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 derivativesAuthor | |||||
Journal series | Current Cancer Drug Targets, ISSN 1568-0096, (A 35 pkt) | ||||
Issue year | 2018 | ||||
Vol | 18 | ||||
No | 7 | ||||
Pages | 706-717 | ||||
Publication size in sheets | 0.55 | ||||
Keywords in English | Anticanceragent,stilbene,oxepin,apoptosis,cellcycle arrest,EUFA30,HEK293,HeLa,U87 | ||||
ASJC Classification | ; ; | ||||
DOI | DOI:10.2174/1568009617666170623120742 | ||||
URL | https://www.ncbi.nlm.nih.gov/pubmed/28669347 | ||||
Language | en angielski | ||||
File |
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Score (nominal) | 35 | ||||
Score | = 35.0, 23-09-2019, ArticleFromJournal | ||||
Publication indicators | : 2017 = 0.6; : 2017 = 2.626 (2) - 2017=3.186 (5); = 1 | ||||
Citation count* |
* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.
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