Cytotoxicity and apoptosis induced by a plumbagin derivative in estrogen positive MCF-7 breast cancer cells
KAUST DepartmentAdvanced Membranes and Porous Materials Research Center
Applied Mathematics and Computational Science Program
Chemical Science Program
Computational Bioscience Research Center (CBRC)
Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division
Physical Science and Engineering (PSE) Division
Smart Hybrid Materials (SHMs) lab
Online Publication Date2014-01-14
Print Publication Date2014-01-31
Permanent link to this recordhttp://hdl.handle.net/10754/325349
MetadataShow full item record
AbstractPlumbagin [5-hydroxy- 2-methyl-1, 4-naphthaquinone] is a well-known plant derived anticancer lead compound. Several efforts have been made to synthesize its analogs and derivatives in order to increase its anticancer potential. In the present study, plumbagin and its five derivatives have been evaluated for their antiproliferative potential in one normal and four human cancer cell lines. Treatment with derivatives resulted in dose- and time-dependent inhibition of growth of various cancer cell lines. Prescreening of compounds led us to focus our further investigations on acetyl plumbagin, which showed remarkably low toxicity towards normal BJ cells and HepG2 cells. The mechanisms of apoptosis induction were determined by APOPercentage staining, caspase-3/7 activation, reactive oxygen species production and cell cycle analysis. The modulation of apoptotic genes (p53, Mdm2, NF-kB, Bad, Bax, Bcl-2 and Casp-7) was also measured using real time PCR. The positive staining using APOPercentage dye, increased caspase-3/7 activity, increased ROS production and enhanced mRNA expression of proapoptotic genes suggested that acetyl plumbagin exhibits anticancer effects on MCF-7 cells through its apoptosis-inducing property. A key highlighting point of the study is low toxicity of acetyl plumbagin towards normal BJ cells and negligible hepatotoxicity (data based on HepG2 cell line). Overall results showed that acetyl plumbagin with reduced toxicity might have the potential to be a new lead molecule for testing against estrogen positive breast cancer. 2014 Bentham Science Publishers.
CitationSagar S, Esau L, Moosa B, Khashab N, Bajic V, et al. (2014) Cytotoxicity and Apoptosis Induced by a Plumbagin Derivative in Estrogen Positive MCF-7 Breast Cancer Cells. Anti-Cancer Agents in Medicinal Chemistry 14: 170-180. doi:10.2174/18715206113136660369.
PublisherBentham Science Publishers Ltd.
PubMed Central IDPMC3894702
CollectionsArticles; Advanced Membranes and Porous Materials Research Center; Applied Mathematics and Computational Science Program; Physical Science and Engineering (PSE) Division; Controlled Release and Delivery Laboratory; Chemical Science Program; Computational Bioscience Research Center (CBRC); Computer, Electrical and Mathematical Science and Engineering (CEMSE) Division
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Except where otherwise noted, this item's license is described as This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.
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