Synthesis, characterization and apoptotic activity of quinazolinone Schiff base derivatives toward MCF-7 cells via intrinsic and extrinsic apoptosis pathways

Zahedifard, M. and Faraj, F.L. and Paydar, M. and Looi, C.Y. and Hajrezaei, M. and Hasanpourghadi, M. and Kamalidehghan, B. and Majid, N.A. and Ali, H.M. and Abdulla, M.A. (2015) Synthesis, characterization and apoptotic activity of quinazolinone Schiff base derivatives toward MCF-7 cells via intrinsic and extrinsic apoptosis pathways. Scientific Reports, 5 (1). p. 11544. ISSN 2045-2322

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Official URL: http://dx.doi.org/10.1038/srep11544

Abstract

The current study investigated the cytotoxic effect of 3-(5-chloro-2-hydroxybenzylideneamino)-2-(5-chloro-2-hydroxyphenyl)-2,3-dihydroquinazolin-41(H)-one (A) and 3-(5-nitro-2-hydroxybenzylideneamino)-2-(5-nitro-2-hydroxyphenyl)-2,3-dihydroquinazolin-4(1H)-one (B) on MCF-7, MDA-MB-231, MCF-10A and WRL-68 cells. The mechanism involved in apoptosis was assessed to evaluate the possible pathways induced by compound A and B. MTT assay results using A and B showed significant inhibition of MCF-7 cell viability, with IC 50 values of 3.27±0.171 and 4.36±0.219μg/mL, respectively, after a 72hour treatment period. Compound A and B did not demonstrate significant cytotoxic effects towards MDA-MB-231, WRL-68 and MCF-10A cells. Acute toxicity tests also revealed an absence of toxic effects on mice. Fluorescent microscopic studies confirmed distinct morphological changes (membrane blebbing and chromosome condensation) corresponding to typical apoptotic features in treated MCF-7 cells. Using Cellomics High Content Screening (HCS), we found that compound A and B could trigger the release of cytochrome c from mitochondria to the cytosol. The release of cytochrome c activated the expression of caspases-9 and then stimulated downstream executioner caspase-3/7. In addition, caspase-8 showed remarkable activity, followed by inhibition of NF-κ B activation in A-and B-treated MCF-7 cells. The results indicated that A and B could induce apoptosis via a mechanism that involves either extrinsic or intrinsic pathways.

Item Type: Article
Uncontrolled Keywords: Apoptosis; Caspase 3; Caspase 7; Caspase 8; Caspase 9; Cell Line, Tumor; Cell Survival; Crystallography, X-Ray; Cytochromes c; Humans; Hydrazones; Magnetic Resonance Spectroscopy; MCF-7 Cells; Membrane Potential, Mitochondrial; Microscopy, Fluorescence; Mitochondria; Molecular Conformation; NF-kappa B; Quinazolinones; Reactive Oxygen Species; Schiff Bases
Subjects: Q Science > Q Science (General)
R Medicine
Divisions: Faculty of Medicine
Faculty of Science
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 20 Sep 2018 04:19
Last Modified: 20 Sep 2018 04:19
URI: http://eprints.um.edu.my/id/eprint/19315

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