Abstract
Among the hundreds of reported Achillea species, A. membranacea (Labill.) DC. is one of the six that grow in Jordan. Many species of this genus are used in folk medicine to treat a variety of ailments and several biological and pharmacological activities have been ascribed to their essential oil (EO). For this study, the EO obtained from a specimen of A. membranacea grown in Jordan was analyzed by GC-MS. Ninety-six compounds were detected, of which oxygenated monoterpenes was the predominant class (47.9%), followed by non-terpene derivatives (27.9%), while sesquiterpenes represented 14.2% of the total composition. The most abundant compound in the EO was 1,8-cineole (21.7%). The cytotoxic activity of the EO was evaluated against three cancer cell lines (MCF7, A2780 and HT29), and one normal fibroblast cell line (MRC5) by MTT assay. Significant growth inhibition was observed in EO-exposed A2780 and HT29 cells (IC50 = 12.99 and 14.02 μg/mL, respectively), while MCF7 and MRC5 were less susceptible. The EO induced apoptosis and increased the preG1 events in A2780 cells. 1,8-Cineole, the major constituent of the EO, exhibited submicromolar cytotoxicity against A2780 cells, and was 42 times more selective against MRC5 cells. Its cytotoxicity against A2780 cells was comparable with that of doxorubicin, but 1,8-cineole was more selective for MRC5 normal cells. Interestingly, 1,8-cineole enhanced apoptosis in A2780, and caused a remarkable dose-dependent increase in preG1 events. Thus, 1,8-cineole has demonstrated promising cytotoxic and proapoptotic properties.
Highlights
Medicinal plants and their constituents have countless biological properties, based mainly on their ability to interact with key enzymes linked to several ailments, including: cancer, diabetes, inflammation, hypertension and Alzheimer’s disease [1,2,3,4,5]
Over 45% of the total was constituted by oxygenated monoterpenes, of which 1,8-cineole was the most represented: exhibiting a relative abundance of 21.7%, it was the most abundant compound in the essential oil (EO)
The major component, 1,8-cineole, was selected for further cytotoxicity assessments. 1,8-Cineole showed remarkable cytotoxicity compared to A. membranacea EO in A2780 cells (0.26 μM); its selectivity was 42 times higher for A2780 compared to MRC5 cells (10.5 μM)
Summary
Medicinal plants and their constituents have countless biological properties, based mainly on their ability to interact with key enzymes linked to several ailments, including: cancer, diabetes, inflammation, hypertension and Alzheimer’s disease [1,2,3,4,5]. The use of the inflorescence, as well as the whole plant, of many of these species has a long-established role in folk medicine to treat a wide range of ailments that mainly affect the digestive system It takes various application forms, which differ depending on the geographical area [10,11,12,13]. Anticancer and cytotoxic effects were reported for the extracts of some Achillea species, including A. clavennae L. and A. millefolium L., the iso-seco-guaianolide, which was isolated from A. clavennae L., exhibited potent antiproliferative and apoptotic effects on U251 and glioma cell lines, with a potency comparable to that of cisplatin [21], mediated by its oxidative and mitotic activities. Beside the EO, we have tested the cytotoxicity, induction of apoptosis and cell cycle effect of its major constituent, 1,8-cineole, against A2780 cell line, disclosing the possible action mechanism of the EO and its major constituent
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