In Vitro Cytotoxic Effects and Mechanisms of Action of Eleutherine Isolated from Eleutherine plicata Bulb in Rat Glioma C6 Cells.
Victoria Mae Tsuruzaki ShinkaiIzana Marize Oliveira SampaioEline Gomes Dos SantosAdan Jesús Galué-ParraDionisia Pelaes FerreiraDrielly Dayanne Monteiro Santos BalizaNeidiane Farias RamosRaphael Sanzio PimentaRommel Mario Rodríguez BurbanoChubert Bernardo Castro de SenaBarbarella Matos MacchiIrlon Maciel FerreiraEdilene Oliveira da SilvaJosé Luiz Martins do NascimentoPublished in: Molecules (Basel, Switzerland) (2022)
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.
Keyphrases
- poor prognosis
- induced apoptosis
- oxidative stress
- signaling pathway
- endoplasmic reticulum stress
- cell proliferation
- long non coding rna
- protein kinase
- cell cycle arrest
- high throughput
- pi k akt
- magnetic resonance
- high resolution
- binding protein
- south africa
- high grade
- single molecule
- optical coherence tomography
- risk assessment