Achillea fragrantissima (Forssk.) Sch.Bip Flower Dichloromethane Extract Exerts Anti-Proliferative and Pro-Apoptotic Properties in Human Triple-Negative Breast Cancer (MDA-MB-231) Cells: In Vitro and In Silico Studies

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 (IC50) 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 IC50 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.

Apoptotic and anti-migratory effects of <i>Achillea millefolium</i> dichloromethane extract on MDA-MB-231 human breast cancer cells

“…In the present study, the IC 50 value of the AMDF was found to be within this specified range, categorising it as a promising extract. Consistent with our findings, Alshuail et al (2022) demonstrated that the dichloromethane fraction of A. fragrantissima was the most effective fraction against MDA-MB-231, as indicated by the half-inhibitory concentration values (Alshuail et al, 2022). Furthermore, a recent study by Mohammed et al (2023) showed that the n-hexane fraction of A. millefolium exhibited moderate cytotoxicity (IC 50 > 100 µg/ml) against MCF-7 breast cancer cells (Mohammed et al, 2023).…”

Achillea fragrantissima (Forssk.) Sch.Bip instigates the ROS/FADD/c-PARP expression that triggers apoptosis in breast cancer cell (MCF-7)

“…Aerial parts of this achillea were used in folk medicine in Saudi Arabia, followed by the historical hero Achilles during the A.fragrantissima Trojan war period [11]. Various studies have been performed, and it illustrates that medicinal properties such as anti-neuroinflammatory [17], anti-angiogenesis [18], anti-metastasis [18], neuroprotection [19], myorelaxant [20], anti-inflammatory [21], anti-diabetic [22,23], anti-trypanosomal [24], anti-microbial [25,26], anti-oxidant [27], anti-proliferation [28], pro-apoptotic [28], cytotoxicity [9,27], and anti-cancer [29][30][31][32][33] effects through the difference solvent extract, prepared oil or phytochemical constituents isolation methods. Despite that, a deep mechanism needs to prove the effect of A.fragrantissima on apoptosis function.…”

Effect of Achillea fragrantissima Extract on Excision Wound Biofilms of MRSA and Pseudomonas aeruginosa in Diabetic Mice

“…Interesting antibiofilm and anti-quorum sensing abilities have been reported in several desert plants, suggesting that these plants possess strong antimicrobial effects [10]. Achillea fragrantissima (yarrow) is commonly known as 'Quysoomaletri' in Arabic and is widely found in Arab countries [11]. It is traditionally used as a medicinal tea for the treatment of various disorders, such as respiratory infections, digestive problems, eye infections, diabetes, and diarrhea [12].…”