Ethanolic Extract of Senna velutina Roots: Chemical Composition, In Vitro and In Vivo Antitumor Effects, and B16F10-Nex2 Melanoma Cell Death Mechanisms
Cutaneous melanoma is among the most aggressive types of cancer, and its rate of occurrence increases every year. Current pharmacological treatments for melanoma are not completely effective, requiring the identification of new drugs. As an alternative, plant-derived natural compounds are described...
Main Authors: | , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Hindawi Limited
2019-01-01
|
Series: | Oxidative Medicine and Cellular Longevity |
Online Access: | http://dx.doi.org/10.1155/2019/5719483 |
id |
doaj-298645ee05da4bf3acbb37186989c28d |
---|---|
record_format |
Article |
spelling |
doaj-298645ee05da4bf3acbb37186989c28d2020-11-24T23:55:37ZengHindawi LimitedOxidative Medicine and Cellular Longevity1942-09001942-09942019-01-01201910.1155/2019/57194835719483Ethanolic Extract of Senna velutina Roots: Chemical Composition, In Vitro and In Vivo Antitumor Effects, and B16F10-Nex2 Melanoma Cell Death MechanismsDavid Tsuyoshi Hiramatsu Castro0Jaqueline Ferreira Campos1Marcio José Damião2Heron Fernandes Vieira Torquato3Edgar Julian Paredes-Gamero4Carlos Alexandre Carollo5Elaine Guadelupe Rodrigues6Kely de Picoli Souza7Edson Lucas dos Santos8Research Group on Biotechnology and Bioprospecting Applied to Metabolism (GEBBAM), Federal University of Grande Dourados, Dourados, CEP: 79804-970 MS, BrazilResearch Group on Biotechnology and Bioprospecting Applied to Metabolism (GEBBAM), Federal University of Grande Dourados, Dourados, CEP: 79804-970 MS, BrazilResearch Group on Biotechnology and Bioprospecting Applied to Metabolism (GEBBAM), Federal University of Grande Dourados, Dourados, CEP: 79804-970 MS, BrazilDepartment of Biochemistry, Federal University of São Paulo, São Paulo, CEP: 04044-020, SP, BrazilDepartment of Biochemistry, Federal University of São Paulo, São Paulo, CEP: 04044-020, SP, BrazilLaboratory of Natural Products and Mass Spectrometry, Federal University of Mato Grosso do Sul, Campo Grande, CEP: 79070-900 MS, BrazilDepartment of Microbiology, Immunology, and Parasitology, Paulista School of Medicine, Federal University of São Paulo (EPM-UNIFESP), São Paulo, CEP: 04023-062 SP, BrazilResearch Group on Biotechnology and Bioprospecting Applied to Metabolism (GEBBAM), Federal University of Grande Dourados, Dourados, CEP: 79804-970 MS, BrazilResearch Group on Biotechnology and Bioprospecting Applied to Metabolism (GEBBAM), Federal University of Grande Dourados, Dourados, CEP: 79804-970 MS, BrazilCutaneous melanoma is among the most aggressive types of cancer, and its rate of occurrence increases every year. Current pharmacological treatments for melanoma are not completely effective, requiring the identification of new drugs. As an alternative, plant-derived natural compounds are described as promising sources of new anticancer drugs. In this context, the objectives of this study were to identify the chemical composition of the ethanolic extract of Senna velutina roots (ESVR), to assess its in vitro and in vivo antitumor effects on melanoma cells, and to characterize its mechanisms of action. For these purposes, the chemical constituents were identified by liquid chromatography coupled to high-resolution mass spectrometry. The in vitro activity of the extract was assessed in the B16F10-Nex2 melanoma cell line using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and based on the apoptotic cell count; DNA fragmentation; necrostatin-1 inhibition; intracellular calcium, pan-caspase, and caspase-3 activation; reactive oxygen species (ROS) levels; and cell cycle arrest. The in vivo activity of the extract was assessed in models of tumor volume progression and pulmonary nodule formation in C57Bl/6 mice. The chemical composition results showed that ESVR contains flavonoid derivatives of the catechin, anthraquinone, and piceatannol groups. The extract reduced B16F10-Nex2 cell viability and promoted apoptotic cell death as well as caspase-3 activation, with increased intracellular calcium and ROS levels as well as cell cycle arrest at the sub-G0/G1 phase. In vivo, the tumor volume progression and pulmonary metastasis of ESVR-treated mice decreased over 50%. Combined, these results show that ESVR had in vitro and in vivo antitumor effects, predominantly by apoptosis, thus demonstrating its potential as a therapeutic agent in the treatment of melanoma and other types of cancer.http://dx.doi.org/10.1155/2019/5719483 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
David Tsuyoshi Hiramatsu Castro Jaqueline Ferreira Campos Marcio José Damião Heron Fernandes Vieira Torquato Edgar Julian Paredes-Gamero Carlos Alexandre Carollo Elaine Guadelupe Rodrigues Kely de Picoli Souza Edson Lucas dos Santos |
spellingShingle |
David Tsuyoshi Hiramatsu Castro Jaqueline Ferreira Campos Marcio José Damião Heron Fernandes Vieira Torquato Edgar Julian Paredes-Gamero Carlos Alexandre Carollo Elaine Guadelupe Rodrigues Kely de Picoli Souza Edson Lucas dos Santos Ethanolic Extract of Senna velutina Roots: Chemical Composition, In Vitro and In Vivo Antitumor Effects, and B16F10-Nex2 Melanoma Cell Death Mechanisms Oxidative Medicine and Cellular Longevity |
author_facet |
David Tsuyoshi Hiramatsu Castro Jaqueline Ferreira Campos Marcio José Damião Heron Fernandes Vieira Torquato Edgar Julian Paredes-Gamero Carlos Alexandre Carollo Elaine Guadelupe Rodrigues Kely de Picoli Souza Edson Lucas dos Santos |
author_sort |
David Tsuyoshi Hiramatsu Castro |
title |
Ethanolic Extract of Senna velutina Roots: Chemical Composition, In Vitro and In Vivo Antitumor Effects, and B16F10-Nex2 Melanoma Cell Death Mechanisms |
title_short |
Ethanolic Extract of Senna velutina Roots: Chemical Composition, In Vitro and In Vivo Antitumor Effects, and B16F10-Nex2 Melanoma Cell Death Mechanisms |
title_full |
Ethanolic Extract of Senna velutina Roots: Chemical Composition, In Vitro and In Vivo Antitumor Effects, and B16F10-Nex2 Melanoma Cell Death Mechanisms |
title_fullStr |
Ethanolic Extract of Senna velutina Roots: Chemical Composition, In Vitro and In Vivo Antitumor Effects, and B16F10-Nex2 Melanoma Cell Death Mechanisms |
title_full_unstemmed |
Ethanolic Extract of Senna velutina Roots: Chemical Composition, In Vitro and In Vivo Antitumor Effects, and B16F10-Nex2 Melanoma Cell Death Mechanisms |
title_sort |
ethanolic extract of senna velutina roots: chemical composition, in vitro and in vivo antitumor effects, and b16f10-nex2 melanoma cell death mechanisms |
publisher |
Hindawi Limited |
series |
Oxidative Medicine and Cellular Longevity |
issn |
1942-0900 1942-0994 |
publishDate |
2019-01-01 |
description |
Cutaneous melanoma is among the most aggressive types of cancer, and its rate of occurrence increases every year. Current pharmacological treatments for melanoma are not completely effective, requiring the identification of new drugs. As an alternative, plant-derived natural compounds are described as promising sources of new anticancer drugs. In this context, the objectives of this study were to identify the chemical composition of the ethanolic extract of Senna velutina roots (ESVR), to assess its in vitro and in vivo antitumor effects on melanoma cells, and to characterize its mechanisms of action. For these purposes, the chemical constituents were identified by liquid chromatography coupled to high-resolution mass spectrometry. The in vitro activity of the extract was assessed in the B16F10-Nex2 melanoma cell line using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and based on the apoptotic cell count; DNA fragmentation; necrostatin-1 inhibition; intracellular calcium, pan-caspase, and caspase-3 activation; reactive oxygen species (ROS) levels; and cell cycle arrest. The in vivo activity of the extract was assessed in models of tumor volume progression and pulmonary nodule formation in C57Bl/6 mice. The chemical composition results showed that ESVR contains flavonoid derivatives of the catechin, anthraquinone, and piceatannol groups. The extract reduced B16F10-Nex2 cell viability and promoted apoptotic cell death as well as caspase-3 activation, with increased intracellular calcium and ROS levels as well as cell cycle arrest at the sub-G0/G1 phase. In vivo, the tumor volume progression and pulmonary metastasis of ESVR-treated mice decreased over 50%. Combined, these results show that ESVR had in vitro and in vivo antitumor effects, predominantly by apoptosis, thus demonstrating its potential as a therapeutic agent in the treatment of melanoma and other types of cancer. |
url |
http://dx.doi.org/10.1155/2019/5719483 |
work_keys_str_mv |
AT davidtsuyoshihiramatsucastro ethanolicextractofsennavelutinarootschemicalcompositioninvitroandinvivoantitumoreffectsandb16f10nex2melanomacelldeathmechanisms AT jaquelineferreiracampos ethanolicextractofsennavelutinarootschemicalcompositioninvitroandinvivoantitumoreffectsandb16f10nex2melanomacelldeathmechanisms AT marciojosedamiao ethanolicextractofsennavelutinarootschemicalcompositioninvitroandinvivoantitumoreffectsandb16f10nex2melanomacelldeathmechanisms AT heronfernandesvieiratorquato ethanolicextractofsennavelutinarootschemicalcompositioninvitroandinvivoantitumoreffectsandb16f10nex2melanomacelldeathmechanisms AT edgarjulianparedesgamero ethanolicextractofsennavelutinarootschemicalcompositioninvitroandinvivoantitumoreffectsandb16f10nex2melanomacelldeathmechanisms AT carlosalexandrecarollo ethanolicextractofsennavelutinarootschemicalcompositioninvitroandinvivoantitumoreffectsandb16f10nex2melanomacelldeathmechanisms AT elaineguadeluperodrigues ethanolicextractofsennavelutinarootschemicalcompositioninvitroandinvivoantitumoreffectsandb16f10nex2melanomacelldeathmechanisms AT kelydepicolisouza ethanolicextractofsennavelutinarootschemicalcompositioninvitroandinvivoantitumoreffectsandb16f10nex2melanomacelldeathmechanisms AT edsonlucasdossantos ethanolicextractofsennavelutinarootschemicalcompositioninvitroandinvivoantitumoreffectsandb16f10nex2melanomacelldeathmechanisms |
_version_ |
1725461484911198208 |