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J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Bacterioruberin (BR), a C50 carotenoid produced by halophilic archaea, is emerging as a bioactive molecule with potential anticancer relevance, but its activity in solid tumour and multidrug-resistant (MDR) models remains poorly defined. This in vitro study evaluated the cytotoxic, antiproliferative and growth-inhibitory effects of a chemically characterized bacterioruberin-rich carotenoid extract (BRCE) from Haloferax (H.) mediterranei in A549 lung adenocarcinoma, BT-549 triple-negative breast cancer and WM115 melanoma cells, as well as in paired sensitive\/multidrug resistant (MDR) lung cancer models. Metabolic activity and proliferation were assessed by thiazolyl blue tetrazolium bromide (MTT) and carboxyfluorescein diacetate succinimidyl ester (CFDA-SE) assays, intracellular reactive oxygen species (ROS) by 2\u2032,7\u2032-dichlorodihydrofluorescein diacetate (H2DCFDA) staining, and apoptosis-associated morphology by acridine orange\/ethidium bromide (AO\/EB) staining. Growth inhibition in A549\/A549-CDR2 and NCI-H460\/NCI-H460\/R cells was analysed by sulforhodamine B (SRB) assay, while P-glycoprotein (P-gp) function and expression were examined using Rhodamine 123 (Rh123) accumulation and Western blotting. BRCE reduced metabolic activity and proliferation in a concentration- and time-dependent manner, increased intracellular ROS levels, and induced apoptosis-associated morphological changes in A549 cells. In MDR models, BRCE retained comparable growth-inhibitory activity in sensitive and resistant cells and partially attenuated P-gp-related drug efflux. These findings support further mechanistic investigation of BR in solid tumour and MDR cancer models.<\/jats:p>","DOI":"10.3390\/ijms27156658","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T09:47:41Z","timestamp":1785145661000},"page":"6658","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bacterioruberin from Haloferax mediterranei Triggers Cytotoxic and Pro-Oxidant Effects in Different Solid Tumour Models, Effectively Targeting P-gp-Resistant Lung Cancer Cells"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3270-307X","authenticated-orcid":false,"given":"Andr\u00e9s","family":"Baeza-Morales","sequence":"first","affiliation":[{"name":"Immunology, Cellular and Developmental Biology Group, Department of Biotechnology, University of Alicante, Ap. 99, E-03080 Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0536-1185","authenticated-orcid":false,"given":"Sandra","family":"Pascual-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Immunology, Cellular and Developmental Biology Group, Department of Biotechnology, University of Alicante, Ap. 99, E-03080 Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4370-5468","authenticated-orcid":false,"given":"Pascual","family":"Mart\u00ednez-Peinado","sequence":"additional","affiliation":[{"name":"Immunology, Cellular and Developmental Biology Group, Department of Biotechnology, University of Alicante, Ap. 99, E-03080 Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Navarro-Sempere","sequence":"additional","affiliation":[{"name":"Immunology, Cellular and Developmental Biology Group, Department of Biotechnology, University of Alicante, Ap. 99, E-03080 Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1727-2603","authenticated-orcid":false,"given":"Yolanda","family":"Segovia","sequence":"additional","affiliation":[{"name":"Immunology, Cellular and Developmental Biology Group, Department of Biotechnology, University of Alicante, Ap. 99, E-03080 Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1924-8729","authenticated-orcid":false,"given":"Miguel","family":"Medina-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Immunology, Cellular and Developmental Biology Group, Department of Biotechnology, University of Alicante, Ap. 99, E-03080 Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Pujalte-Satorre","sequence":"additional","affiliation":[{"name":"Immunology, Cellular and Developmental Biology Group, Department of Biotechnology, University of Alicante, Ap. 99, E-03080 Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5491-0770","authenticated-orcid":false,"given":"R\u00faben","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Faculty of Medicine of the University of Porto (FMUP), 4200-319 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6823-4781","authenticated-orcid":false,"given":"Magdalena","family":"Garc\u00eda","sequence":"additional","affiliation":[{"name":"Immunology, Cellular and Developmental Biology Group, Department of Biotechnology, University of Alicante, Ap. 99, E-03080 Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2679-135X","authenticated-orcid":false,"given":"Rosa Mar\u00eda","family":"Mart\u00ednez-Espinosa","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Biology and Edaphology and Agricultural Chemistry Department, Faculty of Sciences, University of Alicante, Ap. 99, E-03080 Alicante, Spain"},{"name":"Applied Biochemistry Research Group, Multidisciplinary Institute for Environmental Studies \u201cRam\u00f3n Margalef\u201d, University of Alicante, Ap. 99, E-03080 Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7801-4643","authenticated-orcid":false,"given":"M. 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