Prevention of DMBA-induced mammary gland tumors in mice by a dual-function inhibitor of JAK3 and EGF receptor tyrosine kinases

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dc.authoridSahin, Taha Koray/0000-0002-3590-0426
dc.authoridOrhan, Cemal/0000-0003-4138-7689
dc.authoridYabas, Mehmet/0000-0002-3462-5389
dc.authoridŞAHİN, KAZIM/0000-0002-6459-1853
dc.authoridSahin, Kazim/0000-0001-9542-5244
dc.authoridÖZERCAN, ibrahim Hanifi/0000-0002-8781-8838
dc.authoridTuzcu, Mehmet/0000-0002-1329-3143
dc.authorwosidSahin, Taha Koray/ABH-1748-2020
dc.authorwosidOrhan, Cemal/Q-2086-2015
dc.authorwosidYabas, Mehmet/D-9513-2012
dc.authorwosidŞAHİN, KAZIM/AAG-2742-2019
dc.authorwosidSahin, Kazim/D-5625-2009
dc.authorwosidÖZERCAN, ibrahim Hanifi/W-7883-2018
dc.authorwosidTuzcu, Mehmet/H-2953-2018
dc.contributor.authorSahin, Kazim
dc.contributor.authorYabas, Mehmet
dc.contributor.authorOrhan, Cemal
dc.contributor.authorTuzcu, Mehmet
dc.contributor.authorSahin, Taha K.
dc.contributor.authorOzercan, Ibrahim H.
dc.contributor.authorQazi, Sanjive
dc.date.accessioned2024-06-12T10:55:13Z
dc.date.available2024-06-12T10:55:13Z
dc.date.issued2020
dc.departmentTrakya Üniversitesien_US
dc.description.abstractObjectives: We tested the chemopreventive effect of WHI-P131 in side by side evaluation with the standard anti-breast cancer drug paclitaxel in the well-established 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast cancer model. Methods: One hundred BALB/cmice were divided into five groups. (i) Control (ii) DMBA (iii) DMBA+ Paclitaxel (10 mg/kg) (iv) DMBA+WHI-P131 (Janex1, 50 mg/kg of BW, i.p, three times per week) (J) (v) DMBA+P+J. The duration of study was 25 weeks. Results: Our findings demonstrate that WHI-P131 impedes DMBA-induced carcinogenesis, reduces size, weight, and load of tumors (P < 0.001) in DMBA-challenged mice and improves their survival outcome (P < 0.01). The tumors developing despite WHI-P131 chemoprevention displayedattenuated levels of JAK3, STAT3, and NF-kappa B as well as increased I-kappa B expression (P < 0.001). Notably, these tumors exhibited significantly decreased levels of phosphorylated AKT-PI3-Kinase pathway signaling proteins p-mTOR, p-p70S6K1, and p-4E-BP1 (P < 0.001). Our findings are consistent with a model in which DMBA-induced malignant clones with low-level expression of the six signature proteins JAK3/STAT3/NF-kappa B/p-mTOR, p-p70S6K1/p-4E-BP1, albeit not as aggressive as their JAK3/STAT3/NF-kappa B overexpressing counterparts are capable of escaping chemo-preventive effects of WHI-P131. Conclusion: These insights may provide the foundation for new chemo-preventive strategies in which WHI-P131 is applied to prevent the development of aggressive forms of breast cancer.en_US
dc.description.sponsorshipDivision of Cancer Prevention, National Cancer Institute (NIH DHHS), USA [U01-CA-151837]; Turkish Academy of Sciences, Turkeyen_US
dc.description.sponsorshipThe work of the authors was funded by Division of Cancer Prevention, National Cancer Institute (NIH DHHS grant U01-CA-151837), USA and Turkish Academy of Sciences, Turkey. The funders had no role in the paper design, data collection, data analysis, interpretation, writing of the paper.en_US
dc.identifier.doi10.1080/14728222.2020.1737014
dc.identifier.endpage387en_US
dc.identifier.issn1472-8222
dc.identifier.issn1744-7631
dc.identifier.issue4en_US
dc.identifier.pmid32106727en_US
dc.identifier.scopus2-s2.0-85080886071en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage379en_US
dc.identifier.urihttps://doi.org/10.1080/14728222.2020.1737014
dc.identifier.urihttps://hdl.handle.net/20.500.14551/19340
dc.identifier.volume24en_US
dc.identifier.wosWOS:000518292300001en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherTaylor & Francis Ltden_US
dc.relation.ispartofExpert Opinion On Therapeutic Targetsen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectBreast Canceren_US
dc.subjectJAK3 Inhibitoren_US
dc.subjectMiceen_US
dc.subjectPaclitaxelen_US
dc.subjectWhi-P131en_US
dc.subjectEpidermal-Growth-Factoren_US
dc.subjectTargeting Janus Kinase-3en_US
dc.subjectVersus-Host-Diseaseen_US
dc.subjectBreast-Canceren_US
dc.subjectSignaling Pathwayen_US
dc.subjectPharmacokinetic Featuresen_US
dc.subjectWhi-P131en_US
dc.subjectCellsen_US
dc.subjectStatisticsen_US
dc.subjectExpressionen_US
dc.titlePrevention of DMBA-induced mammary gland tumors in mice by a dual-function inhibitor of JAK3 and EGF receptor tyrosine kinasesen_US
dc.typeArticleen_US

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