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Epithelial-to-Mesenchymal Transition Is Not a Major Modulating Factor in the Cytotoxic Response to Natural Products in Cancer Cell Lines

Numerous natural products exhibit antiproliferative activity against cancer cells by modulating various biological pathways. In this study, we investigated the potential use of eight natural compounds (apigenin, curcumin, epigallocatechin gallate, fisetin, forskolin, procyanidin B2, resveratrol, uro...

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Autores principales: Kucukkaraduman, Baris, Cicek, Ekin Gokce, Akbar, Muhammad Waqas, Demirkol Canli, Secil, Vural, Burcak, Gure, Ali Osmay
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8512490/
https://www.ncbi.nlm.nih.gov/pubmed/34641401
http://dx.doi.org/10.3390/molecules26195858
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author Kucukkaraduman, Baris
Cicek, Ekin Gokce
Akbar, Muhammad Waqas
Demirkol Canli, Secil
Vural, Burcak
Gure, Ali Osmay
author_facet Kucukkaraduman, Baris
Cicek, Ekin Gokce
Akbar, Muhammad Waqas
Demirkol Canli, Secil
Vural, Burcak
Gure, Ali Osmay
author_sort Kucukkaraduman, Baris
collection PubMed
description Numerous natural products exhibit antiproliferative activity against cancer cells by modulating various biological pathways. In this study, we investigated the potential use of eight natural compounds (apigenin, curcumin, epigallocatechin gallate, fisetin, forskolin, procyanidin B2, resveratrol, urolithin A) and two repurposed agents (fulvestrant and metformin) as chemotherapy enhancers and mesenchymal-to-epithelial (MET) inducers of cancer cells. Screening of these compounds in various colon, breast, and pancreatic cancer cell lines revealed anti-cancer activity for all compounds, with curcumin being the most effective among these in all cell lines. Although some of the natural products were able to induce MET in some cancer cell lines, the MET induction was not related to increased synergy with either 5-FU, irinotecan, gemcitabine, or gefitinib. When synergy was observed, for example with curcumin and irinotecan, this was unrelated to MET induction, as assessed by changes in E-cadherin and vimentin expression. Our results show that MET induction is compound and cell line specific, and that MET is not necessarily related to enhanced chemosensitivity.
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spelling pubmed-85124902021-10-14 Epithelial-to-Mesenchymal Transition Is Not a Major Modulating Factor in the Cytotoxic Response to Natural Products in Cancer Cell Lines Kucukkaraduman, Baris Cicek, Ekin Gokce Akbar, Muhammad Waqas Demirkol Canli, Secil Vural, Burcak Gure, Ali Osmay Molecules Article Numerous natural products exhibit antiproliferative activity against cancer cells by modulating various biological pathways. In this study, we investigated the potential use of eight natural compounds (apigenin, curcumin, epigallocatechin gallate, fisetin, forskolin, procyanidin B2, resveratrol, urolithin A) and two repurposed agents (fulvestrant and metformin) as chemotherapy enhancers and mesenchymal-to-epithelial (MET) inducers of cancer cells. Screening of these compounds in various colon, breast, and pancreatic cancer cell lines revealed anti-cancer activity for all compounds, with curcumin being the most effective among these in all cell lines. Although some of the natural products were able to induce MET in some cancer cell lines, the MET induction was not related to increased synergy with either 5-FU, irinotecan, gemcitabine, or gefitinib. When synergy was observed, for example with curcumin and irinotecan, this was unrelated to MET induction, as assessed by changes in E-cadherin and vimentin expression. Our results show that MET induction is compound and cell line specific, and that MET is not necessarily related to enhanced chemosensitivity. MDPI 2021-09-27 /pmc/articles/PMC8512490/ /pubmed/34641401 http://dx.doi.org/10.3390/molecules26195858 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kucukkaraduman, Baris
Cicek, Ekin Gokce
Akbar, Muhammad Waqas
Demirkol Canli, Secil
Vural, Burcak
Gure, Ali Osmay
Epithelial-to-Mesenchymal Transition Is Not a Major Modulating Factor in the Cytotoxic Response to Natural Products in Cancer Cell Lines
title Epithelial-to-Mesenchymal Transition Is Not a Major Modulating Factor in the Cytotoxic Response to Natural Products in Cancer Cell Lines
title_full Epithelial-to-Mesenchymal Transition Is Not a Major Modulating Factor in the Cytotoxic Response to Natural Products in Cancer Cell Lines
title_fullStr Epithelial-to-Mesenchymal Transition Is Not a Major Modulating Factor in the Cytotoxic Response to Natural Products in Cancer Cell Lines
title_full_unstemmed Epithelial-to-Mesenchymal Transition Is Not a Major Modulating Factor in the Cytotoxic Response to Natural Products in Cancer Cell Lines
title_short Epithelial-to-Mesenchymal Transition Is Not a Major Modulating Factor in the Cytotoxic Response to Natural Products in Cancer Cell Lines
title_sort epithelial-to-mesenchymal transition is not a major modulating factor in the cytotoxic response to natural products in cancer cell lines
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8512490/
https://www.ncbi.nlm.nih.gov/pubmed/34641401
http://dx.doi.org/10.3390/molecules26195858
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