[Chloroquine inhibits viability of renal carcinoma cells and enhances sunitinib-induced caspase-dependent apoptosis].
Identifieur interne : 000428 ( Main/Corpus ); précédent : 000427; suivant : 000429[Chloroquine inhibits viability of renal carcinoma cells and enhances sunitinib-induced caspase-dependent apoptosis].
Auteurs : J. Sun ; W D Song ; S Y Yan ; Z J XiSource :
- Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences [ 1671-167X ] ; 2018.
English descriptors
- KwdEn :
- MESH :
- chemical , pharmacology : Antineoplastic Agents, Antirheumatic Agents, Chloroquine, Sunitinib.
- drug effects : Apoptosis, Autophagy.
- drug therapy : Kidney Neoplasms.
- Animals, Caspases, Cell Line, Tumor.
Abstract
OBJECTIVE
To determine whether chloroquine (CQ), an often used inhibitor of late autophagy and autophagosome/lyosome fusion, can inhibit proliferation of renal carcinoma cells and investigate its effect on sunitinib (ST)-induced apoptosis.
METHODS
Renal carcinoma cell line 786 O and ACHN had been used as cellular model and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay was carried out to detect the cell viability in response to CQ or ST treatment. Both transmission electron microscope and immunoblotting had been employed to observe apoptotic and autophagic process. To examine the involvement of autophagy in ST-dependent apoptosis, autophagy had been inhibited either chemically or genetically via utilizing autophagy inhibitor or specific small interference RNA (siRNA) targeted to either Ulk1 (unc-51-like kinase 1) or LC3 (microtubule associated protein 1 light chain 3 fusion protein), two essential autophagic proteins.
RESULTS
Both ST and CQ induced cell viability loss, indicating that either of them could inhibit renal cancer cell proliferation. Clone formation experiments confirmed the aforementioned results. Furthermore, the combined ST with CQ synergistically promoted the loss of cell viability. By transmission electron microscopy and immunoblotting, we found that the ST induced both autophagy and caspase-dependent apoptosis. While 3-MA, an early autophagy inhibitor, reduced the ST-induced cleavage of poly (ADP-ribose) polymerase-1 (PARP-1), a substrate of caspase 3/7 and often used marker of caspase-dependent apoptosis, CQ promoted the ST-dependent PARP-1 cleavage, indicating that the early and late autophagy functioned differentially on the ST-activated apoptotic process. Moreover, the knock down of either Ulk1 or LC3 decreased the ST-caused apoptosis.Interestingly, we observed that rapamycin, a specific inhibitor of mTOR (mammalian target of rapamycin) and an inducer of autophagy, also showed to inhibit cell viability and increased the cleavage of PARP-1 in the ST-treated cells, suggesting that autophagy was likely to play a dual role in the regulation of the ST-induced apoptosis.
CONCLUSION
ST activates both apoptotic and autophagic process in renal carcinoma cells. Although autophagy precedes the ST-induced apoptosis, however, early and late autophagy functions differentially on the apoptotic process induced by this compound. Additionally, ST can coordinate with the inducer of autophagy to inhibit the cell proliferation. Further research in this direction will let us illuminate to utilize CQ as a potential drug in the treatment of renal carcinoma.
PubMed: 30337735
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pubmed:30337735Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">[Chloroquine inhibits viability of renal carcinoma cells and enhances sunitinib-induced caspase-dependent apoptosis].</title><author><name sortKey="Sun, J" sort="Sun, J" uniqKey="Sun J" first="J" last="Sun">J. Sun</name><affiliation><nlm:affiliation>Department of Pathology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China; Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.</nlm:affiliation></affiliation></author><author><name sortKey="Song, W D" sort="Song, W D" uniqKey="Song W" first="W D" last="Song">W D Song</name><affiliation><nlm:affiliation>Department of Urology, Peking University First Hospital,Institute of Urology,Peking University,Beijing 100034, China.</nlm:affiliation></affiliation></author><author><name sortKey="Yan, S Y" sort="Yan, S Y" uniqKey="Yan S" first="S Y" last="Yan">S Y Yan</name><affiliation><nlm:affiliation>Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.</nlm:affiliation></affiliation></author><author><name sortKey="Xi, Z J" sort="Xi, Z J" uniqKey="Xi Z" first="Z J" last="Xi">Z J Xi</name><affiliation><nlm:affiliation>Department of Urology, Peking University First Hospital,Institute of Urology,Peking University,Beijing 100034, China.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2018">2018</date><idno type="RBID">pubmed:30337735</idno><idno type="pmid">30337735</idno><idno type="wicri:Area/Main/Corpus">000428</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000428</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">[Chloroquine inhibits viability of renal carcinoma cells and enhances sunitinib-induced caspase-dependent apoptosis].</title><author><name sortKey="Sun, J" sort="Sun, J" uniqKey="Sun J" first="J" last="Sun">J. Sun</name><affiliation><nlm:affiliation>Department of Pathology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China; Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.</nlm:affiliation></affiliation></author><author><name sortKey="Song, W D" sort="Song, W D" uniqKey="Song W" first="W D" last="Song">W D Song</name><affiliation><nlm:affiliation>Department of Urology, Peking University First Hospital,Institute of Urology,Peking University,Beijing 100034, China.</nlm:affiliation></affiliation></author><author><name sortKey="Yan, S Y" sort="Yan, S Y" uniqKey="Yan S" first="S Y" last="Yan">S Y Yan</name><affiliation><nlm:affiliation>Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.</nlm:affiliation></affiliation></author><author><name sortKey="Xi, Z J" sort="Xi, Z J" uniqKey="Xi Z" first="Z J" last="Xi">Z J Xi</name><affiliation><nlm:affiliation>Department of Urology, Peking University First Hospital,Institute of Urology,Peking University,Beijing 100034, China.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences</title><idno type="ISSN">1671-167X</idno><imprint><date when="2018" type="published">2018</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals (MeSH)</term><term>Antineoplastic Agents (pharmacology)</term><term>Antirheumatic Agents (pharmacology)</term><term>Apoptosis (drug effects)</term><term>Autophagy (drug effects)</term><term>Caspases (MeSH)</term><term>Cell Line, Tumor (MeSH)</term><term>Chloroquine (pharmacology)</term><term>Kidney Neoplasms (drug therapy)</term><term>Sunitinib (pharmacology)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antineoplastic Agents</term><term>Antirheumatic Agents</term><term>Chloroquine</term><term>Sunitinib</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Apoptosis</term><term>Autophagy</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Kidney Neoplasms</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Caspases</term><term>Cell Line, Tumor</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><b>OBJECTIVE</b></p><p>To determine whether chloroquine (CQ), an often used inhibitor of late autophagy and autophagosome/lyosome fusion, can inhibit proliferation of renal carcinoma cells and investigate its effect on sunitinib (ST)-induced apoptosis.</p></div><div type="abstract" xml:lang="en"><p><b>METHODS</b></p><p>Renal carcinoma cell line 786 O and ACHN had been used as cellular model and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay was carried out to detect the cell viability in response to CQ or ST treatment. Both transmission electron microscope and immunoblotting had been employed to observe apoptotic and autophagic process. To examine the involvement of autophagy in ST-dependent apoptosis, autophagy had been inhibited either chemically or genetically via utilizing autophagy inhibitor or specific small interference RNA (siRNA) targeted to either Ulk1 (unc-51-like kinase 1) or LC3 (microtubule associated protein 1 light chain 3 fusion protein), two essential autophagic proteins.</p></div><div type="abstract" xml:lang="en"><p><b>RESULTS</b></p><p>Both ST and CQ induced cell viability loss, indicating that either of them could inhibit renal cancer cell proliferation. Clone formation experiments confirmed the aforementioned results. Furthermore, the combined ST with CQ synergistically promoted the loss of cell viability. By transmission electron microscopy and immunoblotting, we found that the ST induced both autophagy and caspase-dependent apoptosis. While 3-MA, an early autophagy inhibitor, reduced the ST-induced cleavage of poly (ADP-ribose) polymerase-1 (PARP-1), a substrate of caspase 3/7 and often used marker of caspase-dependent apoptosis, CQ promoted the ST-dependent PARP-1 cleavage, indicating that the early and late autophagy functioned differentially on the ST-activated apoptotic process. Moreover, the knock down of either Ulk1 or LC3 decreased the ST-caused apoptosis.Interestingly, we observed that rapamycin, a specific inhibitor of mTOR (mammalian target of rapamycin) and an inducer of autophagy, also showed to inhibit cell viability and increased the cleavage of PARP-1 in the ST-treated cells, suggesting that autophagy was likely to play a dual role in the regulation of the ST-induced apoptosis.</p></div><div type="abstract" xml:lang="en"><p><b>CONCLUSION</b></p><p>ST activates both apoptotic and autophagic process in renal carcinoma cells. Although autophagy precedes the ST-induced apoptosis, however, early and late autophagy functions differentially on the apoptotic process induced by this compound. Additionally, ST can coordinate with the inducer of autophagy to inhibit the cell proliferation. Further research in this direction will let us illuminate to utilize CQ as a potential drug in the treatment of renal carcinoma.</p></div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" IndexingMethod="Curated" Owner="NLM"><PMID Version="1">30337735</PMID><DateCompleted><Year>2019</Year><Month>03</Month><Day>05</Day></DateCompleted><DateRevised><Year>2019</Year><Month>03</Month><Day>05</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">1671-167X</ISSN><JournalIssue CitedMedium="Print"><Volume>50</Volume><Issue>5</Issue><PubDate><Year>2018</Year><Month>Oct</Month><Day>18</Day></PubDate></JournalIssue><Title>Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences</Title><ISOAbbreviation>Beijing Da Xue Xue Bao Yi Xue Ban</ISOAbbreviation></Journal><ArticleTitle>[Chloroquine inhibits viability of renal carcinoma cells and enhances sunitinib-induced caspase-dependent apoptosis].</ArticleTitle><Pagination><MedlinePgn>778-784</MedlinePgn></Pagination><Abstract><AbstractText Label="OBJECTIVE" NlmCategory="OBJECTIVE">To determine whether chloroquine (CQ), an often used inhibitor of late autophagy and autophagosome/lyosome fusion, can inhibit proliferation of renal carcinoma cells and investigate its effect on sunitinib (ST)-induced apoptosis.</AbstractText><AbstractText Label="METHODS" NlmCategory="METHODS">Renal carcinoma cell line 786 O and ACHN had been used as cellular model and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay was carried out to detect the cell viability in response to CQ or ST treatment. Both transmission electron microscope and immunoblotting had been employed to observe apoptotic and autophagic process. To examine the involvement of autophagy in ST-dependent apoptosis, autophagy had been inhibited either chemically or genetically via utilizing autophagy inhibitor or specific small interference RNA (siRNA) targeted to either Ulk1 (unc-51-like kinase 1) or LC3 (microtubule associated protein 1 light chain 3 fusion protein), two essential autophagic proteins.</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">Both ST and CQ induced cell viability loss, indicating that either of them could inhibit renal cancer cell proliferation. Clone formation experiments confirmed the aforementioned results. Furthermore, the combined ST with CQ synergistically promoted the loss of cell viability. By transmission electron microscopy and immunoblotting, we found that the ST induced both autophagy and caspase-dependent apoptosis. While 3-MA, an early autophagy inhibitor, reduced the ST-induced cleavage of poly (ADP-ribose) polymerase-1 (PARP-1), a substrate of caspase 3/7 and often used marker of caspase-dependent apoptosis, CQ promoted the ST-dependent PARP-1 cleavage, indicating that the early and late autophagy functioned differentially on the ST-activated apoptotic process. Moreover, the knock down of either Ulk1 or LC3 decreased the ST-caused apoptosis.Interestingly, we observed that rapamycin, a specific inhibitor of mTOR (mammalian target of rapamycin) and an inducer of autophagy, also showed to inhibit cell viability and increased the cleavage of PARP-1 in the ST-treated cells, suggesting that autophagy was likely to play a dual role in the regulation of the ST-induced apoptosis.</AbstractText><AbstractText Label="CONCLUSION" NlmCategory="CONCLUSIONS">ST activates both apoptotic and autophagic process in renal carcinoma cells. Although autophagy precedes the ST-induced apoptosis, however, early and late autophagy functions differentially on the apoptotic process induced by this compound. Additionally, ST can coordinate with the inducer of autophagy to inhibit the cell proliferation. Further research in this direction will let us illuminate to utilize CQ as a potential drug in the treatment of renal carcinoma.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Sun</LastName><ForeName>J</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Pathology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China; Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Song</LastName><ForeName>W D</ForeName><Initials>WD</Initials><AffiliationInfo><Affiliation>Department of Urology, Peking University First Hospital,Institute of Urology,Peking University,Beijing 100034, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yan</LastName><ForeName>S Y</ForeName><Initials>SY</Initials><AffiliationInfo><Affiliation>Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Xi</LastName><ForeName>Z J</ForeName><Initials>ZJ</Initials><AffiliationInfo><Affiliation>Department of Urology, Peking University First Hospital,Institute of Urology,Peking University,Beijing 100034, China.</Affiliation></AffiliationInfo></Author></AuthorList><Language>chi</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>China</Country><MedlineTA>Beijing Da Xue Xue Bao Yi Xue Ban</MedlineTA><NlmUniqueID>101125284</NlmUniqueID><ISSNLinking>1671-167X</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000970">Antineoplastic Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D018501">Antirheumatic Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>886U3H6UFF</RegistryNumber><NameOfSubstance UI="D002738">Chloroquine</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 3.4.22.-</RegistryNumber><NameOfSubstance UI="D020169">Caspases</NameOfSubstance></Chemical><Chemical><RegistryNumber>V99T50803M</RegistryNumber><NameOfSubstance UI="D000077210">Sunitinib</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000970" MajorTopicYN="Y">Antineoplastic Agents</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018501" MajorTopicYN="Y">Antirheumatic Agents</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D017209" MajorTopicYN="Y">Apoptosis</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001343" MajorTopicYN="N">Autophagy</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D020169" MajorTopicYN="N">Caspases</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D045744" MajorTopicYN="N">Cell Line, Tumor</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002738" MajorTopicYN="Y">Chloroquine</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007680" MajorTopicYN="Y">Kidney Neoplasms</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="N">drug therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000077210" MajorTopicYN="Y">Sunitinib</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2018</Year><Month>10</Month><Day>20</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2018</Year><Month>10</Month><Day>20</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2019</Year><Month>3</Month><Day>6</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">30337735</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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