Anticancer Effects of the Organosilicon Multidrug Resistance Modulator SILA 421

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dc.contributor.authorOlszewski, Ulrike
dc.contributor.authorZeillinger, Robert
dc.contributor.authorKars, Meltem Demirel
dc.contributor.authorZalatnai, Attila
dc.contributor.authorMolnar, Jozsef
dc.contributor.authorHamilton, Gerhard
dc.date.accessioned2020-03-26T18:23:54Z
dc.date.available2020-03-26T18:23:54Z
dc.date.issued2012
dc.departmentSelçuk Üniversitesien_US
dc.description.abstract1,3-dimethyl-1,3-bis(4-fluorophenyl)-1,3-bis{3-[1(4-butylpiperazinyl)]-propyl}-disiloxan-tetrahydrochlorid (SILA 421) is a compound that was developed as modulator of the ABC cassette transporter P-glycoprotein. Furthermore, it exerted antimicrobial toxicity, vascular effects, downregulation of chaperone induction and plasmid curing in bacterial cells. Here, this drug was found to possess cytotoxic activity against a panel of human cancer cell lines that do not overexpress P-gp, with 50% inhibitory concentrations ranging between 1.75 +/- 0.38 mu M for GLC14 small cell lung cancer and 34.00 +/- 4.75 mu M for PC-3 prostate cancer cells. HL-60 leukemia and MDA-MB-435 breast cancer cells exhibited cell cycle arrest and apoptotic cell death in response to SILA 421. Assessment of global gene expression of SILA 421-treated HL-60 cells was employed to identify cellular pathways affected by the compound and revealed disturbance of DNA replication, transcription and production of apparently misfolded proteins. Endoplasmatic reticulum stress and downregulation of cell cycle, cellular repair mechanisms and growth factor-related signaling cascades eventually resulted in induction of apoptosis in this cell line. In addition to the well established P-gp inhibitory effect of SILA compounds, reversal of resistance to taxanes, which had been reported for SILA 421 and the related molecule SILA 409, may be linked to downregulation of gene expression of kinesins. Interference with DNA replication and transcription seems to be the common denominator of antimicrobial activity and plasmid curing, as well as anticancer toxicity in human cell lines. Thus, in consideration of the full range of putative cellular targets found in the present work, the application of these SILA compounds for treatment of tumors should be further evaluated.en_US
dc.description.sponsorshipFoundation for Cancer Research, Szeged, Hungaryen_US
dc.description.sponsorshipThis work was in part supported by The Foundation for Cancer Research, Szeged, Hungary. The authors declare that they have no conflict of interest.en_US
dc.identifier.doi10.2174/187152012800617777en_US
dc.identifier.endpage671en_US
dc.identifier.issn1871-5206en_US
dc.identifier.issn1875-5992en_US
dc.identifier.issue6en_US
dc.identifier.pmid22263791en_US
dc.identifier.scopusqualityQ3en_US
dc.identifier.startpage663en_US
dc.identifier.urihttps://dx.doi.org/10.2174/187152012800617777
dc.identifier.urihttps://hdl.handle.net/20.500.12395/27751
dc.identifier.volume12en_US
dc.identifier.wosWOS:000309069000009en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherBENTHAM SCIENCE PUBL LTDen_US
dc.relation.ispartofANTI-CANCER AGENTS IN MEDICINAL CHEMISTRYen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.selcuk20240510_oaigen_US
dc.subjectAnnexin Ven_US
dc.subjectCell linesen_US
dc.subjectCellular pathwaysen_US
dc.subjectCytotoxicityen_US
dc.subjectDrug resistanceen_US
dc.subjectGene expressionen_US
dc.subjectHL-60en_US
dc.subjectMDR modulatoren_US
dc.subjectOrganosiliconen_US
dc.subjectP-glycoproteinen_US
dc.subjectPhenothiazineen_US
dc.subjectReactomeen_US
dc.subjectSILA 421en_US
dc.titleAnticancer Effects of the Organosilicon Multidrug Resistance Modulator SILA 421en_US
dc.typeArticleen_US

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