LFM-A13, a potent inhibitor of polo-like kinase, inhibits breast carcinogenesis by suppressing proliferation activity and inducing apoptosis in breast tumors of mice

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dc.authoridOrhan, Cemal/0000-0003-4138-7689
dc.authoridsahin, nurhan/0000-0001-9487-1154
dc.authoridÖZERCAN, ibrahim Hanifi/0000-0002-8781-8838
dc.authoridYabas, Mehmet/0000-0002-3462-5389
dc.authoridSahin, Kazim/0000-0001-9542-5244
dc.authoridTuzcu, Mehmet/0000-0002-1329-3143
dc.authorwosidOrhan, Cemal/Q-2086-2015
dc.authorwosidSahin, Nurhan/D-5626-2009
dc.authorwosidsahin, nurhan/ABF-8007-2020
dc.authorwosidÖZERCAN, ibrahim Hanifi/W-7883-2018
dc.authorwosidYabas, Mehmet/D-9513-2012
dc.authorwosidSahin, Kazim/D-5625-2009
dc.authorwosidTuzcu, Mehmet/H-2953-2018
dc.contributor.authorSahin, Kazim
dc.contributor.authorTuzcu, Mehmet
dc.contributor.authorYabas, Mehmet
dc.contributor.authorOrhan, Cemal
dc.contributor.authorSahin, Nurhan
dc.contributor.authorOzercan, Ibrahim H.
dc.date.accessioned2024-06-12T11:07:38Z
dc.date.available2024-06-12T11:07:38Z
dc.date.issued2018
dc.departmentTrakya Üniversitesien_US
dc.description.abstractThe goals of the present study were to define the anticancer activity of LFM-A13 (alpha-cyano-beta-hydroxy-beta-methyl-N-(2,5-dibromophenyl)-propenamide), a potent inhibitor of Polo-like kinase (PLK), in a mouse mammary cancer model induced by 7,12-dimethylbenz(a)anthracene (DMBA) in vivo and explore its anticancer mechanism(s). We also examined whether the inhibition of PLK by LFM-A13 would improve the efficiency of paclitaxel in breast cancer growth in vivo. To do this, female BALB/c mice received 1 mg of DMBA once a week for 6 weeks with oral gavage. LFM-A13 (50 mg/kg body weight) was administered intraperitoneally with DMBA administration and continued for 25 weeks. We found that LFM-A13, paclitaxel, and their combination have a significant effect on the DMBA-induced breast tumor incidence, mean tumor numbers, average tumor weight, and size. At the molecular level, the administration of LFM-A13 hindered mammary gland carcinoma development by regulating the expression of PLK1, cell cycle-regulating proteins cyclin D1, cyclin dependent kinase-4 (CDK-4), and the CDK inhibitor, p21. Moreover, LFM-A 13 treatment upregulated the levels of I kappa B, the pro-apoptotic proteins Bax, and caspase-3, and down-regulated p53 and the antiapoptotic protein Bcl-2 in mammary tumors. The combination of LFM-A13 with paclitaxel was found to be more effective compared with either agent alone. Collectively, these results suggest that LFM-A13 has an anti-proliferative activity against breast cancer in vivo and that LFM-A13 and paclitaxel combination could be a strategy for the treatment of breast cancer.en_US
dc.description.sponsorshipTurkish Academy of Sciencesen_US
dc.description.sponsorshipThe work was supported in part by the Turkish Academy of Sciences.en_US
dc.identifier.doi10.1007/s10637-017-0540-2
dc.identifier.endpage395en_US
dc.identifier.issn0167-6997
dc.identifier.issn1573-0646
dc.identifier.issue3en_US
dc.identifier.pmid29139009en_US
dc.identifier.scopus2-s2.0-85033722622en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage388en_US
dc.identifier.urihttps://doi.org/10.1007/s10637-017-0540-2
dc.identifier.urihttps://hdl.handle.net/20.500.14551/22117
dc.identifier.volume36en_US
dc.identifier.wosWOS:000431954900004en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherSpringeren_US
dc.relation.ispartofInvestigational New Drugsen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectLFM-A13en_US
dc.subjectMammary Carcinogenesisen_US
dc.subjectPLKen_US
dc.subjectDMBAen_US
dc.subjectCanceren_US
dc.subjectExpressionen_US
dc.subjectPaclitaxelen_US
dc.subjectEfficacyen_US
dc.subjectProfileen_US
dc.subjectTargeten_US
dc.subjectPlk1en_US
dc.subjectP21en_US
dc.subjectPrken_US
dc.subjectBtken_US
dc.titleLFM-A13, a potent inhibitor of polo-like kinase, inhibits breast carcinogenesis by suppressing proliferation activity and inducing apoptosis in breast tumors of miceen_US
dc.typeArticleen_US

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