
docking
flow cytometry
JNK signaling
MCF-7 breast cancer cells
thiosemicarbazides
TitleNovel thiosemicarbazides induced apoptosis in human MCF-7 breast cancer cells via JNK signaling
TypeArticle
Issue Number5
Volume Number30
ESSN1475-6374
dc.accessType Full Text


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