Abstract
The aggressive triple-negative breast cancer (TNBC) is a challenging disease due to the absence of tailored therapy. The search for new therapies involves intensive research focusing on natural sources.
Achillea fragrantissima
(
A. fragrantissima
) is a traditional medicine from the Middle East region. Various solvent extracts from different
A. fragrantissima
plant parts, including flowers, leaves, and roots, were tested on TNBC MDA-MB-231 cells. Using liquid chromatography, the fingerprinting revealed rich and diverse compositions for
A. fragrantissima
plant parts using polar to non-polar solvent extracts indicating possible differences in bioactivities. Using the CellTiter-Glo™ viability assay, the half-maximal inhibitory concentration (IC
50
) values were determined for each extract and ranged from 32.4 to 161.7 µg/mL. The
A. fragrantissima
flower dichloromethane extract had the lowest mean IC
50
value and was chosen for further investigation. Upon treatment with increasing
A. fragrantissima
flower dichloromethane extract concentrations, the MDA-MB-231 cells displayed, in a dose-dependent manner, enhanced morphological and biochemical hallmarks of apoptosis, including cell shrinkage, phosphatidylserine exposure, caspase activity, and mitochondrial outer membrane permeabilization, assessed using phase-contrast microscopy, fluorescence-activated single-cell sorting analysis, Image-iT™ live caspase, and mitochondrial transition pore opening activity, respectively. Anticancer target prediction and molecular docking studies revealed the inhibitory activity of a few
A. fragrantissima
flower dichloromethane extract-derived metabolites against carbonic anhydrase IX, an enzyme reported for its anti-apoptotic properties. In conclusion, these findings suggest promising therapeutic values of the
A. fragrantissima
flower dichloromethane extract against TNBC development.