Bacterioruberin from Haloferax mediterranei Triggers Cytotoxic and Pro-Oxidant Effects in Different Solid Tumour Models, Effectively Targeting P-gp-Resistant Lung Cancer Cells

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′,7′-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.