Chloroquine inhibits cell growth in human A549 lung cancer cells by blocking autophagy and inducing mitochondrial‑mediated apoptosis.
Identifieur interne : 000115 ( PubMed/Corpus ); précédent : 000114; suivant : 000116Chloroquine inhibits cell growth in human A549 lung cancer cells by blocking autophagy and inducing mitochondrial‑mediated apoptosis.
Auteurs : Likun Liu ; Cuicui Han ; Haitao Yu ; Wenbin Zhu ; Hongxia Cui ; Lihong Zheng ; Chunjing Zhang ; Liling YueSource :
- Oncology reports [ 1791-2431 ] ; 2018.
English descriptors
- KwdEn :
- A549 Cells, Autophagy (drug effects), Cell Proliferation (drug effects), Cell Survival (drug effects), Chloroquine (pharmacology), Dose-Response Relationship, Drug, Humans, Lung Neoplasms (drug therapy), Lung Neoplasms (metabolism), Membrane Potential, Mitochondrial (drug effects), Mitochondria (drug effects), Mitochondria (metabolism), Phosphatidylinositol 3-Kinases (metabolism), Proto-Oncogene Proteins c-akt (metabolism), Signal Transduction (drug effects).
- MESH :
- chemical , metabolism : Phosphatidylinositol 3-Kinases, Proto-Oncogene Proteins c-akt.
- chemical , pharmacology : Chloroquine.
- drug effects : Autophagy, Cell Proliferation, Cell Survival, Membrane Potential, Mitochondrial, Mitochondria, Signal Transduction.
- drug therapy : Lung Neoplasms.
- metabolism : Lung Neoplasms, Mitochondria.
- A549 Cells, Dose-Response Relationship, Drug, Humans.
Abstract
Chloroquine (CQ) has been revealed to exhibit antitumor activity in several human tumors including lung cancer as mono‑ or add‑on therapy. The antitumor effect of CQ appears to depend on the tumor type, stage and genetic context. Few studies have focused on the mechanism concerning the antitumor effect of CQ monotherapy and the cause and effect relationship among autophagy, apoptosis and CQ in human lung A549 cells. Therefore, the present study aimed to identify the antitumor effect of CQ monotherapy and analyze the possible mechanism. In the present study, we demonstrated that CQ suppressed human A549 cell growth in a dose‑ and time‑dependent manner. CQ‑mediated growth inhibition in A549 cells was characterized by the targeting of the PI3K/AKT pathway, thus, inducing mitochondria‑mediated apoptosis at relatively higher concentrations by downregulating Bcl‑2 expression, increasing the expression level of Bax, decreasing mitochondrial membrane potential, releasing cytochrome c from the mitochondria into the cytosol, activating caspase‑3 and cleaving PARP. Collectively, these findings may offer a new rationale for using CQ as a lung cancer therapy drug in clinical practice.
DOI: 10.3892/or.2018.6363
PubMed: 29658606
Links to Exploration step
pubmed:29658606Le document en format XML
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China.</nlm:affiliation></affiliation></author><author><name sortKey="Yu, Haitao" sort="Yu, Haitao" uniqKey="Yu H" first="Haitao" last="Yu">Haitao Yu</name><affiliation><nlm:affiliation>Department of Biology Genetics, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China.</nlm:affiliation></affiliation></author><author><name sortKey="Zhu, Wenbin" sort="Zhu, Wenbin" uniqKey="Zhu W" first="Wenbin" last="Zhu">Wenbin Zhu</name><affiliation><nlm:affiliation>Research Institute of Medicine and Pharmacy, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China.</nlm:affiliation></affiliation></author><author><name sortKey="Cui, Hongxia" sort="Cui, Hongxia" uniqKey="Cui H" first="Hongxia" last="Cui">Hongxia Cui</name><affiliation><nlm:affiliation>Department of Clinical Pharmacology, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China.</nlm:affiliation></affiliation></author><author><name sortKey="Zheng, Lihong" sort="Zheng, Lihong" uniqKey="Zheng L" first="Lihong" last="Zheng">Lihong Zheng</name><affiliation><nlm:affiliation>Department of Biology Genetics, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China.</nlm:affiliation></affiliation></author><author><name sortKey="Zhang, Chunjing" sort="Zhang, Chunjing" uniqKey="Zhang C" first="Chunjing" last="Zhang">Chunjing Zhang</name><affiliation><nlm:affiliation>Department of Biochemistry, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China.</nlm:affiliation></affiliation></author><author><name sortKey="Yue, Liling" sort="Yue, Liling" uniqKey="Yue L" first="Liling" last="Yue">Liling Yue</name><affiliation><nlm:affiliation>Research Institute of Medicine and Pharmacy, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2018">2018</date><idno type="RBID">pubmed:29658606</idno><idno type="pmid">29658606</idno><idno type="doi">10.3892/or.2018.6363</idno><idno type="wicri:Area/PubMed/Corpus">000115</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000115</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Chloroquine inhibits cell growth in human A549 lung cancer cells by blocking autophagy and inducing mitochondrial‑mediated apoptosis.</title><author><name sortKey="Liu, Likun" sort="Liu, Likun" uniqKey="Liu L" first="Likun" last="Liu">Likun Liu</name><affiliation><nlm:affiliation>Research Institute of Medicine and Pharmacy, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China.</nlm:affiliation></affiliation></author><author><name sortKey="Han, Cuicui" sort="Han, Cuicui" uniqKey="Han C" first="Cuicui" last="Han">Cuicui Han</name><affiliation><nlm:affiliation>Department of Pharmacology, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China.</nlm:affiliation></affiliation></author><author><name sortKey="Yu, Haitao" sort="Yu, Haitao" uniqKey="Yu H" first="Haitao" last="Yu">Haitao Yu</name><affiliation><nlm:affiliation>Department of Biology Genetics, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China.</nlm:affiliation></affiliation></author><author><name sortKey="Zhu, Wenbin" sort="Zhu, Wenbin" uniqKey="Zhu W" first="Wenbin" last="Zhu">Wenbin Zhu</name><affiliation><nlm:affiliation>Research Institute of Medicine and Pharmacy, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China.</nlm:affiliation></affiliation></author><author><name sortKey="Cui, Hongxia" sort="Cui, Hongxia" uniqKey="Cui H" first="Hongxia" last="Cui">Hongxia Cui</name><affiliation><nlm:affiliation>Department of Clinical Pharmacology, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China.</nlm:affiliation></affiliation></author><author><name sortKey="Zheng, Lihong" sort="Zheng, Lihong" uniqKey="Zheng L" first="Lihong" last="Zheng">Lihong Zheng</name><affiliation><nlm:affiliation>Department of Biology Genetics, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China.</nlm:affiliation></affiliation></author><author><name sortKey="Zhang, Chunjing" sort="Zhang, Chunjing" uniqKey="Zhang C" first="Chunjing" last="Zhang">Chunjing Zhang</name><affiliation><nlm:affiliation>Department of Biochemistry, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China.</nlm:affiliation></affiliation></author><author><name sortKey="Yue, Liling" sort="Yue, Liling" uniqKey="Yue L" first="Liling" last="Yue">Liling Yue</name><affiliation><nlm:affiliation>Research Institute of Medicine and Pharmacy, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Oncology reports</title><idno type="eISSN">1791-2431</idno><imprint><date when="2018" type="published">2018</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>A549 Cells</term><term>Autophagy (drug effects)</term><term>Cell Proliferation (drug effects)</term><term>Cell Survival (drug effects)</term><term>Chloroquine (pharmacology)</term><term>Dose-Response Relationship, Drug</term><term>Humans</term><term>Lung Neoplasms (drug therapy)</term><term>Lung Neoplasms (metabolism)</term><term>Membrane Potential, Mitochondrial (drug effects)</term><term>Mitochondria (drug effects)</term><term>Mitochondria (metabolism)</term><term>Phosphatidylinositol 3-Kinases (metabolism)</term><term>Proto-Oncogene Proteins c-akt (metabolism)</term><term>Signal Transduction (drug effects)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Phosphatidylinositol 3-Kinases</term><term>Proto-Oncogene Proteins c-akt</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Chloroquine</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Autophagy</term><term>Cell Proliferation</term><term>Cell Survival</term><term>Membrane Potential, Mitochondrial</term><term>Mitochondria</term><term>Signal Transduction</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Lung Neoplasms</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Lung Neoplasms</term><term>Mitochondria</term></keywords><keywords scheme="MESH" xml:lang="en"><term>A549 Cells</term><term>Dose-Response Relationship, Drug</term><term>Humans</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Chloroquine (CQ) has been revealed to exhibit antitumor activity in several human tumors including lung cancer as mono‑ or add‑on therapy. The antitumor effect of CQ appears to depend on the tumor type, stage and genetic context. Few studies have focused on the mechanism concerning the antitumor effect of CQ monotherapy and the cause and effect relationship among autophagy, apoptosis and CQ in human lung A549 cells. Therefore, the present study aimed to identify the antitumor effect of CQ monotherapy and analyze the possible mechanism. In the present study, we demonstrated that CQ suppressed human A549 cell growth in a dose‑ and time‑dependent manner. CQ‑mediated growth inhibition in A549 cells was characterized by the targeting of the PI3K/AKT pathway, thus, inducing mitochondria‑mediated apoptosis at relatively higher concentrations by downregulating Bcl‑2 expression, increasing the expression level of Bax, decreasing mitochondrial membrane potential, releasing cytochrome c from the mitochondria into the cytosol, activating caspase‑3 and cleaving PARP. Collectively, these findings may offer a new rationale for using CQ as a lung cancer therapy drug in clinical practice.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">29658606</PMID><DateCompleted><Year>2018</Year><Month>09</Month><Day>21</Day></DateCompleted><DateRevised><Year>2018</Year><Month>09</Month><Day>21</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1791-2431</ISSN><JournalIssue CitedMedium="Internet"><Volume>39</Volume><Issue>6</Issue><PubDate><Year>2018</Year><Month>Jun</Month></PubDate></JournalIssue><Title>Oncology reports</Title><ISOAbbreviation>Oncol. Rep.</ISOAbbreviation></Journal><ArticleTitle>Chloroquine inhibits cell growth in human A549 lung cancer cells by blocking autophagy and inducing mitochondrial‑mediated apoptosis.</ArticleTitle><Pagination><MedlinePgn>2807-2816</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.3892/or.2018.6363</ELocationID><Abstract><AbstractText>Chloroquine (CQ) has been revealed to exhibit antitumor activity in several human tumors including lung cancer as mono‑ or add‑on therapy. The antitumor effect of CQ appears to depend on the tumor type, stage and genetic context. Few studies have focused on the mechanism concerning the antitumor effect of CQ monotherapy and the cause and effect relationship among autophagy, apoptosis and CQ in human lung A549 cells. Therefore, the present study aimed to identify the antitumor effect of CQ monotherapy and analyze the possible mechanism. In the present study, we demonstrated that CQ suppressed human A549 cell growth in a dose‑ and time‑dependent manner. CQ‑mediated growth inhibition in A549 cells was characterized by the targeting of the PI3K/AKT pathway, thus, inducing mitochondria‑mediated apoptosis at relatively higher concentrations by downregulating Bcl‑2 expression, increasing the expression level of Bax, decreasing mitochondrial membrane potential, releasing cytochrome c from the mitochondria into the cytosol, activating caspase‑3 and cleaving PARP. Collectively, these findings may offer a new rationale for using CQ as a lung cancer therapy drug in clinical practice.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Liu</LastName><ForeName>Likun</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Research Institute of Medicine and Pharmacy, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Han</LastName><ForeName>Cuicui</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Department of Pharmacology, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yu</LastName><ForeName>Haitao</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Department of Biology Genetics, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhu</LastName><ForeName>Wenbin</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>Research Institute of Medicine and Pharmacy, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cui</LastName><ForeName>Hongxia</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Department of Clinical Pharmacology, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zheng</LastName><ForeName>Lihong</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Department of Biology Genetics, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Chunjing</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Department of Biochemistry, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yue</LastName><ForeName>Liling</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Research Institute of Medicine and Pharmacy, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2018</Year><Month>04</Month><Day>12</Day></ArticleDate></Article><MedlineJournalInfo><Country>Greece</Country><MedlineTA>Oncol Rep</MedlineTA><NlmUniqueID>9422756</NlmUniqueID><ISSNLinking>1021-335X</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>886U3H6UFF</RegistryNumber><NameOfSubstance UI="D002738">Chloroquine</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.1.-</RegistryNumber><NameOfSubstance UI="D019869">Phosphatidylinositol 3-Kinases</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.11.1</RegistryNumber><NameOfSubstance UI="D051057">Proto-Oncogene Proteins c-akt</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000072283" MajorTopicYN="N">A549 Cells</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001343" MajorTopicYN="N">Autophagy</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D049109" MajorTopicYN="N">Cell Proliferation</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002470" MajorTopicYN="N">Cell Survival</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002738" MajorTopicYN="N">Chloroquine</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></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="N">drug therapy</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D053078" MajorTopicYN="N">Membrane Potential, Mitochondrial</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008928" MajorTopicYN="N">Mitochondria</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D019869" MajorTopicYN="N">Phosphatidylinositol 3-Kinases</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D051057" MajorTopicYN="N">Proto-Oncogene Proteins c-akt</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D015398" MajorTopicYN="N">Signal Transduction</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2017</Year><Month>02</Month><Day>04</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2018</Year><Month>03</Month><Day>28</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2018</Year><Month>4</Month><Day>17</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2018</Year><Month>9</Month><Day>22</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2018</Year><Month>4</Month><Day>17</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">29658606</ArticleId><ArticleId IdType="doi">10.3892/or.2018.6363</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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