In Vitro Cytotoxic Effects and Mechanisms of Action of Eleutherine Isolated from <i>Eleutherine plicata</i> Bulb in Rat Glioma C6 Cells
Victoria Mae Tsuruzaki Shinkai,
Izana Marize Oliveira Sampaio,
Eline Gomes dos Santos,
Adan Jesús Galué-Parra,
Dionisia Pelaes Ferreira,
Drielly Dayanne Monteiro Santos Baliza,
Neidiane Farias Ramos,
Raphael Sanzio Pimenta,
Rommel Mario Rodriguez Burbano,
Chubert Bernardo Castro Sena,
Barbarella Matos Macchi,
Irlon Maciel Ferreira,
Edilene Oliveira Silva,
José Luiz Martins do Nascimento
Affiliations
Victoria Mae Tsuruzaki Shinkai
Programa de Pós-Graduação em Farmacologia e Bioquímica, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belem 66075-110, Brazil
Izana Marize Oliveira Sampaio
Laboratório de Neuroquímica Molecular e Celular, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belem 66075-110, Brazil
Eline Gomes dos Santos
Laboratório de Neuroquímica Molecular e Celular, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belem 66075-110, Brazil
Adan Jesús Galué-Parra
Laboratorio de Biologia Estrutural, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belem 66075-110, Brazil
Dionisia Pelaes Ferreira
Programa de Pós-Graduação em Ciências Farmacêuticas, Departamento de Ciências Biológicas e da Saúde, Universidade Federal do Amapá, Macapa 68902-280, Brazil
Drielly Dayanne Monteiro Santos Baliza
Programa de Pós-Graduação em Biodiversidade e Biotecnologia da Região Norte, Universidade Federal do Tocantins, Palmas 77001-090, Brazil
Neidiane Farias Ramos
Laboratório de Neuroquímica Molecular e Celular, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belem 66075-110, Brazil
Raphael Sanzio Pimenta
Programa de Pós-Graduação em Biodiversidade e Biotecnologia da Região Norte, Universidade Federal do Tocantins, Palmas 77001-090, Brazil
Rommel Mario Rodriguez Burbano
Laboratório de Citogenética Humana, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belem 66075-110, Brazil
Chubert Bernardo Castro Sena
Laboratorio de Biologia Estrutural, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belem 66075-110, Brazil
Barbarella Matos Macchi
Programa de Pós-Graduação em Farmacologia e Bioquímica, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belem 66075-110, Brazil
Irlon Maciel Ferreira
Programa de Pós-Graduação em Ciências Farmacêuticas, Departamento de Ciências Biológicas e da Saúde, Universidade Federal do Amapá, Macapa 68902-280, Brazil
Edilene Oliveira Silva
Laboratorio de Biologia Estrutural, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belem 66075-110, Brazil
José Luiz Martins do Nascimento
Programa de Pós-Graduação em Farmacologia e Bioquímica, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belem 66075-110, Brazil
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.
