The effect of acyclic retinoid on the metabolomic profiles of hepatocytes and hepatocellular carcinoma cells.
<h4>Background/purpose</h4>Acyclic retinoid (ACR) is a promising chemopreventive agent for hepatocellular carcinoma (HCC) that selectively inhibits the growth of HCC cells (JHH7) but not normal hepatic cells (Hc). To better understand the molecular basis of the selective anti-cancer effe...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2013-01-01
|
Series: | PLoS ONE |
Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24376596/pdf/?tool=EBI |
id |
doaj-1397b248f88a48d3ae73eb636ce2a47b |
---|---|
record_format |
Article |
spelling |
doaj-1397b248f88a48d3ae73eb636ce2a47b2021-03-04T10:05:06ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01812e8286010.1371/journal.pone.0082860The effect of acyclic retinoid on the metabolomic profiles of hepatocytes and hepatocellular carcinoma cells.Xian-Yang QinFeifei WeiMasaru TanokuraNaoto IshibashiMasahito ShimizuHisataka MoriwakiSoichi Kojima<h4>Background/purpose</h4>Acyclic retinoid (ACR) is a promising chemopreventive agent for hepatocellular carcinoma (HCC) that selectively inhibits the growth of HCC cells (JHH7) but not normal hepatic cells (Hc). To better understand the molecular basis of the selective anti-cancer effect of ACR, we performed nuclear magnetic resonance (NMR)-based and capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS)-based metabolome analyses in JHH7 and Hc cells after treatment with ACR.<h4>Methodology/principal findings</h4>NMR-based metabolomics revealed a distinct metabolomic profile of JHH7 cells at 18 h after ACR treatment but not at 4 h after ACR treatment. CE-TOFMS analysis identified 88 principal metabolites in JHH7 and Hc cells after 24 h of treatment with ethanol (EtOH) or ACR. The abundance of 71 of these metabolites was significantly different between EtOH-treated control JHH7 and Hc cells, and 49 of these metabolites were significantly down-regulated in the ACR-treated JHH7 cells compared to the EtOH-treated JHH7 cells. Of particular interest, the increase in adenosine-5'-triphosphate (ATP), the main cellular energy source, that was observed in the EtOH-treated control JHH7 cells was almost completely suppressed in the ACR-treated JHH7 cells; treatment with ACR restored ATP to the basal levels observed in both EtOH-control and ACR-treated Hc cells (0.72-fold compared to the EtOH control-treated JHH7 cells). Moreover, real-time PCR analyses revealed that ACR significantly increased the expression of pyruvate dehydrogenase kinases 4 (PDK4), a key regulator of ATP production, in JHH7 cells but not in Hc cells (3.06-fold and 1.20-fold compared to the EtOH control, respectively).<h4>Conclusions/significance</h4>The results of the present study suggest that ACR may suppress the enhanced energy metabolism of JHH7 cells but not Hc cells; this occurs at least in part via the cancer-selective enhancement of PDK4 expression. The cancer-selective metabolic pathways identified in this study will be important targets of the anti-cancer activity of ACR.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24376596/pdf/?tool=EBI |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xian-Yang Qin Feifei Wei Masaru Tanokura Naoto Ishibashi Masahito Shimizu Hisataka Moriwaki Soichi Kojima |
spellingShingle |
Xian-Yang Qin Feifei Wei Masaru Tanokura Naoto Ishibashi Masahito Shimizu Hisataka Moriwaki Soichi Kojima The effect of acyclic retinoid on the metabolomic profiles of hepatocytes and hepatocellular carcinoma cells. PLoS ONE |
author_facet |
Xian-Yang Qin Feifei Wei Masaru Tanokura Naoto Ishibashi Masahito Shimizu Hisataka Moriwaki Soichi Kojima |
author_sort |
Xian-Yang Qin |
title |
The effect of acyclic retinoid on the metabolomic profiles of hepatocytes and hepatocellular carcinoma cells. |
title_short |
The effect of acyclic retinoid on the metabolomic profiles of hepatocytes and hepatocellular carcinoma cells. |
title_full |
The effect of acyclic retinoid on the metabolomic profiles of hepatocytes and hepatocellular carcinoma cells. |
title_fullStr |
The effect of acyclic retinoid on the metabolomic profiles of hepatocytes and hepatocellular carcinoma cells. |
title_full_unstemmed |
The effect of acyclic retinoid on the metabolomic profiles of hepatocytes and hepatocellular carcinoma cells. |
title_sort |
effect of acyclic retinoid on the metabolomic profiles of hepatocytes and hepatocellular carcinoma cells. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2013-01-01 |
description |
<h4>Background/purpose</h4>Acyclic retinoid (ACR) is a promising chemopreventive agent for hepatocellular carcinoma (HCC) that selectively inhibits the growth of HCC cells (JHH7) but not normal hepatic cells (Hc). To better understand the molecular basis of the selective anti-cancer effect of ACR, we performed nuclear magnetic resonance (NMR)-based and capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS)-based metabolome analyses in JHH7 and Hc cells after treatment with ACR.<h4>Methodology/principal findings</h4>NMR-based metabolomics revealed a distinct metabolomic profile of JHH7 cells at 18 h after ACR treatment but not at 4 h after ACR treatment. CE-TOFMS analysis identified 88 principal metabolites in JHH7 and Hc cells after 24 h of treatment with ethanol (EtOH) or ACR. The abundance of 71 of these metabolites was significantly different between EtOH-treated control JHH7 and Hc cells, and 49 of these metabolites were significantly down-regulated in the ACR-treated JHH7 cells compared to the EtOH-treated JHH7 cells. Of particular interest, the increase in adenosine-5'-triphosphate (ATP), the main cellular energy source, that was observed in the EtOH-treated control JHH7 cells was almost completely suppressed in the ACR-treated JHH7 cells; treatment with ACR restored ATP to the basal levels observed in both EtOH-control and ACR-treated Hc cells (0.72-fold compared to the EtOH control-treated JHH7 cells). Moreover, real-time PCR analyses revealed that ACR significantly increased the expression of pyruvate dehydrogenase kinases 4 (PDK4), a key regulator of ATP production, in JHH7 cells but not in Hc cells (3.06-fold and 1.20-fold compared to the EtOH control, respectively).<h4>Conclusions/significance</h4>The results of the present study suggest that ACR may suppress the enhanced energy metabolism of JHH7 cells but not Hc cells; this occurs at least in part via the cancer-selective enhancement of PDK4 expression. The cancer-selective metabolic pathways identified in this study will be important targets of the anti-cancer activity of ACR. |
url |
https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24376596/pdf/?tool=EBI |
work_keys_str_mv |
AT xianyangqin theeffectofacyclicretinoidonthemetabolomicprofilesofhepatocytesandhepatocellularcarcinomacells AT feifeiwei theeffectofacyclicretinoidonthemetabolomicprofilesofhepatocytesandhepatocellularcarcinomacells AT masarutanokura theeffectofacyclicretinoidonthemetabolomicprofilesofhepatocytesandhepatocellularcarcinomacells AT naotoishibashi theeffectofacyclicretinoidonthemetabolomicprofilesofhepatocytesandhepatocellularcarcinomacells AT masahitoshimizu theeffectofacyclicretinoidonthemetabolomicprofilesofhepatocytesandhepatocellularcarcinomacells AT hisatakamoriwaki theeffectofacyclicretinoidonthemetabolomicprofilesofhepatocytesandhepatocellularcarcinomacells AT soichikojima theeffectofacyclicretinoidonthemetabolomicprofilesofhepatocytesandhepatocellularcarcinomacells AT xianyangqin effectofacyclicretinoidonthemetabolomicprofilesofhepatocytesandhepatocellularcarcinomacells AT feifeiwei effectofacyclicretinoidonthemetabolomicprofilesofhepatocytesandhepatocellularcarcinomacells AT masarutanokura effectofacyclicretinoidonthemetabolomicprofilesofhepatocytesandhepatocellularcarcinomacells AT naotoishibashi effectofacyclicretinoidonthemetabolomicprofilesofhepatocytesandhepatocellularcarcinomacells AT masahitoshimizu effectofacyclicretinoidonthemetabolomicprofilesofhepatocytesandhepatocellularcarcinomacells AT hisatakamoriwaki effectofacyclicretinoidonthemetabolomicprofilesofhepatocytesandhepatocellularcarcinomacells AT soichikojima effectofacyclicretinoidonthemetabolomicprofilesofhepatocytesandhepatocellularcarcinomacells |
_version_ |
1714806658083848192 |