Carotenoid‐Rich Pigment Extract From Micrococcus terreus SK34 Induces Apoptosis in SH‐SY5Y Neuroblastoma Cells: Integrated Metabolomic, Molecular Docking, and Experimental Validation

ABSTRACT Bacteria‐derived carotenoids have attracted increasing attention as natural bioactive compounds with potential pharmaceutical applications, particularly in cancer therapy. However, the chemical composition and anticancer mechanisms of carotenoids from Micrococcus terreus remain largely unexplored. This study aimed to characterize the carotenoid extract from the locally isolated M. terreus SK34 strain (GenBank: PX765938) and to investigate its anticancer activity and underlying mechanisms using integrated in vitro and in silico approaches. Under nonoptimized culture conditions, strain SK34 produced 128 mg/L of carotenoid‐rich pigment extract. LC‐Q‐TOF‐MS analysis identified eight carotenoids, including phytoene, β‐carotene, astaxanthin, zeaxanthin, β‐cryptoxanthin, α‐carotene, lycopene, and sarcinaxanthin. The extract exerted selective cytotoxicity against different cancer cell lines (IC 50 = 61.91–243.76 μg/mL), particularly the neuroblastoma (SH‐SY5Y) cancer cell line, while showing minimal cytotoxicity toward normal human dermal fibroblasts. Gene expression analysis demonstrated the significant upregulation of proapoptotic genes (p53, BAX, CASP3, CASP8, and CASP9) in the SH‐SY5Y cell line, together with the downregulation of antiapoptotic genes (BCL‐2 and AKT1), whereas autophagy‐related genes were not significantly affected. ELISA and flow cytometry analyses further confirmed apoptosis in the SH‐SY5Y cell line. Molecular docking analyses revealed that β‐carotene, astaxanthin, and zeaxanthin exhibited strong binding affinities toward apoptosis‐related proteins, supporting the experimental findings. This study provides the first comprehensive characterization of carotenoids from M. terreus SK34 and highlights their potential as selective apoptosis‐inducing agents for future anticancer therapy.