Curcumin, a natural compound found in turmeric (Curcuma longa), demonstrates anticancer properties; however, it is characterized by poor bioavailability and stability. This study investigates the stability, antioxidant activity, and anticancer effects of two monocarbonyl analogs of curcumin (MACs), C66 and B2BrBC, in in vitro breast cancer models.

Stability and antioxidant activity of C66 and B2BrBC were assessed using spectrophotometric assays. Their effects on breast cancer cells (MCF-7, BT-474, MDA-MB-231) were evaluated through MTT assay, wound-healing assay, and caspase-3 fluorescence microscopy. EMT modulation was examined via RT-qPCR, Western blot, and immunofluorescence analyses. A MILLIPLEX protein assay was used to analyze cancer metastasis-related protein expression.

C66 and B2BrBC demonstrated enhanced stability compared to curcumin. Both compounds significantly reduced breast cancer cell viability and migration, with B2BrBC showing higher potency. They effectively suppressed EMT, reversing EMT-inducer effects on epithelial and mesenchymal markers. C66 and B2BrBC modulated the expression of several metastasis-related proteins, including DKK1, OPG, and GDF15, in a cell line-dependent manner.

C66 and B2BrBC exhibit improved stability and potent anticancer effects in breast cancer cells, effectively inhibiting cell viability, migration, and EMT. These compounds show promise as potential therapeutic agents for breast cancer, warranting further investigation in in vivo models.