Trans-scirpusin A showed antitumor effects via autophagy activation and apoptosis induction of colorectal cancer cells.
Identifieur interne : 000703 ( Main/Exploration ); précédent : 000702; suivant : 000704Trans-scirpusin A showed antitumor effects via autophagy activation and apoptosis induction of colorectal cancer cells.
Auteurs : Eun-Hye Hong [Corée du Sud] ; Eun-Young Heo [Corée du Sud] ; Jae-Hyoung Song [Corée du Sud] ; Bo-Eun Kwon [Corée du Sud] ; Jae-Young Lee [Corée du Sud] ; Yaejeong Park [Corée du Sud] ; Jinwoong Kim [Corée du Sud] ; Sun-Young Chang [Corée du Sud] ; Young-Won Chin [Corée du Sud] ; Sang-Min Jeon [Corée du Sud] ; Hyun-Jeong Ko [Corée du Sud]Source :
- Oncotarget [ 1949-2553 ] ; 2017.
Descripteurs français
- KwdFr :
- Animaux (MeSH), Apoptose (effets des médicaments et des substances chimiques), Apoptose (génétique), Autophagie (effets des médicaments et des substances chimiques), Autophagie (génétique), Benzofuranes (administration et posologie), Benzofuranes (composition chimique), Benzofuranes (pharmacologie), Charge tumorale (effets des médicaments et des substances chimiques), Charge tumorale (génétique), Docetaxel (MeSH), Humains (MeSH), Lignée cellulaire tumorale (MeSH), Protocoles de polychimiothérapie antinéoplasique (pharmacologie), Récepteur ErbB-2 (génétique), Régulation de l'expression des gènes tumoraux (effets des médicaments et des substances chimiques), Souris de lignée BALB C (MeSH), Stilbènes (administration et posologie), Stilbènes (composition chimique), Stilbènes (pharmacologie), Structure moléculaire (MeSH), Survie cellulaire (effets des médicaments et des substances chimiques), Survie cellulaire (génétique), Synergie des médicaments (MeSH), Taxoïdes (administration et posologie), Taxoïdes (pharmacologie), Tumeurs colorectales (génétique), Tumeurs colorectales (métabolisme), Tumeurs colorectales (traitement médicamenteux).
- MESH :
- administration et posologie : Benzofuranes, Stilbènes, Taxoïdes.
- composition chimique : Benzofuranes, Stilbènes.
- effets des médicaments et des substances chimiques : Apoptose, Autophagie, Charge tumorale, Régulation de l'expression des gènes tumoraux, Survie cellulaire.
- génétique : Apoptose, Autophagie, Charge tumorale, Récepteur ErbB-2, Survie cellulaire, Tumeurs colorectales.
- métabolisme : Tumeurs colorectales.
- pharmacologie : Benzofuranes, Protocoles de polychimiothérapie antinéoplasique, Stilbènes, Taxoïdes.
- traitement médicamenteux : Tumeurs colorectales.
- Animaux, Docetaxel, Humains, Lignée cellulaire tumorale, Souris de lignée BALB C, Structure moléculaire, Synergie des médicaments.
English descriptors
- KwdEn :
- Animals (MeSH), Antineoplastic Combined Chemotherapy Protocols (pharmacology), Apoptosis (drug effects), Apoptosis (genetics), Autophagy (drug effects), Autophagy (genetics), Benzofurans (administration & dosage), Benzofurans (chemistry), Benzofurans (pharmacology), Cell Line, Tumor (MeSH), Cell Survival (drug effects), Cell Survival (genetics), Colorectal Neoplasms (drug therapy), Colorectal Neoplasms (genetics), Colorectal Neoplasms (metabolism), Docetaxel (MeSH), Drug Synergism (MeSH), Gene Expression Regulation, Neoplastic (drug effects), Humans (MeSH), Mice, Inbred BALB C (MeSH), Molecular Structure (MeSH), Receptor, ErbB-2 (genetics), Stilbenes (administration & dosage), Stilbenes (chemistry), Stilbenes (pharmacology), Taxoids (administration & dosage), Taxoids (pharmacology), Tumor Burden (drug effects), Tumor Burden (genetics).
- MESH :
- chemical , administration & dosage : Benzofurans, Stilbenes, Taxoids.
- chemical , chemistry : Benzofurans, Stilbenes.
- drug effects : Apoptosis, Autophagy, Cell Survival, Gene Expression Regulation, Neoplastic, Tumor Burden.
- drug therapy : Colorectal Neoplasms.
- genetics : Apoptosis, Autophagy, Cell Survival, Colorectal Neoplasms, Receptor, ErbB-2, Tumor Burden.
- metabolism : Colorectal Neoplasms.
- pharmacology : Antineoplastic Combined Chemotherapy Protocols, Benzofurans, Stilbenes, Taxoids.
- Animals, Cell Line, Tumor, Docetaxel, Drug Synergism, Humans, Mice, Inbred BALB C, Molecular Structure.
Abstract
Trans-Scirpusin A (TSA) is a resveratrol oligomer found in Borassus flabellifer L. We found that TSA inhibited the growth of colorectal cancer Her2/CT26 cells in vivo in mice. Although some cytotoxic T lymphocytes (CTLs) were induced against the tumor-associated antigen Her2, TSA treatment did not significantly increase the level of Her2-specific CTL response compared to that with vehicle treatment. However, there was a significant increase in the level of TNF-α mRNA in tumor tissue and Her2-specific Ab (antibody) production. More importantly, we found that TSA overcomes the tumor-associated immunosuppressive microenvironment by reducing the number of CD25+FoxP3+ regulatory T cells and myeloid-derived suppressor cells (MDSCs). We detected the induction of autophagy in TSA-treated Her2/CT26 cells, based on the increased level of the mammalian autophagy protein LC3 puncta, and increased conversion of LC3-I to LC3-II. Further, TSA induced 5' AMP-activated protein kinase (p-AMPK) (T172) and inhibited mammalian target of rapamycin complex 1 (mTORC1) activity as estimated by phosphorylated ribosomal protein S6 kinase beta-1 (p-p70S6K) levels, thereby suggesting that TSA-mediated AMPK activation and inhibition of mTORC1 pathway might be associated with autophagy induction. TSA also induced apoptosis of Her2/CT26 cells, as inferred by the increased sub-G1 mitotic phases in these cells, Annexin V/PI-double positive results, and TUNEL-positive cells. Finally, we found that the combined treatment of mice with docetaxel and TSA successfully inhibited tumor growth to a greater extent than docetaxel alone. Therefore, we propose the use of TSA for supplementary anticancer therapy to support anti-neoplastic drugs, such as docetaxel, by inducing apoptosis in cancer cells and resulting in the induction of neighborhood anti-cancer immunity.
DOI: 10.18632/oncotarget.17388
PubMed: 28489607
PubMed Central: PMC5522333
Affiliations:
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24341</wicri:noRegion></affiliation></author><author><name sortKey="Heo, Eun Young" sort="Heo, Eun Young" uniqKey="Heo E" first="Eun-Young" last="Heo">Eun-Young Heo</name><affiliation wicri:level="1"><nlm:affiliation>Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon, Gangwon-do 24341, Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon, Gangwon-do 24341</wicri:regionArea><wicri:noRegion>Gangwon-do 24341</wicri:noRegion></affiliation></author><author><name sortKey="Song, Jae Hyoung" sort="Song, Jae Hyoung" uniqKey="Song J" first="Jae-Hyoung" last="Song">Jae-Hyoung Song</name><affiliation wicri:level="1"><nlm:affiliation>Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon, Gangwon-do 24341, Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon, Gangwon-do 24341</wicri:regionArea><wicri:noRegion>Gangwon-do 24341</wicri:noRegion></affiliation></author><author><name sortKey="Kwon, Bo Eun" sort="Kwon, Bo Eun" uniqKey="Kwon B" first="Bo-Eun" last="Kwon">Bo-Eun Kwon</name><affiliation wicri:level="1"><nlm:affiliation>Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon, Gangwon-do 24341, Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon, Gangwon-do 24341</wicri:regionArea><wicri:noRegion>Gangwon-do 24341</wicri:noRegion></affiliation></author><author><name sortKey="Lee, Jae Young" sort="Lee, Jae Young" uniqKey="Lee J" first="Jae-Young" last="Lee">Jae-Young Lee</name><affiliation wicri:level="1"><nlm:affiliation>Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon, Gangwon-do 24341, Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon, Gangwon-do 24341</wicri:regionArea><wicri:noRegion>Gangwon-do 24341</wicri:noRegion></affiliation></author><author><name sortKey="Park, Yaejeong" sort="Park, Yaejeong" uniqKey="Park Y" first="Yaejeong" last="Park">Yaejeong Park</name><affiliation wicri:level="4"><nlm:affiliation>College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 08826, Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 08826</wicri:regionArea><orgName type="university">Université nationale de Séoul</orgName><placeName><settlement type="city">Séoul</settlement></placeName></affiliation></author><author><name sortKey="Kim, Jinwoong" sort="Kim, Jinwoong" uniqKey="Kim J" first="Jinwoong" last="Kim">Jinwoong Kim</name><affiliation wicri:level="4"><nlm:affiliation>College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 08826, Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 08826</wicri:regionArea><orgName type="university">Université nationale de Séoul</orgName><placeName><settlement type="city">Séoul</settlement></placeName></affiliation></author><author><name sortKey="Chang, Sun Young" sort="Chang, Sun Young" uniqKey="Chang S" first="Sun-Young" last="Chang">Sun-Young Chang</name><affiliation wicri:level="1"><nlm:affiliation>Laboratory of Microbiology, College of Pharmacy, and Research Institute of Pharmaceutical Science and Technology (RIPST), Ajou University, Suwon, Gyeonggi-do 16499, Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Laboratory of Microbiology, College of Pharmacy, and Research Institute of Pharmaceutical Science and Technology (RIPST), Ajou University, Suwon, Gyeonggi-do 16499</wicri:regionArea><wicri:noRegion>Gyeonggi-do 16499</wicri:noRegion></affiliation></author><author><name sortKey="Chin, Young Won" sort="Chin, Young Won" uniqKey="Chin Y" first="Young-Won" last="Chin">Young-Won Chin</name><affiliation wicri:level="1"><nlm:affiliation>College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University-Seoul, Goyang, Gyeonggi-do 10326, Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University-Seoul, Goyang, Gyeonggi-do 10326</wicri:regionArea><wicri:noRegion>Gyeonggi-do 10326</wicri:noRegion></affiliation></author><author><name sortKey="Jeon, Sang Min" sort="Jeon, Sang Min" uniqKey="Jeon S" first="Sang-Min" last="Jeon">Sang-Min Jeon</name><affiliation wicri:level="1"><nlm:affiliation>Lab of Cancer Signaling and Metabolism Network, College of Pharmacy, and Research Institute of Pharmaceutical Science and Technology (RIPST), Ajou University, Suwon, Gyeonggi-do 16499, Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Lab of Cancer Signaling and Metabolism Network, College of Pharmacy, and Research Institute of Pharmaceutical Science and Technology (RIPST), Ajou University, Suwon, Gyeonggi-do 16499</wicri:regionArea><wicri:noRegion>Gyeonggi-do 16499</wicri:noRegion></affiliation></author><author><name sortKey="Ko, Hyun Jeong" sort="Ko, Hyun Jeong" uniqKey="Ko H" first="Hyun-Jeong" last="Ko">Hyun-Jeong Ko</name><affiliation wicri:level="1"><nlm:affiliation>Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon, Gangwon-do 24341, Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon, Gangwon-do 24341</wicri:regionArea><wicri:noRegion>Gangwon-do 24341</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:affiliation>Convergence Research Center for Functional Plant Products, Advanced Institutes of Convergence Technology, Yeongtong-gu, Suwon, Gyeonggi-do 16229, Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Convergence Research Center for Functional Plant Products, Advanced Institutes of Convergence Technology, Yeongtong-gu, Suwon, Gyeonggi-do 16229</wicri:regionArea><wicri:noRegion>Gyeonggi-do 16229</wicri:noRegion></affiliation></author></analytic><series><title level="j">Oncotarget</title><idno type="eISSN">1949-2553</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals (MeSH)</term><term>Antineoplastic Combined Chemotherapy Protocols (pharmacology)</term><term>Apoptosis (drug effects)</term><term>Apoptosis (genetics)</term><term>Autophagy (drug effects)</term><term>Autophagy (genetics)</term><term>Benzofurans (administration & dosage)</term><term>Benzofurans (chemistry)</term><term>Benzofurans (pharmacology)</term><term>Cell Line, Tumor (MeSH)</term><term>Cell Survival (drug effects)</term><term>Cell Survival (genetics)</term><term>Colorectal Neoplasms (drug therapy)</term><term>Colorectal Neoplasms (genetics)</term><term>Colorectal Neoplasms (metabolism)</term><term>Docetaxel (MeSH)</term><term>Drug Synergism (MeSH)</term><term>Gene Expression Regulation, Neoplastic (drug effects)</term><term>Humans (MeSH)</term><term>Mice, Inbred BALB C (MeSH)</term><term>Molecular Structure (MeSH)</term><term>Receptor, ErbB-2 (genetics)</term><term>Stilbenes (administration & dosage)</term><term>Stilbenes (chemistry)</term><term>Stilbenes (pharmacology)</term><term>Taxoids (administration & dosage)</term><term>Taxoids (pharmacology)</term><term>Tumor Burden (drug effects)</term><term>Tumor Burden (genetics)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux (MeSH)</term><term>Apoptose (effets des médicaments et des substances chimiques)</term><term>Apoptose (génétique)</term><term>Autophagie (effets des médicaments et des substances chimiques)</term><term>Autophagie (génétique)</term><term>Benzofuranes (administration et posologie)</term><term>Benzofuranes (composition chimique)</term><term>Benzofuranes (pharmacologie)</term><term>Charge tumorale (effets des médicaments et des substances chimiques)</term><term>Charge tumorale (génétique)</term><term>Docetaxel (MeSH)</term><term>Humains (MeSH)</term><term>Lignée cellulaire tumorale (MeSH)</term><term>Protocoles de polychimiothérapie antinéoplasique (pharmacologie)</term><term>Récepteur ErbB-2 (génétique)</term><term>Régulation de l'expression des gènes tumoraux (effets des médicaments et des substances chimiques)</term><term>Souris de lignée BALB C (MeSH)</term><term>Stilbènes (administration et posologie)</term><term>Stilbènes (composition chimique)</term><term>Stilbènes (pharmacologie)</term><term>Structure moléculaire (MeSH)</term><term>Survie cellulaire (effets des médicaments et des substances chimiques)</term><term>Survie cellulaire (génétique)</term><term>Synergie des médicaments (MeSH)</term><term>Taxoïdes (administration et posologie)</term><term>Taxoïdes (pharmacologie)</term><term>Tumeurs colorectales (génétique)</term><term>Tumeurs colorectales (métabolisme)</term><term>Tumeurs colorectales (traitement médicamenteux)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Benzofurans</term><term>Stilbenes</term><term>Taxoids</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Benzofurans</term><term>Stilbenes</term></keywords><keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Benzofuranes</term><term>Stilbènes</term><term>Taxoïdes</term></keywords><keywords scheme="MESH" qualifier="composition chimique" xml:lang="fr"><term>Benzofuranes</term><term>Stilbènes</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Apoptosis</term><term>Autophagy</term><term>Cell Survival</term><term>Gene Expression Regulation, Neoplastic</term><term>Tumor Burden</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Colorectal Neoplasms</term></keywords><keywords scheme="MESH" qualifier="effets des médicaments et des substances chimiques" xml:lang="fr"><term>Apoptose</term><term>Autophagie</term><term>Charge tumorale</term><term>Régulation de l'expression des gènes tumoraux</term><term>Survie cellulaire</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Apoptosis</term><term>Autophagy</term><term>Cell Survival</term><term>Colorectal Neoplasms</term><term>Receptor, ErbB-2</term><term>Tumor Burden</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Apoptose</term><term>Autophagie</term><term>Charge tumorale</term><term>Récepteur ErbB-2</term><term>Survie cellulaire</term><term>Tumeurs colorectales</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Colorectal Neoplasms</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Tumeurs colorectales</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Benzofuranes</term><term>Protocoles de polychimiothérapie antinéoplasique</term><term>Stilbènes</term><term>Taxoïdes</term></keywords><keywords scheme="MESH" qualifier="pharmacology" xml:lang="en"><term>Antineoplastic Combined Chemotherapy Protocols</term><term>Benzofurans</term><term>Stilbenes</term><term>Taxoids</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Tumeurs colorectales</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cell Line, Tumor</term><term>Docetaxel</term><term>Drug Synergism</term><term>Humans</term><term>Mice, Inbred BALB C</term><term>Molecular Structure</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Docetaxel</term><term>Humains</term><term>Lignée cellulaire tumorale</term><term>Souris de lignée BALB C</term><term>Structure moléculaire</term><term>Synergie des médicaments</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Trans-Scirpusin A (TSA) is a resveratrol oligomer found in Borassus flabellifer L. We found that TSA inhibited the growth of colorectal cancer Her2/CT26 cells in vivo in mice. Although some cytotoxic T lymphocytes (CTLs) were induced against the tumor-associated antigen Her2, TSA treatment did not significantly increase the level of Her2-specific CTL response compared to that with vehicle treatment. However, there was a significant increase in the level of TNF-α mRNA in tumor tissue and Her2-specific Ab (antibody) production. More importantly, we found that TSA overcomes the tumor-associated immunosuppressive microenvironment by reducing the number of CD25+FoxP3+ regulatory T cells and myeloid-derived suppressor cells (MDSCs). We detected the induction of autophagy in TSA-treated Her2/CT26 cells, based on the increased level of the mammalian autophagy protein LC3 puncta, and increased conversion of LC3-I to LC3-II. Further, TSA induced 5' AMP-activated protein kinase (p-AMPK) (T172) and inhibited mammalian target of rapamycin complex 1 (mTORC1) activity as estimated by phosphorylated ribosomal protein S6 kinase beta-1 (p-p70S6K) levels, thereby suggesting that TSA-mediated AMPK activation and inhibition of mTORC1 pathway might be associated with autophagy induction. TSA also induced apoptosis of Her2/CT26 cells, as inferred by the increased sub-G1 mitotic phases in these cells, Annexin V/PI-double positive results, and TUNEL-positive cells. Finally, we found that the combined treatment of mice with docetaxel and TSA successfully inhibited tumor growth to a greater extent than docetaxel alone. Therefore, we propose the use of TSA for supplementary anticancer therapy to support anti-neoplastic drugs, such as docetaxel, by inducing apoptosis in cancer cells and resulting in the induction of neighborhood anti-cancer immunity.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">28489607</PMID><DateCompleted><Year>2018</Year><Month>04</Month><Day>09</Day></DateCompleted><DateRevised><Year>2018</Year><Month>12</Month><Day>02</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1949-2553</ISSN><JournalIssue CitedMedium="Internet"><Volume>8</Volume><Issue>25</Issue><PubDate><Year>2017</Year><Month>Jun</Month><Day>20</Day></PubDate></JournalIssue><Title>Oncotarget</Title><ISOAbbreviation>Oncotarget</ISOAbbreviation></Journal><ArticleTitle>Trans-scirpusin A showed antitumor effects via autophagy activation and apoptosis induction of colorectal cancer cells.</ArticleTitle><Pagination><MedlinePgn>41401-41411</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.18632/oncotarget.17388</ELocationID><Abstract><AbstractText>Trans-Scirpusin A (TSA) is a resveratrol oligomer found in Borassus flabellifer L. We found that TSA inhibited the growth of colorectal cancer Her2/CT26 cells in vivo in mice. Although some cytotoxic T lymphocytes (CTLs) were induced against the tumor-associated antigen Her2, TSA treatment did not significantly increase the level of Her2-specific CTL response compared to that with vehicle treatment. However, there was a significant increase in the level of TNF-α mRNA in tumor tissue and Her2-specific Ab (antibody) production. More importantly, we found that TSA overcomes the tumor-associated immunosuppressive microenvironment by reducing the number of CD25+FoxP3+ regulatory T cells and myeloid-derived suppressor cells (MDSCs). We detected the induction of autophagy in TSA-treated Her2/CT26 cells, based on the increased level of the mammalian autophagy protein LC3 puncta, and increased conversion of LC3-I to LC3-II. Further, TSA induced 5' AMP-activated protein kinase (p-AMPK) (T172) and inhibited mammalian target of rapamycin complex 1 (mTORC1) activity as estimated by phosphorylated ribosomal protein S6 kinase beta-1 (p-p70S6K) levels, thereby suggesting that TSA-mediated AMPK activation and inhibition of mTORC1 pathway might be associated with autophagy induction. TSA also induced apoptosis of Her2/CT26 cells, as inferred by the increased sub-G1 mitotic phases in these cells, Annexin V/PI-double positive results, and TUNEL-positive cells. Finally, we found that the combined treatment of mice with docetaxel and TSA successfully inhibited tumor growth to a greater extent than docetaxel alone. Therefore, we propose the use of TSA for supplementary anticancer therapy to support anti-neoplastic drugs, such as docetaxel, by inducing apoptosis in cancer cells and resulting in the induction of neighborhood anti-cancer immunity.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Hong</LastName><ForeName>Eun-Hye</ForeName><Initials>EH</Initials><AffiliationInfo><Affiliation>Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon, Gangwon-do 24341, Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Heo</LastName><ForeName>Eun-Young</ForeName><Initials>EY</Initials><AffiliationInfo><Affiliation>Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon, Gangwon-do 24341, Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Song</LastName><ForeName>Jae-Hyoung</ForeName><Initials>JH</Initials><AffiliationInfo><Affiliation>Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon, Gangwon-do 24341, Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kwon</LastName><ForeName>Bo-Eun</ForeName><Initials>BE</Initials><AffiliationInfo><Affiliation>Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon, Gangwon-do 24341, Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lee</LastName><ForeName>Jae-Young</ForeName><Initials>JY</Initials><AffiliationInfo><Affiliation>Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon, Gangwon-do 24341, Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Park</LastName><ForeName>Yaejeong</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 08826, Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kim</LastName><ForeName>Jinwoong</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 08826, Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chang</LastName><ForeName>Sun-Young</ForeName><Initials>SY</Initials><AffiliationInfo><Affiliation>Laboratory of Microbiology, College of Pharmacy, and Research Institute of Pharmaceutical Science and Technology (RIPST), Ajou University, Suwon, Gyeonggi-do 16499, Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chin</LastName><ForeName>Young-Won</ForeName><Initials>YW</Initials><AffiliationInfo><Affiliation>College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University-Seoul, Goyang, Gyeonggi-do 10326, Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jeon</LastName><ForeName>Sang-Min</ForeName><Initials>SM</Initials><AffiliationInfo><Affiliation>Lab of Cancer Signaling and Metabolism Network, College of Pharmacy, and Research Institute of Pharmaceutical Science and Technology (RIPST), Ajou University, Suwon, Gyeonggi-do 16499, Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ko</LastName><ForeName>Hyun-Jeong</ForeName><Initials>HJ</Initials><AffiliationInfo><Affiliation>Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon, Gangwon-do 24341, Korea.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Convergence Research Center for Functional Plant Products, Advanced Institutes of Convergence Technology, Yeongtong-gu, Suwon, Gyeonggi-do 16229, Korea.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Oncotarget</MedlineTA><NlmUniqueID>101532965</NlmUniqueID><ISSNLinking>1949-2553</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D001572">Benzofurans</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D013267">Stilbenes</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D043823">Taxoids</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C550387">scirpusin A</NameOfSubstance></Chemical><Chemical><RegistryNumber>15H5577CQD</RegistryNumber><NameOfSubstance UI="D000077143">Docetaxel</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.10.1</RegistryNumber><NameOfSubstance UI="C508053">ERBB2 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.10.1</RegistryNumber><NameOfSubstance UI="D018719">Receptor, ErbB-2</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000971" MajorTopicYN="N">Antineoplastic Combined Chemotherapy Protocols</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D017209" MajorTopicYN="N">Apoptosis</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001343" MajorTopicYN="N">Autophagy</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001572" MajorTopicYN="N">Benzofurans</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName><QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D045744" MajorTopicYN="N">Cell Line, Tumor</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002470" MajorTopicYN="N">Cell Survival</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D015179" MajorTopicYN="N">Colorectal Neoplasms</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000077143" MajorTopicYN="N">Docetaxel</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004357" MajorTopicYN="N">Drug Synergism</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015972" MajorTopicYN="N">Gene Expression Regulation, Neoplastic</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008807" MajorTopicYN="N">Mice, Inbred BALB C</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015394" MajorTopicYN="N">Molecular Structure</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018719" MajorTopicYN="N">Receptor, ErbB-2</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D013267" MajorTopicYN="N">Stilbenes</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName><QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D043823" MajorTopicYN="N">Taxoids</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D047368" MajorTopicYN="N">Tumor Burden</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">AMPK</Keyword><Keyword MajorTopicYN="N">apoptosis</Keyword><Keyword MajorTopicYN="N">autophagy</Keyword><Keyword MajorTopicYN="N">colorectal cancer cells</Keyword><Keyword MajorTopicYN="N">trans-scirpusin A</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2017</Year><Month>01</Month><Day>04</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2017</Year><Month>03</Month><Day>30</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2017</Year><Month>5</Month><Day>11</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2018</Year><Month>4</Month><Day>10</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate 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Sang Min" uniqKey="Jeon S" first="Sang-Min" last="Jeon">Sang-Min Jeon</name><name sortKey="Kim, Jinwoong" sort="Kim, Jinwoong" uniqKey="Kim J" first="Jinwoong" last="Kim">Jinwoong Kim</name><name sortKey="Ko, Hyun Jeong" sort="Ko, Hyun Jeong" uniqKey="Ko H" first="Hyun-Jeong" last="Ko">Hyun-Jeong Ko</name><name sortKey="Ko, Hyun Jeong" sort="Ko, Hyun Jeong" uniqKey="Ko H" first="Hyun-Jeong" last="Ko">Hyun-Jeong Ko</name><name sortKey="Kwon, Bo Eun" sort="Kwon, Bo Eun" uniqKey="Kwon B" first="Bo-Eun" last="Kwon">Bo-Eun Kwon</name><name sortKey="Lee, Jae Young" sort="Lee, Jae Young" uniqKey="Lee J" first="Jae-Young" last="Lee">Jae-Young Lee</name><name sortKey="Park, Yaejeong" sort="Park, Yaejeong" uniqKey="Park Y" first="Yaejeong" last="Park">Yaejeong Park</name><name sortKey="Song, Jae Hyoung" sort="Song, Jae Hyoung" uniqKey="Song J" first="Jae-Hyoung" last="Song">Jae-Hyoung Song</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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