In Vitro Cytotoxic Effects and Mechanisms of Action of Eleutherine Isolated from Eleutherine plicata Bulb in Rat Glioma C6 Cells

Abstract

Gliomas are the most common primary malignant brain tumors in adults, and have a poor prognosis, despite the different types of treatment available. There is growing demand for new therapies to treat this life-threatening tumor. Quinone derivatives from plants have received increased interest as potential anti-glioma drugs, due to their diverse pharmacologic activities, such as inhibiting cell growth, inflammation, tumor invasion, and promoting tumor regression. Previous studies have demonstrated the anti-glioma activity of Eleutherine plicata, which is related to three main naphthoquinone compounds—eleutherine, isoeleutherine, and eleutherol—but their mechanism of action remains elusive. Thus, the aim of this study was to investigate the mechanism of action of eleutherine on rat C6 glioma. In vitro cytotoxicity was evaluated by MTT assay; morphological changes were evaluated by phase-contrast microscopy. Apoptosis was determined by annexin V–FITC–propidium iodide staining, and antiproliferative effects were assessed by wound migration and colony formation assays. Protein kinase B (AKT/pAKT) expression was measured by western blot, and telomerase reverse transcriptase mRNA was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Eleutherine reduced C6 cell proliferation in a dose-dependent manner, suppressed migration and invasion, induced apoptosis, and reduced AKT phosphorylation and telomerase expression. In summary, our results suggest that eleutherine has potential clinical use in treating glioma.

Study of Genotoxicity, Activities on Caspase 8 and on the Stabilization of the Topoisomerase Complex of Isoeleutherin and Analogues

“…These species present high levels of this class of natural products and diverse biological activities. Aqueous extract obtained from dried bulbs of these herbs has been described as generating oxidative stress by inducing the deleterious endogenous formation of a bioactive oxygen-derived species that promotes apoptosis, inhibits inflammation and has important anticancer properties in different cancer cell lineages, such as glioma (U-251), breast (MCF-7), ovary (NCI/ADR-RES), kidney (786-0), non-small cell lung (NCI-H460), colon (HT-29), HepG2 cells and leukemia (K562) [ 11 , 25 ].…”

Participation of Oxidative Stress in the Activity of Compounds Isolated from Eleutherine plicata Herb

“…In a study of the antitumor activity of eleutherine isolated from E. plicata , it was observed that this naphthoquinone had cytotoxic effects capable of reducing the proliferation of C6 cells in a dose-dependent manner, as well as suppressing tumor migration and invasion. Furthermore, it reduced protein kinase B (AKT) phosphorylation and telomerase expression, which results in cell cycle disruption and induces apoptosis in glioma cells [ 10 ].…”