{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T20:18:00Z","timestamp":1769458680768,"version":"3.49.0"},"reference-count":46,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T00:00:00Z","timestamp":1769212800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"publisher","award":["RC-2023-2792851"],"award-info":[{"award-number":["RC-2023-2792851"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Breast cancer is the most frequently diagnosed malignancy among women and is characterized by marked heterogeneity in treatment response. Metabolic reprogramming, particularly enhanced de novo lipogenesis, represents a hallmark of cancer progression and a promising therapeutic target. Firsocostat, a selective allosteric inhibitor of acetyl-CoA carboxylase (ACC), has previously been investigated in metabolic diseases but has never been evaluated in breast cancer models. This study aimed to assess the antitumor effects of firsocostat on breast cancer cell lines. Methods: We investigated the cytotoxic and metabolic effects of firsocostat in four breast cancer cell lines\u2014MCF7 (luminal A HR+), SK-BR-3 (HER2-positive), MDA-MB-231 (triple-negative), and HCC1937 (triple-negative, BRCA1-mutated)\u2014together with the non-tumorigenic MCF-10A line. Dose- and time-dependent responses were evaluated using phase-contrast microscopy for morphological evaluation, Trypan Blue exclusion assays, and MTS-based viability assays. Results: Firsocostat significantly reduced cell viability across all breast cancer subtypes in a concentration- and time-dependent manner, with IC50 values ranging from 80 to 93 \u00b5M. In contrast, non-tumorigenic MCF-10A cells were less affected, indicating a selective cytotoxic effect toward malignant cells. Conclusions: Firsocostat exerts robust cytotoxic effects in breast cancer models, identifying it as a promising metabolism-targeting therapeutic candidate capable of selectively impairing breast cancer cell survival by disrupting fatty acid biosynthesis. These results indicate that firsocostat could represent a viable candidate as a metabolic-based therapeutic approach for breast cancer. Given its established clinical safety profile in metabolic diseases, firsocostat warrants further preclinical investigation and supports further mechanistic and preclinical evaluation.<\/jats:p>","DOI":"10.3390\/ph19020201","type":"journal-article","created":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T10:24:36Z","timestamp":1769423076000},"page":"201","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Antitumor Activity of the ACC Inhibitor Firsocostat in Breast Cancer Cell Lines: A Proof-of-Concept In Vitro Study"],"prefix":"10.3390","volume":"19","author":[{"given":"Simona","family":"Picerno","sequence":"first","affiliation":[{"name":"Laboratory of Preclinical and Translational Research, Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB), Rionero in Vulture, 85028 Potenza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8351-5876","authenticated-orcid":false,"given":"Eugenia","family":"Giglio","sequence":"additional","affiliation":[{"name":"Laboratory of Preclinical and Translational Research, Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB), Rionero in Vulture, 85028 Potenza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7749-8479","authenticated-orcid":false,"given":"Martina","family":"Giuseffi","sequence":"additional","affiliation":[{"name":"Laboratory of Preclinical and Translational Research, Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB), Rionero in Vulture, 85028 Potenza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcello","family":"Radino","sequence":"additional","affiliation":[{"name":"Clinical Analysis Laboratory, Cerba HealthCare Basilicata S.r.l., Rionero in Vulture, 85028 Potenza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3046-7691","authenticated-orcid":false,"given":"Marzia","family":"Sichetti","sequence":"additional","affiliation":[{"name":"Laboratory of Preclinical and Translational Research, Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB), Rionero in Vulture, 85028 Potenza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2100-6981","authenticated-orcid":false,"given":"Marisabel","family":"Mecca","sequence":"additional","affiliation":[{"name":"Laboratory of Preclinical and Translational Research, Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB), Rionero in Vulture, 85028 Potenza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/s41392-024-02108-4","article-title":"Breast cancer: Pathogenesis and treatments","volume":"10","author":"Xiong","year":"2025","journal-title":"Signal Transduct Target Ther."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s40364-024-00631-8","article-title":"Global burden of breast cancer and attributable risk factors in 204 countries and territories, from 1990 to 2021: Results from the Global Burden of Disease Study 2021","volume":"12","author":"Sha","year":"2024","journal-title":"Biomark. 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