In Vitro Cytotoxic Effects and Mechanisms of Action of Eleutherine Isolated from <i>Eleutherine plicata</i> Bulb in Rat Glioma C6 Cells
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 pot...
Main Authors: | , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2022-12-01
|
Series: | Molecules |
Subjects: | |
Online Access: | https://www.mdpi.com/1420-3049/27/24/8850 |
_version_ | 1797456048593829888 |
---|---|
author | 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 |
author_facet | 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 |
author_sort | Victoria Mae Tsuruzaki Shinkai |
collection | DOAJ |
description | 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 <i>Eleutherine plicata</i>, 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. |
first_indexed | 2024-03-09T16:02:48Z |
format | Article |
id | doaj.art-f7bf0b7fa50d465a9ea69611c7d8694e |
institution | Directory Open Access Journal |
issn | 1420-3049 |
language | English |
last_indexed | 2024-03-09T16:02:48Z |
publishDate | 2022-12-01 |
publisher | MDPI AG |
record_format | Article |
series | Molecules |
spelling | doaj.art-f7bf0b7fa50d465a9ea69611c7d8694e2023-11-24T16:58:31ZengMDPI AGMolecules1420-30492022-12-012724885010.3390/molecules27248850In Vitro Cytotoxic Effects and Mechanisms of Action of Eleutherine Isolated from <i>Eleutherine plicata</i> Bulb in Rat Glioma C6 CellsVictoria Mae Tsuruzaki Shinkai0Izana Marize Oliveira Sampaio1Eline Gomes dos Santos2Adan Jesús Galué-Parra3Dionisia Pelaes Ferreira4Drielly Dayanne Monteiro Santos Baliza5Neidiane Farias Ramos6Raphael Sanzio Pimenta7Rommel Mario Rodriguez Burbano8Chubert Bernardo Castro Sena9Barbarella Matos Macchi10Irlon Maciel Ferreira11Edilene Oliveira Silva12José Luiz Martins do Nascimento13Programa de Pós-Graduação em Farmacologia e Bioquímica, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belem 66075-110, BrazilLaboratório de Neuroquímica Molecular e Celular, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belem 66075-110, BrazilLaboratório de Neuroquímica Molecular e Celular, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belem 66075-110, BrazilLaboratorio de Biologia Estrutural, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belem 66075-110, BrazilPrograma de Pós-Graduação em Ciências Farmacêuticas, Departamento de Ciências Biológicas e da Saúde, Universidade Federal do Amapá, Macapa 68902-280, BrazilPrograma de Pós-Graduação em Biodiversidade e Biotecnologia da Região Norte, Universidade Federal do Tocantins, Palmas 77001-090, BrazilLaboratório de Neuroquímica Molecular e Celular, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belem 66075-110, BrazilPrograma de Pós-Graduação em Biodiversidade e Biotecnologia da Região Norte, Universidade Federal do Tocantins, Palmas 77001-090, BrazilLaboratório de Citogenética Humana, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belem 66075-110, BrazilLaboratorio de Biologia Estrutural, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belem 66075-110, BrazilPrograma de Pós-Graduação em Farmacologia e Bioquímica, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belem 66075-110, BrazilPrograma de Pós-Graduação em Ciências Farmacêuticas, Departamento de Ciências Biológicas e da Saúde, Universidade Federal do Amapá, Macapa 68902-280, BrazilLaboratorio de Biologia Estrutural, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belem 66075-110, BrazilPrograma de Pós-Graduação em Farmacologia e Bioquímica, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belem 66075-110, BrazilGliomas 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 <i>Eleutherine plicata</i>, 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.https://www.mdpi.com/1420-3049/27/24/8850glioma C6rat brain tumor<i>Eleutherine plicata</i>eleutherinecytotoxicity |
spellingShingle | 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 In Vitro Cytotoxic Effects and Mechanisms of Action of Eleutherine Isolated from <i>Eleutherine plicata</i> Bulb in Rat Glioma C6 Cells Molecules glioma C6 rat brain tumor <i>Eleutherine plicata</i> eleutherine cytotoxicity |
title | In Vitro Cytotoxic Effects and Mechanisms of Action of Eleutherine Isolated from <i>Eleutherine plicata</i> Bulb in Rat Glioma C6 Cells |
title_full | In Vitro Cytotoxic Effects and Mechanisms of Action of Eleutherine Isolated from <i>Eleutherine plicata</i> Bulb in Rat Glioma C6 Cells |
title_fullStr | In Vitro Cytotoxic Effects and Mechanisms of Action of Eleutherine Isolated from <i>Eleutherine plicata</i> Bulb in Rat Glioma C6 Cells |
title_full_unstemmed | In Vitro Cytotoxic Effects and Mechanisms of Action of Eleutherine Isolated from <i>Eleutherine plicata</i> Bulb in Rat Glioma C6 Cells |
title_short | In Vitro Cytotoxic Effects and Mechanisms of Action of Eleutherine Isolated from <i>Eleutherine plicata</i> Bulb in Rat Glioma C6 Cells |
title_sort | in vitro cytotoxic effects and mechanisms of action of eleutherine isolated from i eleutherine plicata i bulb in rat glioma c6 cells |
topic | glioma C6 rat brain tumor <i>Eleutherine plicata</i> eleutherine cytotoxicity |
url | https://www.mdpi.com/1420-3049/27/24/8850 |
work_keys_str_mv | AT victoriamaetsuruzakishinkai invitrocytotoxiceffectsandmechanismsofactionofeleutherineisolatedfromieleutherineplicataibulbinratgliomac6cells AT izanamarizeoliveirasampaio invitrocytotoxiceffectsandmechanismsofactionofeleutherineisolatedfromieleutherineplicataibulbinratgliomac6cells AT elinegomesdossantos invitrocytotoxiceffectsandmechanismsofactionofeleutherineisolatedfromieleutherineplicataibulbinratgliomac6cells AT adanjesusgalueparra invitrocytotoxiceffectsandmechanismsofactionofeleutherineisolatedfromieleutherineplicataibulbinratgliomac6cells AT dionisiapelaesferreira invitrocytotoxiceffectsandmechanismsofactionofeleutherineisolatedfromieleutherineplicataibulbinratgliomac6cells AT driellydayannemonteirosantosbaliza invitrocytotoxiceffectsandmechanismsofactionofeleutherineisolatedfromieleutherineplicataibulbinratgliomac6cells AT neidianefariasramos invitrocytotoxiceffectsandmechanismsofactionofeleutherineisolatedfromieleutherineplicataibulbinratgliomac6cells AT raphaelsanziopimenta invitrocytotoxiceffectsandmechanismsofactionofeleutherineisolatedfromieleutherineplicataibulbinratgliomac6cells AT rommelmariorodriguezburbano invitrocytotoxiceffectsandmechanismsofactionofeleutherineisolatedfromieleutherineplicataibulbinratgliomac6cells AT chubertbernardocastrosena invitrocytotoxiceffectsandmechanismsofactionofeleutherineisolatedfromieleutherineplicataibulbinratgliomac6cells AT barbarellamatosmacchi invitrocytotoxiceffectsandmechanismsofactionofeleutherineisolatedfromieleutherineplicataibulbinratgliomac6cells AT irlonmacielferreira invitrocytotoxiceffectsandmechanismsofactionofeleutherineisolatedfromieleutherineplicataibulbinratgliomac6cells AT edileneoliveirasilva invitrocytotoxiceffectsandmechanismsofactionofeleutherineisolatedfromieleutherineplicataibulbinratgliomac6cells AT joseluizmartinsdonascimento invitrocytotoxiceffectsandmechanismsofactionofeleutherineisolatedfromieleutherineplicataibulbinratgliomac6cells |