Piperine Inhibits TGF-β Signaling Pathways and Disrupts EMT-Related Events in Human Lung Adenocarcinoma Cells
<b>Background:</b> Piperine, an amide extracted from the Piper spices, exhibits strong anti-tumor properties. However, its effect on the epithelial–mesenchymal transition (EMT) process has never been investigated. Herein, we evaluate the toxic effect of piperine on lung adenocarcinoma (A...
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MDPI AG
2020-04-01
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Online Access: | https://www.mdpi.com/2305-6320/7/4/19 |
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Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Leonardo Marques da Fonseca Lucas Rodrigues Jacques da Silva Jhenifer Santos dos Reis Marcos André Rodrigues da Costa Santos Victoria de Sousa Chaves Kelli Monteiro da Costa Julliana de Nazareth Sa-Diniz Celio Geraldo Freire de Lima Alexandre Morrot Tatiany Nunes Franklim Douglas Chaves de Alcântara-Pinto Marco Edilson Freire de Lima Jose Osvaldo Previato Lucia Mendonça-Previato Leonardo Freire-de-Lima |
spellingShingle |
Leonardo Marques da Fonseca Lucas Rodrigues Jacques da Silva Jhenifer Santos dos Reis Marcos André Rodrigues da Costa Santos Victoria de Sousa Chaves Kelli Monteiro da Costa Julliana de Nazareth Sa-Diniz Celio Geraldo Freire de Lima Alexandre Morrot Tatiany Nunes Franklim Douglas Chaves de Alcântara-Pinto Marco Edilson Freire de Lima Jose Osvaldo Previato Lucia Mendonça-Previato Leonardo Freire-de-Lima Piperine Inhibits TGF-β Signaling Pathways and Disrupts EMT-Related Events in Human Lung Adenocarcinoma Cells Medicines piperine cancer piperidinyl amide epithelial–mesenchymal transition ERK1/2 SMAD |
author_facet |
Leonardo Marques da Fonseca Lucas Rodrigues Jacques da Silva Jhenifer Santos dos Reis Marcos André Rodrigues da Costa Santos Victoria de Sousa Chaves Kelli Monteiro da Costa Julliana de Nazareth Sa-Diniz Celio Geraldo Freire de Lima Alexandre Morrot Tatiany Nunes Franklim Douglas Chaves de Alcântara-Pinto Marco Edilson Freire de Lima Jose Osvaldo Previato Lucia Mendonça-Previato Leonardo Freire-de-Lima |
author_sort |
Leonardo Marques da Fonseca |
title |
Piperine Inhibits TGF-β Signaling Pathways and Disrupts EMT-Related Events in Human Lung Adenocarcinoma Cells |
title_short |
Piperine Inhibits TGF-β Signaling Pathways and Disrupts EMT-Related Events in Human Lung Adenocarcinoma Cells |
title_full |
Piperine Inhibits TGF-β Signaling Pathways and Disrupts EMT-Related Events in Human Lung Adenocarcinoma Cells |
title_fullStr |
Piperine Inhibits TGF-β Signaling Pathways and Disrupts EMT-Related Events in Human Lung Adenocarcinoma Cells |
title_full_unstemmed |
Piperine Inhibits TGF-β Signaling Pathways and Disrupts EMT-Related Events in Human Lung Adenocarcinoma Cells |
title_sort |
piperine inhibits tgf-β signaling pathways and disrupts emt-related events in human lung adenocarcinoma cells |
publisher |
MDPI AG |
series |
Medicines |
issn |
2305-6320 |
publishDate |
2020-04-01 |
description |
<b>Background:</b> Piperine, an amide extracted from the Piper spices, exhibits strong anti-tumor properties. However, its effect on the epithelial–mesenchymal transition (EMT) process has never been investigated. Herein, we evaluate the toxic effect of piperine on lung adenocarcinoma (A549), breast adenocarcinoma (MDA-MB-231) and hepatocellular carcinoma (HepG2) cell lines, as well as its ability to inhibit EMT-related events induced by TGF-β1 treatment. <b>Methods:</b> The cell viability was investigated by MTT assay. Protein expression was evaluated by Western blot. Gene expression was monitored by real-time PCR. Zymography assay was employed to detect metalloproteinase (MMP) activity in conditioned media. Cell motility was assessed by the wound-healing and phagokinetic gold sol assays. <b>Results:</b> The results revealed that piperine was cytotoxic in concentrations over 100 µM, showing IC50 values for HepG2, MDA-MB-231 and A549 cell lines of 214, 238 and 198 µM, respectively. In order to investigate whether piperine would reverse the TGF-β1 induced-EMT, the A549 cell line was pretreated with sublethal concentrations of the natural amide followed by the addition of TGF-β1. Besides disrupting EMT-related events, piperine also inhibited both ERK 1/2 and SMAD 2 phosphorylation. <b>Conclusions:</b> These results suggest that piperine might be further used in therapeutic strategies for metastatic cancer and EMT-related disorders. |
topic |
piperine cancer piperidinyl amide epithelial–mesenchymal transition ERK1/2 SMAD |
url |
https://www.mdpi.com/2305-6320/7/4/19 |
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doaj-3aaa89762f354a4fba6d8f6a54f9fce72020-11-25T03:25:29ZengMDPI AGMedicines2305-63202020-04-017191910.3390/medicines7040019Piperine Inhibits TGF-β Signaling Pathways and Disrupts EMT-Related Events in Human Lung Adenocarcinoma CellsLeonardo Marques da Fonseca0Lucas Rodrigues Jacques da Silva1Jhenifer Santos dos Reis2Marcos André Rodrigues da Costa Santos3Victoria de Sousa Chaves4Kelli Monteiro da Costa5Julliana de Nazareth Sa-Diniz6Celio Geraldo Freire de Lima7Alexandre Morrot8Tatiany Nunes Franklim9Douglas Chaves de Alcântara-Pinto10Marco Edilson Freire de Lima11Jose Osvaldo Previato12Lucia Mendonça-Previato13Leonardo Freire-de-Lima14Laboratório de Glicobiologia, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro RJ 21941-902, BrazilLaboratório de Glicobiologia, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro RJ 21941-902, BrazilLaboratório de Glicobiologia, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro RJ 21941-902, BrazilLaboratório de Glicobiologia, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro RJ 21941-902, BrazilLaboratório de Glicobiologia, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro RJ 21941-902, BrazilLaboratório de Glicobiologia, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro RJ 21941-902, BrazilLaboratório de Glicobiologia, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro RJ 21941-902, BrazilLaboratório de Glicobiologia, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro RJ 21941-902, BrazilFaculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro RJ 21941-902, BrazilInstituto de Química, Universidade Federal Rural do Rio de Janeiro, Seropédica RJ 23851-970, BrazilInstituto de Química, Universidade Federal Rural do Rio de Janeiro, Seropédica RJ 23851-970, BrazilInstituto de Química, Universidade Federal Rural do Rio de Janeiro, Seropédica RJ 23851-970, BrazilLaboratório de Glicobiologia, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro RJ 21941-902, BrazilLaboratório de Glicobiologia, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro RJ 21941-902, BrazilLaboratório de Glicobiologia, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro RJ 21941-902, Brazil<b>Background:</b> Piperine, an amide extracted from the Piper spices, exhibits strong anti-tumor properties. However, its effect on the epithelial–mesenchymal transition (EMT) process has never been investigated. Herein, we evaluate the toxic effect of piperine on lung adenocarcinoma (A549), breast adenocarcinoma (MDA-MB-231) and hepatocellular carcinoma (HepG2) cell lines, as well as its ability to inhibit EMT-related events induced by TGF-β1 treatment. <b>Methods:</b> The cell viability was investigated by MTT assay. Protein expression was evaluated by Western blot. Gene expression was monitored by real-time PCR. Zymography assay was employed to detect metalloproteinase (MMP) activity in conditioned media. Cell motility was assessed by the wound-healing and phagokinetic gold sol assays. <b>Results:</b> The results revealed that piperine was cytotoxic in concentrations over 100 µM, showing IC50 values for HepG2, MDA-MB-231 and A549 cell lines of 214, 238 and 198 µM, respectively. In order to investigate whether piperine would reverse the TGF-β1 induced-EMT, the A549 cell line was pretreated with sublethal concentrations of the natural amide followed by the addition of TGF-β1. Besides disrupting EMT-related events, piperine also inhibited both ERK 1/2 and SMAD 2 phosphorylation. <b>Conclusions:</b> These results suggest that piperine might be further used in therapeutic strategies for metastatic cancer and EMT-related disorders.https://www.mdpi.com/2305-6320/7/4/19piperinecancerpiperidinyl amideepithelial–mesenchymal transitionERK1/2SMAD |