Metformin promotes apoptosis in hepatocellular carcinoma through the CEBPD-induced autophagy pathway.
Identifieur interne : 000800 ( Main/Exploration ); précédent : 000799; suivant : 000801Metformin promotes apoptosis in hepatocellular carcinoma through the CEBPD-induced autophagy pathway.
Auteurs : Hsin-Hwa Tsai [Taïwan] ; Hong-Yue Lai [Taïwan] ; Yueh-Chiu Chen [Taïwan] ; Chien-Feng Li [Taïwan] ; Huei-Sheng Huang [Taïwan] ; Hsiao-Sheng Liu [Taïwan] ; Yau-Sheng Tsai [Taïwan] ; Ju-Ming Wang [Taïwan]Source :
- Oncotarget [ 1949-2553 ] ; 2017.
Descripteurs français
- KwdFr :
- Animaux (MeSH), Antinéoplasiques (pharmacologie), Apoptose (effets des médicaments et des substances chimiques), Autophagie (effets des médicaments et des substances chimiques), Carcinome hépatocellulaire (métabolisme), Cytométrie en flux (MeSH), Humains (MeSH), Hypoglycémiants (pharmacologie), Hétérogreffes (MeSH), Immunoprécipitation de la chromatine (MeSH), Lignée cellulaire tumorale (MeSH), Metformine (pharmacologie), Microscopie de fluorescence (MeSH), Mâle (MeSH), Protéine delta liant les séquences stimulatrices de type CCAAT (métabolisme), Réaction de polymérisation en chaîne (MeSH), Souris (MeSH), Souris SCID (MeSH), Souris de lignée NOD (MeSH), Technique de Western (MeSH), Techniques de knock-down de gènes (MeSH), Tumeurs du foie (métabolisme).
- MESH :
- effets des médicaments et des substances chimiques : Apoptose, Autophagie.
- métabolisme : Carcinome hépatocellulaire, Protéine delta liant les séquences stimulatrices de type CCAAT, Tumeurs du foie.
- pharmacologie : Antinéoplasiques, Hypoglycémiants, Metformine.
- Animaux, Cytométrie en flux, Humains, Hétérogreffes, Immunoprécipitation de la chromatine, Lignée cellulaire tumorale, Microscopie de fluorescence, Mâle, Réaction de polymérisation en chaîne, Souris, Souris SCID, Souris de lignée NOD, Technique de Western, Techniques de knock-down de gènes.
English descriptors
- KwdEn :
- Animals (MeSH), Antineoplastic Agents (pharmacology), Apoptosis (drug effects), Autophagy (drug effects), Blotting, Western (MeSH), CCAAT-Enhancer-Binding Protein-delta (metabolism), Carcinoma, Hepatocellular (metabolism), Cell Line, Tumor (MeSH), Chromatin Immunoprecipitation (MeSH), Flow Cytometry (MeSH), Gene Knockdown Techniques (MeSH), Heterografts (MeSH), Humans (MeSH), Hypoglycemic Agents (pharmacology), Liver Neoplasms (metabolism), Male (MeSH), Metformin (pharmacology), Mice (MeSH), Mice, Inbred NOD (MeSH), Mice, SCID (MeSH), Microscopy, Fluorescence (MeSH), Polymerase Chain Reaction (MeSH).
- MESH :
- chemical , metabolism : CCAAT-Enhancer-Binding Protein-delta.
- chemical , pharmacology : Antineoplastic Agents, Hypoglycemic Agents, Metformin.
- drug effects : Apoptosis, Autophagy.
- metabolism : Carcinoma, Hepatocellular, Liver Neoplasms.
- Animals, Blotting, Western, Cell Line, Tumor, Chromatin Immunoprecipitation, Flow Cytometry, Gene Knockdown Techniques, Heterografts, Humans, Male, Mice, Mice, Inbred NOD, Mice, SCID, Microscopy, Fluorescence, Polymerase Chain Reaction.
Abstract
Metformin, as an AMP-activated protein kinase (AMPK) activator, can activate autophagy. A study showed that metformin decreased the risk of hepatocellular carcinoma (HCC) in diabetic patients. However, the detailed mechanism in the metformin-mediated anticancer effect remains an open question. Transcription factor CCAAT/enhancer-binding protein delta (CEBPD) has been suggested to serve as a tumor suppressor and is responsive to multiple anticancer drugs in HCC. In this study, we found that CEBPD and autophagy are involved in metformin-induced cell apoptosis in Huh7 cells. The underlying mechanisms in this process included a reduction in Src-mediated CEBPD protein degradation and an increase in CEBPD-regulated LC3B and ATG3 gene transcription under metformin treatment. We also found that AMPK is involved in metformin-induced CEBPD expression. Combined treatment with metformin and rapamycin can enhance autophagic cell death through the AMPK-dependent and AMPK-independent pathway, respectively. Taken together, we provide a new insight and therapeutic approach by targeting autophagy in the treatment of HCC.
DOI: 10.18632/oncotarget.14640
PubMed: 28099155
PubMed Central: PMC5355142
Affiliations:
Links toward previous steps (curation, corpus...)
Le document en format XML
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals (MeSH)</term>
<term>Antineoplastic Agents (pharmacology)</term>
<term>Apoptosis (drug effects)</term>
<term>Autophagy (drug effects)</term>
<term>Blotting, Western (MeSH)</term>
<term>CCAAT-Enhancer-Binding Protein-delta (metabolism)</term>
<term>Carcinoma, Hepatocellular (metabolism)</term>
<term>Cell Line, Tumor (MeSH)</term>
<term>Chromatin Immunoprecipitation (MeSH)</term>
<term>Flow Cytometry (MeSH)</term>
<term>Gene Knockdown Techniques (MeSH)</term>
<term>Heterografts (MeSH)</term>
<term>Humans (MeSH)</term>
<term>Hypoglycemic Agents (pharmacology)</term>
<term>Liver Neoplasms (metabolism)</term>
<term>Male (MeSH)</term>
<term>Metformin (pharmacology)</term>
<term>Mice (MeSH)</term>
<term>Mice, Inbred NOD (MeSH)</term>
<term>Mice, SCID (MeSH)</term>
<term>Microscopy, Fluorescence (MeSH)</term>
<term>Polymerase Chain Reaction (MeSH)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Animaux (MeSH)</term>
<term>Antinéoplasiques (pharmacologie)</term>
<term>Apoptose (effets des médicaments et des substances chimiques)</term>
<term>Autophagie (effets des médicaments et des substances chimiques)</term>
<term>Carcinome hépatocellulaire (métabolisme)</term>
<term>Cytométrie en flux (MeSH)</term>
<term>Humains (MeSH)</term>
<term>Hypoglycémiants (pharmacologie)</term>
<term>Hétérogreffes (MeSH)</term>
<term>Immunoprécipitation de la chromatine (MeSH)</term>
<term>Lignée cellulaire tumorale (MeSH)</term>
<term>Metformine (pharmacologie)</term>
<term>Microscopie de fluorescence (MeSH)</term>
<term>Mâle (MeSH)</term>
<term>Protéine delta liant les séquences stimulatrices de type CCAAT (métabolisme)</term>
<term>Réaction de polymérisation en chaîne (MeSH)</term>
<term>Souris (MeSH)</term>
<term>Souris SCID (MeSH)</term>
<term>Souris de lignée NOD (MeSH)</term>
<term>Technique de Western (MeSH)</term>
<term>Techniques de knock-down de gènes (MeSH)</term>
<term>Tumeurs du foie (métabolisme)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>CCAAT-Enhancer-Binding Protein-delta</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antineoplastic Agents</term>
<term>Hypoglycemic Agents</term>
<term>Metformin</term>
</keywords>
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<term>Autophagy</term>
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<keywords scheme="MESH" qualifier="effets des médicaments et des substances chimiques" xml:lang="fr"><term>Apoptose</term>
<term>Autophagie</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Carcinoma, Hepatocellular</term>
<term>Liver Neoplasms</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Carcinome hépatocellulaire</term>
<term>Protéine delta liant les séquences stimulatrices de type CCAAT</term>
<term>Tumeurs du foie</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Antinéoplasiques</term>
<term>Hypoglycémiants</term>
<term>Metformine</term>
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<term>Blotting, Western</term>
<term>Cell Line, Tumor</term>
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<term>Flow Cytometry</term>
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<term>Heterografts</term>
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<term>Hétérogreffes</term>
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<term>Microscopie de fluorescence</term>
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<term>Réaction de polymérisation en chaîne</term>
<term>Souris</term>
<term>Souris SCID</term>
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<front><div type="abstract" xml:lang="en">Metformin, as an AMP-activated protein kinase (AMPK) activator, can activate autophagy. A study showed that metformin decreased the risk of hepatocellular carcinoma (HCC) in diabetic patients. However, the detailed mechanism in the metformin-mediated anticancer effect remains an open question. Transcription factor CCAAT/enhancer-binding protein delta (CEBPD) has been suggested to serve as a tumor suppressor and is responsive to multiple anticancer drugs in HCC. In this study, we found that CEBPD and autophagy are involved in metformin-induced cell apoptosis in Huh7 cells. The underlying mechanisms in this process included a reduction in Src-mediated CEBPD protein degradation and an increase in CEBPD-regulated LC3B and ATG3 gene transcription under metformin treatment. We also found that AMPK is involved in metformin-induced CEBPD expression. Combined treatment with metformin and rapamycin can enhance autophagic cell death through the AMPK-dependent and AMPK-independent pathway, respectively. Taken together, we provide a new insight and therapeutic approach by targeting autophagy in the treatment of HCC.</div>
</front>
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<ArticleTitle>Metformin promotes apoptosis in hepatocellular carcinoma through the CEBPD-induced autophagy pathway.</ArticleTitle>
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<Abstract><AbstractText>Metformin, as an AMP-activated protein kinase (AMPK) activator, can activate autophagy. A study showed that metformin decreased the risk of hepatocellular carcinoma (HCC) in diabetic patients. However, the detailed mechanism in the metformin-mediated anticancer effect remains an open question. Transcription factor CCAAT/enhancer-binding protein delta (CEBPD) has been suggested to serve as a tumor suppressor and is responsive to multiple anticancer drugs in HCC. In this study, we found that CEBPD and autophagy are involved in metformin-induced cell apoptosis in Huh7 cells. The underlying mechanisms in this process included a reduction in Src-mediated CEBPD protein degradation and an increase in CEBPD-regulated LC3B and ATG3 gene transcription under metformin treatment. We also found that AMPK is involved in metformin-induced CEBPD expression. Combined treatment with metformin and rapamycin can enhance autophagic cell death through the AMPK-dependent and AMPK-independent pathway, respectively. Taken together, we provide a new insight and therapeutic approach by targeting autophagy in the treatment of HCC.</AbstractText>
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