{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T10:13:29Z","timestamp":1779963209094,"version":"3.53.1"},"update-to":[{"DOI":"10.14712\/fb2026.0006","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T00:00:00Z","timestamp":1778457600000}},{"DOI":"10.14712\/fb2026.0006","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000}}],"reference-count":26,"publisher":"Charles University in Prague, Karolinum Press","issue":"2","license":[{"start":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T00:00:00Z","timestamp":1776384000000},"content-version":"vor","delay-in-days":106,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T00:00:00Z","timestamp":1776384000000},"content-version":"tdm","delay-in-days":106,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002679","name":"Adnan Menderes \u00dcniversitesi","doi-asserted-by":"publisher","award":["TPF-21012"],"award-info":[{"award-number":["TPF-21012"]}],"id":[{"id":"10.13039\/501100002679","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["foliabiologica.lf1.cuni.cz"],"crossmark-restriction":true},"short-container-title":["Fol. Biol."],"published-print":{"date-parts":[[2026]]},"abstract":"<jats:p>Cyclin-dependent kinase 4\/6 (CDK4\/6) inhibitors such as palbociclib have improved the treatment of hormone receptor-positive, luminal A breast cancer; however, therapeutic resistance remains a major challenge. Wild-type p53-induced phosphatase 1 (Wip1) is a negative regulator of the p53 pathway and is often over-expressed in luminal breast cancers. This study aimed to determine whether Wip1 inhibition enhances the anti-proliferative and pro-apoptotic effects of the CDK4\/6 inhibitor palbociclib in luminal A breast cancer cells and to elucidate the underlying cell cycle-related mechanisms. MCF-7 cells were treated with palbociclib and Wip1 inhibitor GSK2830371, alone or in combination. Cell viability was assessed using the WST-1 assay, cell cycle distribution was analysed by flow cytometry, and apoptosis was evaluated using Annexin V\/7-aminoactinomycin D staining. Expression of cell cycle regulators (CDK2, CDK4, CDK6, cyclin D1\/D3, Rb, phospho-Rb) and p53-related proteins (p53, phospho-p53 Ser15, p21, p27) was determined by Western blot analysis. The combined treatment produced a concentration-dependent reduction in cell viability and a marked increase in both early and late apoptotic populations compared with monotherapies. While palbociclib alone induced G1 arrest, co-treatment with GSK2830371 shifted cells toward G2 accumulation. This was accompanied by enhanced phosphorylation of p53, up-regulation of p21 and p27, and dephosphorylation of Rb, indicating dual checkpoint engagement. These findings demonstrate that Wip1 inhibition augments palbociclib-mediated cell cycle arrest and apoptosis through modulation of the p53-Rb axis. The dual blockade of Wip1 and CDK4\/6 may represent a promising therapeutic strategy for p53-proficient luminal A breast cancer.<\/jats:p>","DOI":"10.14712\/fb2026.0006","type":"journal-article","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T09:57:37Z","timestamp":1776419857000},"page":"59-67","update-policy":"https:\/\/doi.org\/10.14712\/crossmark-policy-fb","source":"Crossref","is-referenced-by-count":0,"title":["Wip1 Inhibition Enhances the Therapeutic Efficacy of Palbociclib in Luminal A Breast Cancer by Modulating Cell Cycle Progression and Apoptosis"],"prefix":"10.14712","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3802-461X","authenticated-orcid":false,"given":"G\u00f6khan","family":"\u00c7olak","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0442-1246","authenticated-orcid":false,"given":"Nazllcan","family":"Kaygusuz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4100-5804","authenticated-orcid":false,"given":"Nezih","family":"Meydan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5974-6339","authenticated-orcid":false,"given":"Esin","family":"Oktay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3811-9819","authenticated-orcid":false,"given":"Mehtap","family":"K\u0131l\u0131c Eren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"5727","published-online":{"date-parts":[[2026,4,17]]},"reference":[{"key":"fb2026.0006_1","doi-asserted-by":"crossref","first-page":"5388","DOI":"10.3390\/cancers14215388","volume":"14","author":"Abdelmalak","year":"2022","journal-title":"Cancers (Basel)"},{"key":"fb2026.0006_2","doi-asserted-by":"crossref","first-page":"101235","DOI":"10.1016\/j.currproblcancer.2025.101235","volume":"58","author":"Ambere","year":"2025","journal-title":"\u201d Curr. 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