Achillea millefolium L. hydroethanolic extract inhibits growth of human tumor cell lines by interfering with cell cycle and inducing apoptosis

Abstract

The cell growth inhibitory activity of the hydroethanolic extract of Achillea millefolium was studied in human tumor cell lines (NCI-H460 and HCT-15) and its mechanism of action was investigated. The GI concentration was determined with the sulforhodamine B assay and cell cycle and apoptosis were analyzed by flow cytometry following incubation with PI or Annexin V FITC/PI, respectively. The expression levels of proteins involved in cell cycle and apoptosis were analyzed by Western blot. The extracts were characterized regarding their phenolic composition by LC-DAD-ESI/MS. 3,5-O-Dicaffeoylquinic acid, followed by 5-O-caffeoylquinic acid, were the main phenolic acids, while, luteolin-O-acetylhexoside and apigenin-O-acetylhexoside were the main flavonoids. This extract decreased the growth of the tested cell lines, being more potent in HCT-15 and then in NCI-H460 cells. Two different concentrations of the extract (75 and 100 μg/mL) caused alterations in cell cycle profile and increased apoptosis levels in HCT-15 and NCI-H460 cells. Moreover, the extract caused an increase in p53 and p21 expression in NCI-H460 cells (which have wt p53), and reduced XIAP levels in HCT-15 cells (with mutant p53). This work enhances the importance of A. millefolium as source of bioactive phenolic compounds, particularly of XIAP inhibitors.

Proapoptotic Activity of Achillea membranacea Essential Oil and Its Major Constituent 1,8-Cineole against A2780 Ovarian Cancer Cells

“…Furthermore, the cell cycle perturbation results of the present work were similar to those observed in a previous study conducted on wild-type p53 H460 cells (but not mutant p53 H460 cells) after the treatment with Achillea millefolium hydroalcoholic extract [39]. Pereira et al (2018) demonstrated the induction of apoptosis and S-phase arrest, with an increased level of p53 and p21 indicating the different mechanisms involved in the Achillea millefolium extract-induced growth arrest. Likewise, a previous study reported that casticin, a flavonoid extracted from Achillea millefolium, caused G 2 /M arrest in HCT116 colon cancer cells, which was confirmed by the induction of p21 and down-regulation of CDK1 [14].…”

Eucalyptus globulus Labill. decoction extract inhibits the growth of NCI-H460 cells by increasing the p53 levels and altering the cell cycle profile

“…Given this problematic issue, the screening of natural compounds as potential anti-tumor agents has become an interesting approach worldwide. [7][8][9][10][11][12] Most notably, nearly half of the small molecules approved for cancer treatment were either actually natural products or derived from such products. 13 Some of the most relevant anticancer drugs in this category include frequently used agents such as Taxol, vinblastine and camptothecin.…”

Pharmacology Evaluation of Bioactive Compounds that Regulate Cervical Cancer Cells

“…But, reducing the doses of the chemical agent or employing natural compounds can overcome this significant barrier that exists to eliminate CC [11]. Natural or bioactive compounds are used against multiple illnesses including rheumatic, anthelmintic, diuretic, hypoglycaemia and cancer [23].…”