Abstract
BACKGROUND: Carvacrol, a natural phenolic monoterpenoid, has been suggested to exert anticancer effects; however, its underlying mechanisms in breast cancer (BC) remain incompletely defined. METHODS: MCF-7 (HR(+)) and MDA-MB-231 (TNBC) BC cell lines were treated with carvacrol at various concentrations. Cell viability was assessed using CVDK8 kit, while migration was evaluated by wound healing assays. Apoptosis was determined using Annexin V-FITC Kit, and ROS levels were measured by DCFH-DA assay. Flow cytometry was used for CD44/CD133 cancer stem cells markers analysis, and genes expression were quantified using qPCR. RESULTS: Carvacrol significantly inhibited cell proliferation, and migration in both HR(+) and TNBC cells. Additionally, carvacrol increased the BAX/BCL2 ratio, induced apoptosis, and decreased ROS levels, with greater antioxidant activity observed in MCF-7 cells. Moreover, carvacrol suppressed CD44(+) levels, whereas CD133(+) levels were not affected. Gene expression analysis revealed subtype-specific effects where ABCG2 was upregulated in MCF-7 cells but downregulated in MDA-MB-231 cells, while NF(K)B1 expression increased in both lines. CONCLUSIONS: Carvacrol exerts multitargeted anticancer effects in BC by promoting apoptosis, reducing ROS, and suppressing CD44(+), with distinct subtype-specific responses. These findings highlight carvacrol as a promising natural therapeutic compound for BC treatment; however, further in vivo studies and clinical investigations are required to validate its translational potential.