Anti-cancer effects of CQBTO, a chloroquine, and benzo(e)triazine oxide conjugate.
Identifieur interne : 000071 ( PubMed/Checkpoint ); précédent : 000070; suivant : 000072Anti-cancer effects of CQBTO, a chloroquine, and benzo(e)triazine oxide conjugate.
Auteurs : Ziyang Guo [République populaire de Chine] ; Hailong Pei [République populaire de Chine] ; Jing Nie [République populaire de Chine] ; Wentao Hu [République populaire de Chine] ; Jian Zhang [République populaire de Chine] ; Jiahan Ding [République populaire de Chine] ; Shuxian Pan [République populaire de Chine] ; Bingyan Li [République populaire de Chine] ; Tom K. Hei [États-Unis] ; Weiqiang Chen [République populaire de Chine] ; Guangming Zhou [République populaire de Chine]Source :
- Chemical biology & drug design [ 1747-0285 ] ; 2019.
Descripteurs français
- KwdFr :
- Animaux, Antinéoplasiques (), Antinéoplasiques (pharmacologie), Antinéoplasiques (usage thérapeutique), Chloroquine (), Humains, Lignée cellulaire tumorale, Modèles animaux de maladie humaine, Points de contrôle de la phase G1 du cycle cellulaire (), Souris, Survie cellulaire (), Triazines (), Tumeurs du poumon (traitement médicamenteux).
- MESH :
- pharmacologie : Antinéoplasiques.
- traitement médicamenteux : Tumeurs du poumon.
- usage thérapeutique : Antinéoplasiques.
- Animaux, Antinéoplasiques, Chloroquine, Humains, Lignée cellulaire tumorale, Modèles animaux de maladie humaine, Points de contrôle de la phase G1 du cycle cellulaire, Souris, Survie cellulaire, Triazines.
English descriptors
- KwdEn :
- Animals, Antineoplastic Agents (chemistry), Antineoplastic Agents (pharmacology), Antineoplastic Agents (therapeutic use), Cell Line, Tumor, Cell Survival (drug effects), Chloroquine (chemistry), Disease Models, Animal, G1 Phase Cell Cycle Checkpoints (drug effects), Humans, Lung Neoplasms (drug therapy), Mice, Triazines (chemistry).
- MESH :
- chemical , chemistry : Antineoplastic Agents, Chloroquine, Triazines.
- chemical , pharmacology : Antineoplastic Agents.
- chemical , therapeutic use : Antineoplastic Agents.
- drug effects : Cell Survival, G1 Phase Cell Cycle Checkpoints.
- drug therapy : Lung Neoplasms.
- Animals, Cell Line, Tumor, Disease Models, Animal, Humans, Mice.
Abstract
Autophagy is a self-protective process, and it confers cancer cells resistance against radio-chemotherapeutics. To induce cancer cell death, a series of compounds of 3-((4-((7-chloroquinolin-4-yl)amino)butyl)amino)-7-substituted benzo[e][1,2,4]triazine 1-oxide or CQBTO containing two critical chemical groups were designed and synthesized. One compound, benzo[e][1,2,4]triazine 1-oxide, yielded free radicals to trigger autophagy, and the other one, chloroquine (CQ), was an inhibitor of autophagy. We hypothesized that the compounds could kill cancer cells effectively by inducing incomplete autophagy.
DOI: 10.1111/cbdd.13477
PubMed: 30637976
Affiliations:
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pubmed:30637976Le document en format XML
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<term>Antineoplastic Agents (chemistry)</term>
<term>Antineoplastic Agents (pharmacology)</term>
<term>Antineoplastic Agents (therapeutic use)</term>
<term>Cell Line, Tumor</term>
<term>Cell Survival (drug effects)</term>
<term>Chloroquine (chemistry)</term>
<term>Disease Models, Animal</term>
<term>G1 Phase Cell Cycle Checkpoints (drug effects)</term>
<term>Humans</term>
<term>Lung Neoplasms (drug therapy)</term>
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<term>Antinéoplasiques ()</term>
<term>Antinéoplasiques (pharmacologie)</term>
<term>Antinéoplasiques (usage thérapeutique)</term>
<term>Chloroquine ()</term>
<term>Humains</term>
<term>Lignée cellulaire tumorale</term>
<term>Modèles animaux de maladie humaine</term>
<term>Points de contrôle de la phase G1 du cycle cellulaire ()</term>
<term>Souris</term>
<term>Survie cellulaire ()</term>
<term>Triazines ()</term>
<term>Tumeurs du poumon (traitement médicamenteux)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Antineoplastic Agents</term>
<term>Chloroquine</term>
<term>Triazines</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antineoplastic Agents</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antineoplastic Agents</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Cell Survival</term>
<term>G1 Phase Cell Cycle Checkpoints</term>
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</keywords>
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<term>Cell Line, Tumor</term>
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<term>Mice</term>
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<term>Antinéoplasiques</term>
<term>Chloroquine</term>
<term>Humains</term>
<term>Lignée cellulaire tumorale</term>
<term>Modèles animaux de maladie humaine</term>
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<front><div type="abstract" xml:lang="en">Autophagy is a self-protective process, and it confers cancer cells resistance against radio-chemotherapeutics. To induce cancer cell death, a series of compounds of 3-((4-((7-chloroquinolin-4-yl)amino)butyl)amino)-7-substituted benzo[e][1,2,4]triazine 1-oxide or CQBTO containing two critical chemical groups were designed and synthesized. One compound, benzo[e][1,2,4]triazine 1-oxide, yielded free radicals to trigger autophagy, and the other one, chloroquine (CQ), was an inhibitor of autophagy. We hypothesized that the compounds could kill cancer cells effectively by inducing incomplete autophagy.</div>
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<Issue>5</Issue>
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<ArticleTitle>Anti-cancer effects of CQBTO, a chloroquine, and benzo(e)triazine oxide conjugate.</ArticleTitle>
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</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1111/cbdd.13477</ELocationID>
<Abstract><AbstractText Label="AIM">Autophagy is a self-protective process, and it confers cancer cells resistance against radio-chemotherapeutics. To induce cancer cell death, a series of compounds of 3-((4-((7-chloroquinolin-4-yl)amino)butyl)amino)-7-substituted benzo[e][1,2,4]triazine 1-oxide or CQBTO containing two critical chemical groups were designed and synthesized. One compound, benzo[e][1,2,4]triazine 1-oxide, yielded free radicals to trigger autophagy, and the other one, chloroquine (CQ), was an inhibitor of autophagy. We hypothesized that the compounds could kill cancer cells effectively by inducing incomplete autophagy.</AbstractText>
<AbstractText Label="METHODS">In vitro cultured non-small cell lung carcinoma cells and primary lung tumors in mice in vivo were used to test the lethal effects of CQBTO on cancer cells and toxicity to normal tissues. Cell viability was examined using the CCK8 assay. Genomic instability was determined with the cytochalasin B-blocked micronucleus assay. Cell cycle distribution was analyzed by propidium iodide staining and flow cytometry. Western blotting and immunofluorescence were used to detect the induction and localization of LC3, a biomarker for autophagy.</AbstractText>
<AbstractText Label="RESULTS">Compared with CQ, three CQBTO compounds were lethal to lung cancer cells, and CQBTO-3 was the most effective. The LD50 for CQBTO-3 was 21 μΜ in A549 cells and 21.5 μΜ in Calu-1 cells, which was lower than that of CQBTO-2 or CQBTO-1. Induction of LC3 foci and an increase in the LC3II/LC3I ratio demonstrated the induction of autophagy by CQBTO-3 in A549 cells, whereas no obvious micronuclei or cell cycle arrest was observed. No detectable toxicity to normal mice was observed. CQBTO-3 improved the quality of mouse life, reduced the number and size of existing tumors, and suppressed tumor formation.</AbstractText>
<AbstractText Label="CONCLUSION">CQBTO-3 is a potential chemical compound for lung cancer treatment.</AbstractText>
<CopyrightInformation>© 2019 John Wiley & Sons A/S.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Guo</LastName>
<ForeName>Ziyang</ForeName>
<Initials>Z</Initials>
<AffiliationInfo><Affiliation>State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Institute of Space Life Sciences, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Medical College of Soochow University, Suzhou, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Pei</LastName>
<ForeName>Hailong</ForeName>
<Initials>H</Initials>
<AffiliationInfo><Affiliation>State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Institute of Space Life Sciences, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Medical College of Soochow University, Suzhou, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Nie</LastName>
<ForeName>Jing</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Institute of Space Life Sciences, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Medical College of Soochow University, Suzhou, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Hu</LastName>
<ForeName>Wentao</ForeName>
<Initials>W</Initials>
<AffiliationInfo><Affiliation>State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Institute of Space Life Sciences, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Medical College of Soochow University, Suzhou, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Zhang</LastName>
<ForeName>Jian</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Institute of Space Life Sciences, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Medical College of Soochow University, Suzhou, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Ding</LastName>
<ForeName>Jiahan</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Institute of Space Life Sciences, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Medical College of Soochow University, Suzhou, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Pan</LastName>
<ForeName>Shuxian</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Institute of Space Life Sciences, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Medical College of Soochow University, Suzhou, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Li</LastName>
<ForeName>Bingyan</ForeName>
<Initials>B</Initials>
<AffiliationInfo><Affiliation>State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Institute of Space Life Sciences, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Medical College of Soochow University, Suzhou, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Hei</LastName>
<ForeName>Tom K</ForeName>
<Initials>TK</Initials>
<AffiliationInfo><Affiliation>Center for Radiological Research, College of Physician and Surgeons, Columbia University, New York, New York.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Chen</LastName>
<ForeName>Weiqiang</ForeName>
<Initials>W</Initials>
<AffiliationInfo><Affiliation>Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Zhou</LastName>
<ForeName>Guangming</ForeName>
<Initials>G</Initials>
<Identifier Source="ORCID">0000-0001-5695-2308</Identifier>
<AffiliationInfo><Affiliation>State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Institute of Space Life Sciences, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Medical College of Soochow University, Suzhou, China.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
<PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic"><Year>2019</Year>
<Month>02</Month>
<Day>12</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>England</Country>
<MedlineTA>Chem Biol Drug Des</MedlineTA>
<NlmUniqueID>101262549</NlmUniqueID>
<ISSNLinking>1747-0277</ISSNLinking>
</MedlineJournalInfo>
<ChemicalList><Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D000970">Antineoplastic Agents</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D014227">Triazines</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>886U3H6UFF</RegistryNumber>
<NameOfSubstance UI="D002738">Chloroquine</NameOfSubstance>
</Chemical>
</ChemicalList>
<CitationSubset>IM</CitationSubset>
<MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000970" MajorTopicYN="N">Antineoplastic Agents</DescriptorName>
<QualifierName UI="Q000737" MajorTopicYN="Y">chemistry</QualifierName>
<QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName>
<QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</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>
</MeshHeading>
<MeshHeading><DescriptorName UI="D002738" MajorTopicYN="N">Chloroquine</DescriptorName>
<QualifierName UI="Q000737" MajorTopicYN="Y">chemistry</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D004195" MajorTopicYN="N">Disease Models, Animal</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D059585" MajorTopicYN="N">G1 Phase Cell Cycle Checkpoints</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
</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>
</MeshHeading>
<MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D014227" MajorTopicYN="N">Triazines</DescriptorName>
<QualifierName UI="Q000737" MajorTopicYN="Y">chemistry</QualifierName>
</MeshHeading>
</MeshHeadingList>
<KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="Y">autophagy</Keyword>
<Keyword MajorTopicYN="Y">cell cycle arrest</Keyword>
<Keyword MajorTopicYN="Y">chloroquine</Keyword>
<Keyword MajorTopicYN="Y">lung cancer</Keyword>
<Keyword MajorTopicYN="Y">primary mouse lung tumor</Keyword>
</KeywordList>
</MedlineCitation>
<PubmedData><History><PubMedPubDate PubStatus="received"><Year>2018</Year>
<Month>08</Month>
<Day>07</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="revised"><Year>2018</Year>
<Month>12</Month>
<Day>11</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="accepted"><Year>2018</Year>
<Month>12</Month>
<Day>16</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="pubmed"><Year>2019</Year>
<Month>1</Month>
<Day>15</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="medline"><Year>2020</Year>
<Month>2</Month>
<Day>28</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="entrez"><Year>2019</Year>
<Month>1</Month>
<Day>15</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
</History>
<PublicationStatus>ppublish</PublicationStatus>
<ArticleIdList><ArticleId IdType="pubmed">30637976</ArticleId>
<ArticleId IdType="doi">10.1111/cbdd.13477</ArticleId>
</ArticleIdList>
</PubmedData>
</pubmed>
<affiliations><list><country><li>République populaire de Chine</li>
<li>États-Unis</li>
</country>
<region><li>État de New York</li>
</region>
</list>
<tree><country name="République populaire de Chine"><noRegion><name sortKey="Guo, Ziyang" sort="Guo, Ziyang" uniqKey="Guo Z" first="Ziyang" last="Guo">Ziyang Guo</name>
</noRegion>
<name sortKey="Chen, Weiqiang" sort="Chen, Weiqiang" uniqKey="Chen W" first="Weiqiang" last="Chen">Weiqiang Chen</name>
<name sortKey="Ding, Jiahan" sort="Ding, Jiahan" uniqKey="Ding J" first="Jiahan" last="Ding">Jiahan Ding</name>
<name sortKey="Hu, Wentao" sort="Hu, Wentao" uniqKey="Hu W" first="Wentao" last="Hu">Wentao Hu</name>
<name sortKey="Li, Bingyan" sort="Li, Bingyan" uniqKey="Li B" first="Bingyan" last="Li">Bingyan Li</name>
<name sortKey="Nie, Jing" sort="Nie, Jing" uniqKey="Nie J" first="Jing" last="Nie">Jing Nie</name>
<name sortKey="Pan, Shuxian" sort="Pan, Shuxian" uniqKey="Pan S" first="Shuxian" last="Pan">Shuxian Pan</name>
<name sortKey="Pei, Hailong" sort="Pei, Hailong" uniqKey="Pei H" first="Hailong" last="Pei">Hailong Pei</name>
<name sortKey="Zhang, Jian" sort="Zhang, Jian" uniqKey="Zhang J" first="Jian" last="Zhang">Jian Zhang</name>
<name sortKey="Zhou, Guangming" sort="Zhou, Guangming" uniqKey="Zhou G" first="Guangming" last="Zhou">Guangming Zhou</name>
</country>
<country name="États-Unis"><region name="État de New York"><name sortKey="Hei, Tom K" sort="Hei, Tom K" uniqKey="Hei T" first="Tom K" last="Hei">Tom K. Hei</name>
</region>
</country>
</tree>
</affiliations>
</record>
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