{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T21:22:25Z","timestamp":1788902545359,"version":"build-2803163510"},"reference-count":49,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T00:00:00Z","timestamp":1758153600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Scientific Research Projects Coordination Unit of Gazi University","award":["TCD-2022-7970"],"award-info":[{"award-number":["TCD-2022-7970"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Supportive agents, such as vitamin B12 (cobalamin, B12) and granulocyte colony-stimulating factor (G-CSF), are widely used during chemotherapy; however, their direct effects on tumor biology are not well understood. We evaluated the impact of pharmacological B12 and G-CSF, alone or in combination with cisplatin, on hormone receptor-positive (MCF-7) and triple-negative (MDA-MB-231) breast cancer cells, conducting in vitro assays of cell viability, cytotoxicity, caspase activation, mitochondrial membrane potential, and cytolytic protein expression. Neither B12 nor G-CSF alone induced cytotoxicity; instead, both promoted proliferation in a dose- and time-dependent manner. When combined with cisplatin, they consistently attenuated drug-induced cytotoxicity, suppressed caspase-3\/-8\/-9 activation, preserved mitochondrial integrity, and reduced perforin\/granzyme expression, exhibiting stronger effects in MCF-7 cells. G-CSF markedly increased proliferation (&gt;130% at 50 ng\/mL), while B12 modestly enhanced viability and mitigated cisplatin-induced damage, particularly in triple-negative cells. These findings indicate that B12 and G-CSF can impair cisplatin efficacy by blunting apoptotic signaling and mitochondrial injury in different breast cancer subtypes. These preclinical findings warrant prospective, biomarker-driven in vivo and clinical studies to delineate the clinical contexts in which B12 and G-CSF can be safely integrated into supportive care without compromising antitumor efficacy.<\/jats:p>","DOI":"10.3390\/ijms26189086","type":"journal-article","created":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T12:54:26Z","timestamp":1758200066000},"page":"9086","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The Responsiveness of Breast Cancer Cells to Varied Levels of Vitamin B12, Cisplatin, and G-CSF"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5685-3748","authenticated-orcid":false,"given":"Volkan","family":"Aslan","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Gazi University, 06560 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duygu Deniz","family":"Usta","sequence":"additional","affiliation":[{"name":"Department of Medical Biology and Genetics, Faculty of Medicine, Gazi University, 06560 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atiye Seda","family":"Yar Sa\u011flam","sequence":"additional","affiliation":[{"name":"Department of Medical Biology and Genetics, Faculty of Medicine, Gazi University, 06560 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmet","family":"\u00d6zet","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Gazi University, 06560 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3835-2741","authenticated-orcid":false,"given":"Osman","family":"S\u00fctc\u00fcoglu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Gazi University, 06560 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K\u00fcr\u015fat","family":"Dikmen","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Faculty of Medicine, Gazi University, 06560 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuriye","family":"\u00d6zdemir","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Gazi University, 06560 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17040","DOI":"10.1038\/nrdp.2017.40","article-title":"Vitamin B12 deficiency","volume":"3","author":"Green","year":"2017","journal-title":"Nat. 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