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Treatment of 13-cis retinoic acid and 1,25-dihydroxyvitamin D3 inhibits TNF-alpha-mediated expression of MMP-9 protein and cell invasion through the suppression of JNK pathway and microRNA 221 in human pancreatic adenocarcinoma cancer cells

Human pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer type with a very high mortality rate. Inflammatory cytokine such as tumor necrosis factor- alpha (TNF-α) plays a pivotal role in the progression of PDAC. Recently, suppression of cell invasion by preventive agents has received consider...

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Autores principales: Cheng, Yen-Huang, Chiang, En-Pei Isabel, Syu, Jia-Ning, Chao, Che-Yi, Lin, Hung-Yu, Lin, Cheng-Chieh, Yang, Mei-Due, Tsai, Shu-Yao, Tang, Feng-Yao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968633/
https://www.ncbi.nlm.nih.gov/pubmed/33730072
http://dx.doi.org/10.1371/journal.pone.0247550
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author Cheng, Yen-Huang
Chiang, En-Pei Isabel
Syu, Jia-Ning
Chao, Che-Yi
Lin, Hung-Yu
Lin, Cheng-Chieh
Yang, Mei-Due
Tsai, Shu-Yao
Tang, Feng-Yao
author_facet Cheng, Yen-Huang
Chiang, En-Pei Isabel
Syu, Jia-Ning
Chao, Che-Yi
Lin, Hung-Yu
Lin, Cheng-Chieh
Yang, Mei-Due
Tsai, Shu-Yao
Tang, Feng-Yao
author_sort Cheng, Yen-Huang
collection PubMed
description Human pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer type with a very high mortality rate. Inflammatory cytokine such as tumor necrosis factor- alpha (TNF-α) plays a pivotal role in the progression of PDAC. Recently, suppression of cell invasion by preventive agents has received considerable attention in the prevention of metastatic tumors. Several clinical studies suggested that natural forms or analogues of fat-soluble vitamins such as vitamin A and vitamin D can work as anti-cancer agents to inhibit the development of cancer. In this study, our results demonstrated that co-treatment of 13-cis retinoic acid (13-cis RA) and 1,25-dihydroxyvitamin D3 (1,25-VD3) significantly inhibited TNF-α mediated cell invasion in PDAC in vitro. Cotreatment of 13-cis RA and 1,25-VD3 also inhibited TNF-α mediated expression of matrix metalloproteinase-9 (MMP-9) protein through blocking c-Jun N-terminal kinase (JNK) and nuclear factor kappa B (NF-κB) signaling pathways. Our results demonstrated that treatment of TNF-α lead to a decreased expression of tissue inhibitor of metalloproteinase- 3 (TIMP-3) protein and an induction of MMP-9 protein and cell invasion through an upregulation of microRNA-221 (miR-221) in human PDAC cells. Moreover, treatment of SP600125 (a specific inhibitor of JNK pathway) or cotreatment of 13-cis RA and 1,25-VD3 significantly induced a decreased expression of miR-221 and an increased expression of TIMP-3 protein. These results suggest that 13-cis RA and 1,25-VD3 significantly suppress TNF-α mediated cell invasion and therefore potentially act as preventive agents against PDAC.
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spelling pubmed-79686332021-03-31 Treatment of 13-cis retinoic acid and 1,25-dihydroxyvitamin D3 inhibits TNF-alpha-mediated expression of MMP-9 protein and cell invasion through the suppression of JNK pathway and microRNA 221 in human pancreatic adenocarcinoma cancer cells Cheng, Yen-Huang Chiang, En-Pei Isabel Syu, Jia-Ning Chao, Che-Yi Lin, Hung-Yu Lin, Cheng-Chieh Yang, Mei-Due Tsai, Shu-Yao Tang, Feng-Yao PLoS One Research Article Human pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer type with a very high mortality rate. Inflammatory cytokine such as tumor necrosis factor- alpha (TNF-α) plays a pivotal role in the progression of PDAC. Recently, suppression of cell invasion by preventive agents has received considerable attention in the prevention of metastatic tumors. Several clinical studies suggested that natural forms or analogues of fat-soluble vitamins such as vitamin A and vitamin D can work as anti-cancer agents to inhibit the development of cancer. In this study, our results demonstrated that co-treatment of 13-cis retinoic acid (13-cis RA) and 1,25-dihydroxyvitamin D3 (1,25-VD3) significantly inhibited TNF-α mediated cell invasion in PDAC in vitro. Cotreatment of 13-cis RA and 1,25-VD3 also inhibited TNF-α mediated expression of matrix metalloproteinase-9 (MMP-9) protein through blocking c-Jun N-terminal kinase (JNK) and nuclear factor kappa B (NF-κB) signaling pathways. Our results demonstrated that treatment of TNF-α lead to a decreased expression of tissue inhibitor of metalloproteinase- 3 (TIMP-3) protein and an induction of MMP-9 protein and cell invasion through an upregulation of microRNA-221 (miR-221) in human PDAC cells. Moreover, treatment of SP600125 (a specific inhibitor of JNK pathway) or cotreatment of 13-cis RA and 1,25-VD3 significantly induced a decreased expression of miR-221 and an increased expression of TIMP-3 protein. These results suggest that 13-cis RA and 1,25-VD3 significantly suppress TNF-α mediated cell invasion and therefore potentially act as preventive agents against PDAC. Public Library of Science 2021-03-17 /pmc/articles/PMC7968633/ /pubmed/33730072 http://dx.doi.org/10.1371/journal.pone.0247550 Text en © 2021 Cheng et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Cheng, Yen-Huang
Chiang, En-Pei Isabel
Syu, Jia-Ning
Chao, Che-Yi
Lin, Hung-Yu
Lin, Cheng-Chieh
Yang, Mei-Due
Tsai, Shu-Yao
Tang, Feng-Yao
Treatment of 13-cis retinoic acid and 1,25-dihydroxyvitamin D3 inhibits TNF-alpha-mediated expression of MMP-9 protein and cell invasion through the suppression of JNK pathway and microRNA 221 in human pancreatic adenocarcinoma cancer cells
title Treatment of 13-cis retinoic acid and 1,25-dihydroxyvitamin D3 inhibits TNF-alpha-mediated expression of MMP-9 protein and cell invasion through the suppression of JNK pathway and microRNA 221 in human pancreatic adenocarcinoma cancer cells
title_full Treatment of 13-cis retinoic acid and 1,25-dihydroxyvitamin D3 inhibits TNF-alpha-mediated expression of MMP-9 protein and cell invasion through the suppression of JNK pathway and microRNA 221 in human pancreatic adenocarcinoma cancer cells
title_fullStr Treatment of 13-cis retinoic acid and 1,25-dihydroxyvitamin D3 inhibits TNF-alpha-mediated expression of MMP-9 protein and cell invasion through the suppression of JNK pathway and microRNA 221 in human pancreatic adenocarcinoma cancer cells
title_full_unstemmed Treatment of 13-cis retinoic acid and 1,25-dihydroxyvitamin D3 inhibits TNF-alpha-mediated expression of MMP-9 protein and cell invasion through the suppression of JNK pathway and microRNA 221 in human pancreatic adenocarcinoma cancer cells
title_short Treatment of 13-cis retinoic acid and 1,25-dihydroxyvitamin D3 inhibits TNF-alpha-mediated expression of MMP-9 protein and cell invasion through the suppression of JNK pathway and microRNA 221 in human pancreatic adenocarcinoma cancer cells
title_sort treatment of 13-cis retinoic acid and 1,25-dihydroxyvitamin d3 inhibits tnf-alpha-mediated expression of mmp-9 protein and cell invasion through the suppression of jnk pathway and microrna 221 in human pancreatic adenocarcinoma cancer cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968633/
https://www.ncbi.nlm.nih.gov/pubmed/33730072
http://dx.doi.org/10.1371/journal.pone.0247550
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