Evaluation of Anti-cancer Activity of Stilbene and Methoxydibenzo[b,f]oxepin Derivatives

D. Garbicz , D. Mielecki , M. Wrzesiński , T. Pilżys , M. Marcinkowski , J. Piwowarski , J. Dębski , E. Palak , Przemysław Szczeciński , Hanna Krawczyk , E. Grzesiuk

Abstract

Background: Stilbenes,1,2-diphenylethen derivatives, including resveratrol and combre-tastatins, showanticancer featuresespeciallyagainst tumor angiogenesis. Fosbretabulin, CA-4, in combination with carboplatin,isin the laststagesof clinicaltests asaninhibitor of thyroid cancer. Themode of action of these compoundsinvolves suppression of angiogenesis through interfering with tubulin (de)polymerization. Objective: Wehavepreviously synthesized five E-2-hydroxystilbenes and seven dibenzo [b,f]oxepinsin Zconfiguration,with methylornitro groups atvaried positions.The aimofthepre-sentworkwasto evaluatethe anticancer activity andmolecular mechanism(s)ofactionofthese compounds. Results: Twohealthy,EUFA30 and HEK293, and twocancerous,HeLa and U87, celllineswere treatedwith fournewlysynthetized stilbenes and sevenoxepins.Two of these compounds, JJR5and JJR6, showed the strongest cytotoxic effectagainstcancerous cells tested and these twowere se-lectedfor furtherinvestigations.Theyinduced apoptosiswith sub-G1 orS cellcyclearrest and PARP cleavage,withno visible activationof caspases3and7.Proteomic differential analysisof stilbene-treatedcells led tothe identification ofproteins involvedalmost exclusively in cellcycle management,apoptosis, DNA repairand stressresponse, e.g.oxidative stress. Conclusion: Among the newlysynthesized stilbene derivatives,we selectedtwo aspotent antican-cer compoundstriggering lateapoptosis/necrosisin cancerous cells through sub-G1phasecell cycle arrest.They changed cyclinexpression,induced DNA repairmechanisms,enzymes involved in apoptosisand oxidativestress response.CompoundsJJR5 and JJR6 can be abaseforstructure modification(s)toobtain evenmore active derivatives
Author D. Garbicz
D. Garbicz,,
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, D. Mielecki
D. Mielecki,,
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, M. Wrzesiński
M. Wrzesiński,,
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, T. Pilżys
T. Pilżys,,
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, M. Marcinkowski
M. Marcinkowski,,
-
, J. Piwowarski
J. Piwowarski,,
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, J. Dębski
J. Dębski,,
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, E. Palak
E. Palak,,
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, Przemysław Szczeciński (FC / DOC)
Przemysław Szczeciński,,
- Department Of Organic Chemistry
, Hanna Krawczyk (FC / DOC)
Hanna Krawczyk,,
- Department Of Organic Chemistry
et al.`
Journal seriesCurrent Cancer Drug Targets, ISSN 1568-0096, (A 30 pkt)
Issue year2018
Vol18
No7
Pages706-717
Publication size in sheets0.55
Keywords in EnglishAnticanceragent,stilbene,oxepin,apoptosis,cellcycle arrest,EUFA30,HEK293,HeLa,U87
ASJC Classification1306 Cancer Research; 3002 Drug Discovery; 3004 Pharmacology
DOIDOI:10.2174/1568009617666170623120742
URL https://www.ncbi.nlm.nih.gov/pubmed/28669347
Languageen angielski
File
Current Cancer Drug Targets 18 (2018) 706-717.pdf 2.43 MB
Score (nominal)35
ScoreMinisterial score = 30.0, 11-02-2019, ArticleFromJournal
Ministerial score (2013-2016) = 35.0, 11-02-2019, ArticleFromJournal
Publication indicators Scopus SNIP (Source Normalised Impact per Paper): 2017 = 0.6; WoS Impact Factor: 2017 = 2.626 (2) - 2017=3.186 (5); WoS Citations = 1
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