Antitumor effects of deguelin on H460 human lung cancer cells in vitro and in vivo: Roles of apoptotic cell death and H460 tumor xenografts model.
Identifieur interne : 000130 ( Main/Exploration ); précédent : 000129; suivant : 000131Antitumor effects of deguelin on H460 human lung cancer cells in vitro and in vivo: Roles of apoptotic cell death and H460 tumor xenografts model.
Auteurs : Yu-Chieh Hsu [Taïwan] ; Jo-Hua Chiang [Taïwan] ; Chun-Shu Yu [Taïwan] ; Te-Chun Hsia [Taïwan] ; Rick Sai-Chuen Wu [Taïwan] ; Jin-Cherng Lien [Taïwan] ; Kuang-Chi Lai [Taïwan] ; Fu-Shun Yu [Taïwan] ; Jing-Gung Chung [Taïwan]Source :
- Environmental toxicology [ 1522-7278 ] ; 2017.
Descripteurs français
- KwdFr :
- Altération de l'ADN (MeSH), Animaux (MeSH), Anticarcinogènes (pharmacologie), Apoptose (effets des médicaments et des substances chimiques), Calcium (métabolisme), Caspase-3 (métabolisme), Humains (MeSH), Lignée cellulaire tumorale (MeSH), Protéines régulatrices de l'apoptose (effets des médicaments et des substances chimiques), Relation dose-effet des médicaments (MeSH), Roténone (analogues et dérivés), Roténone (pharmacologie), Souris (MeSH), Souris de lignée BALB C (MeSH), Souris nude (MeSH), Survie cellulaire (MeSH), Test des comètes (MeSH), Tests d'activité antitumorale sur modèle de xénogreffe (MeSH), Tumeurs du poumon (anatomopathologie), Tumeurs du poumon (traitement médicamenteux).
- MESH :
- analogues et dérivés : Roténone.
- anatomopathologie : Tumeurs du poumon.
- effets des médicaments et des substances chimiques : Apoptose, Protéines régulatrices de l'apoptose.
- métabolisme : Calcium, Caspase-3.
- pharmacologie : Anticarcinogènes, Roténone.
- traitement médicamenteux : Tumeurs du poumon.
- Altération de l'ADN, Animaux, Humains, Lignée cellulaire tumorale, Relation dose-effet des médicaments, Souris, Souris de lignée BALB C, Souris nude, Survie cellulaire, Test des comètes, Tests d'activité antitumorale sur modèle de xénogreffe.
English descriptors
- KwdEn :
- Animals (MeSH), Anticarcinogenic Agents (pharmacology), Apoptosis (drug effects), Apoptosis Regulatory Proteins (drug effects), Calcium (metabolism), Caspase 3 (metabolism), Cell Line, Tumor (MeSH), Cell Survival (MeSH), Comet Assay (MeSH), DNA Damage (MeSH), Dose-Response Relationship, Drug (MeSH), Humans (MeSH), Lung Neoplasms (drug therapy), Lung Neoplasms (pathology), Mice (MeSH), Mice, Inbred BALB C (MeSH), Mice, Nude (MeSH), Rotenone (analogs & derivatives), Rotenone (pharmacology), Xenograft Model Antitumor Assays (MeSH).
- MESH :
- chemical , analogs & derivatives : Rotenone.
- chemical , drug effects : Apoptosis Regulatory Proteins.
- chemical , metabolism : Calcium, Caspase 3.
- chemical , pharmacology : Anticarcinogenic Agents, Rotenone.
- drug effects : Apoptosis.
- drug therapy : Lung Neoplasms.
- pathology : Lung Neoplasms.
- Animals, Cell Line, Tumor, Cell Survival, Comet Assay, DNA Damage, Dose-Response Relationship, Drug, Humans, Mice, Mice, Inbred BALB C, Mice, Nude, Xenograft Model Antitumor Assays.
Abstract
Deguelin, a naturally occurring rotenoid of the flavonoid family, is known to be an Akt inhibitor, to have chemopreventive activities and anti-tumor effect on several cancers. In this study, investigation to elucidate the effect of deguelin on apoptotic pathways in human lung cancer cells and on the anti-tumor effect in lung cancer xenograft nu/nu mice was performed. In vitro studies, found that deguelin induced cell morphological changes, and decreased the percentage of viability through the induction of apoptosis in H460 lung cancer cells. Deguelin triggered apoptosis in H460 cells was also confirmed by DAPI staining, DNA gel electrophoresis, and Annexin V-FITC staining and these effects are dose-dependent manners. It was also found that deguelin promoted the Ca2+ production and activation of caspase-3 but decreased the level of ΔΨm in H460 cells. Western blots indicated that the protein levels of cytochrome c, AIF, and pro-apoptotic Bax and Bak protein were increased, but the anti-apoptotic Bcl-2 and Bcl-x were decreased that may have led to apoptosis in H460 cells after exposure to deguelin. It was also confirmed by confocal laser microscope examination that deguelin promoted the release of AIF from mitochondria to cytosol. In vivo studies, found that in immunodeficient nu/nu mice bearing H460 tumor xenografts showed that the deguelin significantly suppressed tumor growth. Deguelin might be a potential therapeutic agent for the treatment of lung cancer in the future. This finding might fully support a critical event for deguelin via induction of apoptotic cell death and H460 tumor xenografts model against human lung cancer. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 84-98, 2017.
DOI: 10.1002/tox.22214
PubMed: 26592500
Affiliations:
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Chuen" uniqKey="Wu R" first="Rick Sai-Chuen" last="Wu">Rick Sai-Chuen Wu</name><affiliation wicri:level="1"><nlm:affiliation>Department of Anesthesiology, China Medical University Hospital, Taichung, 404, Taiwan.</nlm:affiliation><country xml:lang="fr">Taïwan</country><wicri:regionArea>Department of Anesthesiology, China Medical University Hospital, Taichung, 404</wicri:regionArea><wicri:noRegion>404</wicri:noRegion></affiliation></author><author><name sortKey="Lien, Jin Cherng" sort="Lien, Jin Cherng" uniqKey="Lien J" first="Jin-Cherng" last="Lien">Jin-Cherng Lien</name><affiliation wicri:level="1"><nlm:affiliation>School of Pharmacy, China Medical University, Taichung, 404, Taiwan.</nlm:affiliation><country xml:lang="fr">Taïwan</country><wicri:regionArea>School of Pharmacy, China Medical University, Taichung, 404</wicri:regionArea><wicri:noRegion>404</wicri:noRegion></affiliation></author><author><name sortKey="Lai, Kuang Chi" sort="Lai, Kuang Chi" uniqKey="Lai K" first="Kuang-Chi" last="Lai">Kuang-Chi Lai</name><affiliation wicri:level="1"><nlm:affiliation>School of Medicine, China Medical University Hospital, Taichung, 404, Taiwan.</nlm:affiliation><country xml:lang="fr">Taïwan</country><wicri:regionArea>School of Medicine, China Medical University Hospital, Taichung, 404</wicri:regionArea><wicri:noRegion>404</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:affiliation>Department of Surgery, China Medical University Beigang Hospital, Yunlin, 651, Taiwan.</nlm:affiliation><country xml:lang="fr">Taïwan</country><wicri:regionArea>Department of Surgery, China Medical University Beigang Hospital, Yunlin, 651</wicri:regionArea><wicri:noRegion>651</wicri:noRegion></affiliation></author><author><name sortKey="Yu, Fu Shun" sort="Yu, Fu Shun" uniqKey="Yu F" first="Fu-Shun" last="Yu">Fu-Shun Yu</name><affiliation wicri:level="1"><nlm:affiliation>School of Dentist, China Medical University, Taichung, 404, Taiwan.</nlm:affiliation><country xml:lang="fr">Taïwan</country><wicri:regionArea>School of Dentist, China Medical University, Taichung, 404</wicri:regionArea><wicri:noRegion>404</wicri:noRegion></affiliation></author><author><name sortKey="Chung, Jing Gung" sort="Chung, Jing Gung" uniqKey="Chung J" first="Jing-Gung" last="Chung">Jing-Gung Chung</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biological Science and Technology, China Medical University, Taichung, 404, Taiwan.</nlm:affiliation><country xml:lang="fr">Taïwan</country><wicri:regionArea>Department of Biological Science and Technology, China Medical University, Taichung, 404</wicri:regionArea><wicri:noRegion>404</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:affiliation>Department of Biotechnology, Asia University, Taichung, 413, Taiwan.</nlm:affiliation><country xml:lang="fr">Taïwan</country><wicri:regionArea>Department of Biotechnology, Asia University, Taichung, 413</wicri:regionArea><wicri:noRegion>413</wicri:noRegion></affiliation></author></analytic><series><title level="j">Environmental toxicology</title><idno type="eISSN">1522-7278</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>Anticarcinogenic Agents (pharmacology)</term><term>Apoptosis (drug effects)</term><term>Apoptosis Regulatory Proteins (drug effects)</term><term>Calcium (metabolism)</term><term>Caspase 3 (metabolism)</term><term>Cell Line, Tumor (MeSH)</term><term>Cell Survival (MeSH)</term><term>Comet Assay (MeSH)</term><term>DNA Damage (MeSH)</term><term>Dose-Response Relationship, Drug (MeSH)</term><term>Humans (MeSH)</term><term>Lung Neoplasms (drug therapy)</term><term>Lung Neoplasms (pathology)</term><term>Mice (MeSH)</term><term>Mice, Inbred BALB C (MeSH)</term><term>Mice, Nude (MeSH)</term><term>Rotenone (analogs & derivatives)</term><term>Rotenone (pharmacology)</term><term>Xenograft Model Antitumor Assays (MeSH)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Altération de l'ADN (MeSH)</term><term>Animaux (MeSH)</term><term>Anticarcinogènes (pharmacologie)</term><term>Apoptose (effets des médicaments et des substances chimiques)</term><term>Calcium (métabolisme)</term><term>Caspase-3 (métabolisme)</term><term>Humains (MeSH)</term><term>Lignée cellulaire tumorale (MeSH)</term><term>Protéines régulatrices de l'apoptose (effets des médicaments et des substances chimiques)</term><term>Relation dose-effet des médicaments (MeSH)</term><term>Roténone (analogues et dérivés)</term><term>Roténone (pharmacologie)</term><term>Souris (MeSH)</term><term>Souris de lignée BALB C (MeSH)</term><term>Souris nude (MeSH)</term><term>Survie cellulaire (MeSH)</term><term>Test des comètes (MeSH)</term><term>Tests d'activité antitumorale sur modèle de xénogreffe (MeSH)</term><term>Tumeurs du poumon (anatomopathologie)</term><term>Tumeurs du poumon (traitement médicamenteux)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>Rotenone</term></keywords><keywords scheme="MESH" type="chemical" qualifier="drug effects" xml:lang="en"><term>Apoptosis Regulatory Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Calcium</term><term>Caspase 3</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Anticarcinogenic Agents</term><term>Rotenone</term></keywords><keywords scheme="MESH" qualifier="analogues et dérivés" xml:lang="fr"><term>Roténone</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Tumeurs du poumon</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Apoptosis</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Lung Neoplasms</term></keywords><keywords scheme="MESH" qualifier="effets des médicaments et des substances chimiques" xml:lang="fr"><term>Apoptose</term><term>Protéines régulatrices de l'apoptose</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Calcium</term><term>Caspase-3</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Lung Neoplasms</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Anticarcinogènes</term><term>Roténone</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Tumeurs du poumon</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cell Line, Tumor</term><term>Cell Survival</term><term>Comet Assay</term><term>DNA Damage</term><term>Dose-Response Relationship, Drug</term><term>Humans</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Mice, Nude</term><term>Xenograft Model Antitumor Assays</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Altération de l'ADN</term><term>Animaux</term><term>Humains</term><term>Lignée cellulaire tumorale</term><term>Relation dose-effet des médicaments</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Souris nude</term><term>Survie cellulaire</term><term>Test des comètes</term><term>Tests d'activité antitumorale sur modèle de xénogreffe</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Deguelin, a naturally occurring rotenoid of the flavonoid family, is known to be an Akt inhibitor, to have chemopreventive activities and anti-tumor effect on several cancers. In this study, investigation to elucidate the effect of deguelin on apoptotic pathways in human lung cancer cells and on the anti-tumor effect in lung cancer xenograft nu/nu mice was performed. In vitro studies, found that deguelin induced cell morphological changes, and decreased the percentage of viability through the induction of apoptosis in H460 lung cancer cells. Deguelin triggered apoptosis in H460 cells was also confirmed by DAPI staining, DNA gel electrophoresis, and Annexin V-FITC staining and these effects are dose-dependent manners. It was also found that deguelin promoted the Ca<sup>2+</sup> production and activation of caspase-3 but decreased the level of ΔΨ<sub>m</sub> in H460 cells. Western blots indicated that the protein levels of cytochrome c, AIF, and pro-apoptotic Bax and Bak protein were increased, but the anti-apoptotic Bcl-2 and Bcl-x were decreased that may have led to apoptosis in H460 cells after exposure to deguelin. It was also confirmed by confocal laser microscope examination that deguelin promoted the release of AIF from mitochondria to cytosol. In vivo studies, found that in immunodeficient nu/nu mice bearing H460 tumor xenografts showed that the deguelin significantly suppressed tumor growth. Deguelin might be a potential therapeutic agent for the treatment of lung cancer in the future. This finding might fully support a critical event for deguelin via induction of apoptotic cell death and H460 tumor xenografts model against human lung cancer. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 84-98, 2017.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" IndexingMethod="Curated" Owner="NLM"><PMID Version="1">26592500</PMID><DateCompleted><Year>2017</Year><Month>03</Month><Day>02</Day></DateCompleted><DateRevised><Year>2018</Year><Month>12</Month><Day>02</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1522-7278</ISSN><JournalIssue CitedMedium="Internet"><Volume>32</Volume><Issue>1</Issue><PubDate><Year>2017</Year><Month>Jan</Month></PubDate></JournalIssue><Title>Environmental toxicology</Title><ISOAbbreviation>Environ Toxicol</ISOAbbreviation></Journal><ArticleTitle>Antitumor effects of deguelin on H460 human lung cancer cells in vitro and in vivo: Roles of apoptotic cell death and H460 tumor xenografts model.</ArticleTitle><Pagination><MedlinePgn>84-98</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1002/tox.22214</ELocationID><Abstract><AbstractText>Deguelin, a naturally occurring rotenoid of the flavonoid family, is known to be an Akt inhibitor, to have chemopreventive activities and anti-tumor effect on several cancers. In this study, investigation to elucidate the effect of deguelin on apoptotic pathways in human lung cancer cells and on the anti-tumor effect in lung cancer xenograft nu/nu mice was performed. In vitro studies, found that deguelin induced cell morphological changes, and decreased the percentage of viability through the induction of apoptosis in H460 lung cancer cells. Deguelin triggered apoptosis in H460 cells was also confirmed by DAPI staining, DNA gel electrophoresis, and Annexin V-FITC staining and these effects are dose-dependent manners. It was also found that deguelin promoted the Ca<sup>2+</sup> production and activation of caspase-3 but decreased the level of ΔΨ<sub>m</sub> in H460 cells. Western blots indicated that the protein levels of cytochrome c, AIF, and pro-apoptotic Bax and Bak protein were increased, but the anti-apoptotic Bcl-2 and Bcl-x were decreased that may have led to apoptosis in H460 cells after exposure to deguelin. It was also confirmed by confocal laser microscope examination that deguelin promoted the release of AIF from mitochondria to cytosol. In vivo studies, found that in immunodeficient nu/nu mice bearing H460 tumor xenografts showed that the deguelin significantly suppressed tumor growth. Deguelin might be a potential therapeutic agent for the treatment of lung cancer in the future. This finding might fully support a critical event for deguelin via induction of apoptotic cell death and H460 tumor xenografts model against human lung cancer. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 84-98, 2017.</AbstractText><CopyrightInformation>© 2015 Wiley Periodicals, Inc.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Hsu</LastName><ForeName>Yu-Chieh</ForeName><Initials>YC</Initials><AffiliationInfo><Affiliation>Department of Biological Science and Technology, China Medical University, Taichung, 404, Taiwan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chiang</LastName><ForeName>Jo-Hua</ForeName><Initials>JH</Initials><AffiliationInfo><Affiliation>Department of Nursing, Chung-Jen Junior College of Nursing, Health Sciences and Management, Chiayi County, 62241, Taiwan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yu</LastName><ForeName>Chun-Shu</ForeName><Initials>CS</Initials><AffiliationInfo><Affiliation>School of Pharmacy, China Medical University, Taichung, 404, Taiwan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hsia</LastName><ForeName>Te-Chun</ForeName><Initials>TC</Initials><AffiliationInfo><Affiliation>Graduate Institute of Chinese Medicine, China Medical University, Taichung, 404, Taiwan.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wu</LastName><ForeName>Rick Sai-Chuen</ForeName><Initials>RS</Initials><AffiliationInfo><Affiliation>Department of Anesthesiology, China Medical University Hospital, Taichung, 404, Taiwan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lien</LastName><ForeName>Jin-Cherng</ForeName><Initials>JC</Initials><AffiliationInfo><Affiliation>School of Pharmacy, China Medical University, Taichung, 404, Taiwan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lai</LastName><ForeName>Kuang-Chi</ForeName><Initials>KC</Initials><AffiliationInfo><Affiliation>School of Medicine, China Medical University Hospital, Taichung, 404, Taiwan.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Surgery, China Medical University Beigang Hospital, Yunlin, 651, Taiwan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yu</LastName><ForeName>Fu-Shun</ForeName><Initials>FS</Initials><AffiliationInfo><Affiliation>School of Dentist, China Medical University, Taichung, 404, Taiwan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chung</LastName><ForeName>Jing-Gung</ForeName><Initials>JG</Initials><AffiliationInfo><Affiliation>Department of Biological Science and Technology, China Medical University, Taichung, 404, Taiwan.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Biotechnology, Asia University, Taichung, 413, Taiwan.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2015</Year><Month>11</Month><Day>23</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Environ Toxicol</MedlineTA><NlmUniqueID>100885357</NlmUniqueID><ISSNLinking>1520-4081</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D016588">Anticarcinogenic Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D051017">Apoptosis Regulatory Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>03L9OT429T</RegistryNumber><NameOfSubstance UI="D012402">Rotenone</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 3.4.22.-</RegistryNumber><NameOfSubstance UI="C505409">Casp3 protein, mouse</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 3.4.22.-</RegistryNumber><NameOfSubstance UI="D053148">Caspase 3</NameOfSubstance></Chemical><Chemical><RegistryNumber>K5Z93K66IE</RegistryNumber><NameOfSubstance UI="C107676">deguelin</NameOfSubstance></Chemical><Chemical><RegistryNumber>SY7Q814VUP</RegistryNumber><NameOfSubstance UI="D002118">Calcium</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016588" MajorTopicYN="N">Anticarcinogenic Agents</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D017209" MajorTopicYN="N">Apoptosis</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D051017" MajorTopicYN="N">Apoptosis Regulatory Proteins</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002118" MajorTopicYN="N">Calcium</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D053148" MajorTopicYN="N">Caspase 3</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D045744" MajorTopicYN="N">Cell Line, Tumor</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002470" MajorTopicYN="N">Cell Survival</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D020552" MajorTopicYN="N">Comet Assay</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004249" MajorTopicYN="N">DNA Damage</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004305" MajorTopicYN="N">Dose-Response Relationship, Drug</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008175" MajorTopicYN="N">Lung Neoplasms</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName><QualifierName UI="Q000473" MajorTopicYN="Y">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008807" MajorTopicYN="N">Mice, Inbred BALB C</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008819" MajorTopicYN="N">Mice, Nude</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012402" MajorTopicYN="N">Rotenone</DescriptorName><QualifierName UI="Q000031" MajorTopicYN="Y">analogs & derivatives</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D023041" MajorTopicYN="N">Xenograft Model Antitumor Assays</DescriptorName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="Y">H460 human lung cancer cells</Keyword><Keyword MajorTopicYN="Y">apoptosis</Keyword><Keyword MajorTopicYN="Y">deguelin</Keyword><Keyword MajorTopicYN="Y">mitochondria dysfunction</Keyword><Keyword MajorTopicYN="Y">xenograft tumor</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2015</Year><Month>05</Month><Day>04</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2015</Year><Month>10</Month><Day>16</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2015</Year><Month>10</Month><Day>18</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2015</Year><Month>11</Month><Day>26</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2017</Year><Month>3</Month><Day>3</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2015</Year><Month>11</Month><Day>24</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">26592500</ArticleId><ArticleId IdType="doi">10.1002/tox.22214</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Taïwan</li></country></list><tree><country name="Taïwan"><noRegion><name sortKey="Hsu, Yu Chieh" sort="Hsu, Yu Chieh" uniqKey="Hsu Y" first="Yu-Chieh" last="Hsu">Yu-Chieh Hsu</name></noRegion><name sortKey="Chiang, Jo Hua" sort="Chiang, Jo Hua" uniqKey="Chiang J" first="Jo-Hua" last="Chiang">Jo-Hua Chiang</name><name sortKey="Chung, Jing Gung" sort="Chung, Jing Gung" uniqKey="Chung J" first="Jing-Gung" last="Chung">Jing-Gung Chung</name><name sortKey="Chung, Jing Gung" sort="Chung, Jing Gung" uniqKey="Chung J" first="Jing-Gung" last="Chung">Jing-Gung Chung</name><name sortKey="Hsia, Te Chun" sort="Hsia, Te Chun" uniqKey="Hsia T" first="Te-Chun" last="Hsia">Te-Chun Hsia</name><name sortKey="Hsia, Te Chun" sort="Hsia, Te Chun" uniqKey="Hsia T" first="Te-Chun" last="Hsia">Te-Chun Hsia</name><name sortKey="Lai, Kuang Chi" sort="Lai, Kuang Chi" uniqKey="Lai K" first="Kuang-Chi" last="Lai">Kuang-Chi Lai</name><name sortKey="Lai, Kuang Chi" sort="Lai, Kuang Chi" uniqKey="Lai K" first="Kuang-Chi" last="Lai">Kuang-Chi Lai</name><name sortKey="Lien, Jin Cherng" sort="Lien, Jin Cherng" uniqKey="Lien J" first="Jin-Cherng" last="Lien">Jin-Cherng Lien</name><name sortKey="Wu, Rick Sai Chuen" sort="Wu, Rick Sai Chuen" uniqKey="Wu R" first="Rick Sai-Chuen" last="Wu">Rick Sai-Chuen Wu</name><name sortKey="Yu, Chun Shu" sort="Yu, Chun Shu" uniqKey="Yu C" first="Chun-Shu" last="Yu">Chun-Shu Yu</name><name sortKey="Yu, Fu Shun" sort="Yu, Fu Shun" uniqKey="Yu F" first="Fu-Shun" last="Yu">Fu-Shun 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