{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T13:34:29Z","timestamp":1775136869175,"version":"3.50.1"},"reference-count":54,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2019,7,26]],"date-time":"2019-07-26T00:00:00Z","timestamp":1564099200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010621","name":"Medical University of Lublin","doi-asserted-by":"publisher","award":["DS440\/2018-2019"],"award-info":[{"award-number":["DS440\/2018-2019"]}],"id":[{"id":"10.13039\/501100010621","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Polish Ministry of Science and Higher Education","award":["MNmb 510\/2016-2017"],"award-info":[{"award-number":["MNmb 510\/2016-2017"]}]},{"name":"Polish National Science Centre","award":["DEC-2015\/17\/B\/NZ1\/01777"],"award-info":[{"award-number":["DEC-2015\/17\/B\/NZ1\/01777"]}]},{"name":"Polish National Science Centre","award":["DEC-2017\/25\/B\/NZ4\/02364"],"award-info":[{"award-number":["DEC-2017\/25\/B\/NZ4\/02364"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The aim of this study was to investigate the influence of the Notch1 activity level on the pharmacological interaction between cisplatin (CDDP) and two histone deacetylase inhibitors (HDIs)\u2014valproic acid (VPA) and vorinostat (SAHA) in the triple negative breast cancer (TNBC) cells. Stable breast cancer (BC) cell lines with increased and decreased activity of Notch1 were generated using a transfection method. The type of interaction between CDDP and the HDIs was determined by isobolographic analysis of cell proliferation in MDA-MB-231 cells with differential levels of Notch1 activity in vitro. The combination of CDDP\/SAHA and CDDP\/VPA in the MDA-MB-231 triple negative breast cancer (TNBC) cells with increased activity of Notch1, as well as CDDP\/VPA in the MDA-MB-231 cells with decreased activity of Notch1, yielded an additive interaction, whereas additivity with a tendency towards antagonism was observed for the combination of CDDP\/SAHA in MDA-MB-231 cells with the decreased activity of Notch1. Our studies demonstrated that SAHA and VPA might be considered as potential therapeutic agents in combination therapy with CDDP against TNBC with altered Notch1 activity.<\/jats:p>","DOI":"10.3390\/ijms20153663","type":"journal-article","created":{"date-parts":[[2019,7,26]],"date-time":"2019-07-26T08:45:39Z","timestamp":1564130739000},"page":"3663","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Additive Pharmacological Interaction between Cisplatin (CDDP) and Histone Deacetylase Inhibitors (HDIs) in MDA-MB-231 Triple Negative Breast Cancer (TNBC) Cells with Altered Notch1 Activity\u2014An Isobolographic Analysis"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2388-4577","authenticated-orcid":false,"given":"Anna","family":"Wawruszak","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Medical University of Lublin, Chodzki 1 Street, 20-093 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jarogniew J.","family":"Luszczki","sequence":"additional","affiliation":[{"name":"Isobolographic Analysis Laboratory, Institute of Rural Health, Jaczewskiego 2 Street, 20-090 Lublin, Poland"},{"name":"Department of Pathophysiology, Medical University, Jaczewskiego 8 Street, 20-090 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanna","family":"Kalafut","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Medical University of Lublin, Chodzki 1 Street, 20-093 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7834-7520","authenticated-orcid":false,"given":"Karolina","family":"Okla","sequence":"additional","affiliation":[{"name":"The First Department of Gynecologic Oncology and Gynecology, Medical University of Lublin, Staszica 16 Street, 20-081 Lublin, Poland"},{"name":"Tumor Immunology Laboratory, Medical University of Lublin, Staszica 16 Street, 20-081 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Halasa","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Medical University of Lublin, Chodzki 1 Street, 20-093 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9794-802X","authenticated-orcid":false,"given":"Adolfo","family":"Rivero-Muller","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Medical University of Lublin, Chodzki 1 Street, 20-093 Lublin, Poland"},{"name":"Faculty of Science and Engineering, Cell Biology, Abo Akademi University, Tykistokatu 6A, 20520 Turku, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrzej","family":"Stepulak","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Medical University of Lublin, Chodzki 1 Street, 20-093 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,7,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. 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