Cytotoxicity and apoptosis induced by a plumbagin derivative in estrogen positive MCF-7 breast cancer cells

Handle URI:
http://hdl.handle.net/10754/325349
Title:
Cytotoxicity and apoptosis induced by a plumbagin derivative in estrogen positive MCF-7 breast cancer cells
Authors:
Sagar, Sunil; Esau, Luke; Moosa, Basem ( 0000-0002-2350-4100 ) ; Khashab, Niveen M. ( 0000-0003-2728-0666 ) ; Bajic, Vladimir B. ( 0000-0001-5435-4750 ) ; Kaur, Mandeep
Abstract:
Plumbagin [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.
KAUST Department:
Computational Bioscience Research Center (CBRC); Smart Hybrid Materials (SHMs) lab
Citation:
Sagar 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.
Publisher:
Bentham Science Publishers
Journal:
Anti-Cancer Agents in Medicinal Chemistry
Issue Date:
31-Jan-2014
DOI:
10.2174/18715206113136660369
PubMed ID:
24164046
PubMed Central ID:
PMC3894702
Type:
Article
ISSN:
18755992
Appears in Collections:
Articles; Controlled Release and Delivery Laboratory; Computational Bioscience Research Center (CBRC)

Full metadata record

DC FieldValue Language
dc.contributor.authorSagar, Sunilen
dc.contributor.authorEsau, Lukeen
dc.contributor.authorMoosa, Basemen
dc.contributor.authorKhashab, Niveen M.en
dc.contributor.authorBajic, Vladimir B.en
dc.contributor.authorKaur, Mandeepen
dc.date.accessioned2014-08-27T09:48:36Z-
dc.date.available2014-08-27T09:48:36Z-
dc.date.issued2014-1-31en
dc.identifier.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.en
dc.identifier.issn18755992en
dc.identifier.pmid24164046en
dc.identifier.doi10.2174/18715206113136660369en
dc.identifier.urihttp://hdl.handle.net/10754/325349en
dc.description.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.en
dc.language.isoenen
dc.publisherBentham Science Publishersen
dc.rightsThis 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.en
dc.rights.urihttp://creativecommons.org/licenses/by-nc/3.0/en
dc.subjectAnticanceren
dc.subjectApoptosisen
dc.subjectBreast canceren
dc.subjectCaspase-3/7en
dc.subjectPlumbaginen
dc.subjectacetyl plumbaginen
dc.subjectbenzoate plumbaginen
dc.subjectcaspase 3en
dc.subjectcaspase 7en
dc.subjectcomplementary DNAen
dc.subjectcrotonate plumbaginen
dc.subjectestrogenen
dc.subjectestrogen receptoren
dc.subjectimmunoglobulin enhancer binding proteinen
dc.subjectisobutyrate plumbaginen
dc.subjectmessenger RNAen
dc.subjectplumbaginen
dc.subjectpropionate plumbaginen
dc.subjectprotein BADen
dc.subjectprotein Baxen
dc.subjectprotein bcl 2en
dc.subjectprotein MDM2en
dc.subjectprotein p53en
dc.subjectreactive oxygen metaboliteen
dc.subjectunclassified drugen
dc.subjectantineoplastic activityen
dc.subjectantiproliferative activityen
dc.subjectAPOPercentage assayen
dc.subjectapoptosisen
dc.subjectbreast canceren
dc.subjectcancer cell cultureen
dc.subjectcancer growthen
dc.subjectcancer inhibitionen
dc.subjectcell cycle parametersen
dc.subjectcontrolled studyen
dc.subjectcytotoxicityen
dc.subjectDNA synthesisen
dc.subjectenzyme activityen
dc.subjectfluorescence activated cell sortingen
dc.subjectgene expressionen
dc.subjecthuman cellen
dc.subjectMCF 7 cell lineen
dc.subjectquantitative assayen
dc.subjectreal time polymerase chain reactionen
dc.subjectRNA extractionen
dc.titleCytotoxicity and apoptosis induced by a plumbagin derivative in estrogen positive MCF-7 breast cancer cellsen
dc.typeArticleen
dc.contributor.departmentComputational Bioscience Research Center (CBRC)en
dc.contributor.departmentSmart Hybrid Materials (SHMs) laben
dc.identifier.journalAnti-Cancer Agents in Medicinal Chemistryen
dc.identifier.pmcidPMC3894702en
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.institutionUnidad Académica de Sistemas Arrecifales (Puerto Morelos), Instituto de Ciencias Del Mar y Limnología, Universidad Nacional Autõnoma de México, Puerto Morelos, QR 77580, Mexicoen
dc.contributor.institutionSchool of Natural Sciences, University of California Merced, 5200 North Lake Road, Merced, CA 95343, United Statesen
dc.contributor.affiliationKing Abdullah University of Science and Technology (KAUST)en
kaust.authorSagar, Sunilen
kaust.authorEsau, Lukeen
kaust.authorMoosa, Basemen
kaust.authorKhashab, Niveen M.en
kaust.authorBajic, Vladimir B.en
kaust.authorKaur, Mandeepen

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