Chloroquine enhances the cytotoxicity of topotecan by inhibiting autophagy in lung cancer cells.
Identifieur interne : 001475 ( Main/Exploration ); précédent : 001474; suivant : 001476Chloroquine enhances the cytotoxicity of topotecan by inhibiting autophagy in lung cancer cells.
Auteurs : Yao Wang [République populaire de Chine] ; Rui-Qing Peng ; Dan-Dan Li ; Ya Ding ; Xiao-Qi Wu ; Yi-Xin Zeng ; Xiao-Feng Zhu ; Xiao-Shi ZhangSource :
- Chinese journal of cancer [ 1000-467X ] ; 2011.
Descripteurs français
- KwdFr :
- Apoptose (), Autophagie (), Chloroquine (pharmacologie), Humains, Inhibiteurs de la topoisomérase-I (pharmacologie), Lignée cellulaire tumorale, Prolifération cellulaire (), Protéine Bax (métabolisme), Protéine-11 analogue à Bcl-2, Protéines membranaires (métabolisme), Protéines proto-oncogènes (métabolisme), Protéines proto-oncogènes c-bcl-2 (métabolisme), Protéines régulatrices de l'apoptose (métabolisme), Synergie des médicaments, Topotécane (pharmacologie), Tumeurs du poumon (anatomopathologie), Tumeurs du poumon (métabolisme).
- MESH :
- anatomopathologie : Tumeurs du poumon.
- métabolisme : Protéine Bax, Protéines membranaires, Protéines proto-oncogènes, Protéines proto-oncogènes c-bcl-2, Protéines régulatrices de l'apoptose, Tumeurs du poumon.
- pharmacologie : Chloroquine, Inhibiteurs de la topoisomérase-I, Topotécane.
- Apoptose, Autophagie, Humains, Lignée cellulaire tumorale, Prolifération cellulaire, Protéine-11 analogue à Bcl-2, Synergie des médicaments.
English descriptors
- KwdEn :
- Apoptosis (drug effects), Apoptosis Regulatory Proteins (metabolism), Autophagy (drug effects), Bcl-2-Like Protein 11, Cell Line, Tumor, Cell Proliferation (drug effects), Chloroquine (pharmacology), Drug Synergism, Humans, Lung Neoplasms (metabolism), Lung Neoplasms (pathology), Membrane Proteins (metabolism), Proto-Oncogene Proteins (metabolism), Proto-Oncogene Proteins c-bcl-2 (metabolism), Topoisomerase I Inhibitors (pharmacology), Topotecan (pharmacology), bcl-2-Associated X Protein (metabolism).
- MESH :
- chemical , metabolism : Apoptosis Regulatory Proteins, Membrane Proteins, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-bcl-2, bcl-2-Associated X Protein.
- drug effects : Apoptosis, Autophagy, Cell Proliferation.
- metabolism : Lung Neoplasms.
- pathology : Lung Neoplasms.
- chemical , pharmacology : Chloroquine, Topoisomerase I Inhibitors, Topotecan.
- chemical : Bcl-2-Like Protein 11, Cell Line, Tumor, Drug Synergism, Humans.
Abstract
Although the anti-malaria drug chloroquine (CQ) has been shown to enhance chemotherapy and radiation sensitivity in clinical trials, the potential mechanisms underlying this enhancement are still unclear. Here, we examined the relevant mechanisms by which the multipotent CQ enhanced the cytotoxicity of topotecan (TPT). The lung cancer cell line A549 was treated with TPT alone or TPT combined with CQ at non-cytotoxic concentrations. Cell viability was assessed using the MTT assay. The percentage of apoptotic cells and the presence of a side population of cells were both determined by flow cytometry. Autophagy and the expression of Bcl-2 family proteins were examined by Western blotting. The accumulation of YFP-LC3 dots and the formation of acidic vesicular organelles were examined by confocal microscopy. CQ sensitized A549 cells to TPT and enhanced TPT-induced apoptosis in a Bcl-2 family protein-independent fashion. CQ inhibited TPT-induced autophagy, which modified the cytotoxicity of TPT. However, CQ failed to modify the transfer of TPT across the cytoplasmic membrane and did not increase lysosomal permeability. This study showed that CQ at non-cytotoxic concentrations potentiated the cytotoxicity of TPT by interfering with autophagy, implying that CQ has significant potential as a chemotherapeutic enhancer.
DOI: 10.5732/cjc.011.10056
PubMed: 21959046
Affiliations:
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Le document en format XML
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Zhu</name></author><author><name sortKey="Zhang, Xiao Shi" sort="Zhang, Xiao Shi" uniqKey="Zhang X" first="Xiao-Shi" last="Zhang">Xiao-Shi Zhang</name></author></analytic><series><title level="j">Chinese journal of cancer</title><idno type="ISSN">1000-467X</idno><imprint><date when="2011" type="published">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Apoptosis (drug effects)</term><term>Apoptosis Regulatory Proteins (metabolism)</term><term>Autophagy (drug effects)</term><term>Bcl-2-Like Protein 11</term><term>Cell Line, Tumor</term><term>Cell Proliferation (drug effects)</term><term>Chloroquine (pharmacology)</term><term>Drug Synergism</term><term>Humans</term><term>Lung Neoplasms (metabolism)</term><term>Lung Neoplasms (pathology)</term><term>Membrane Proteins (metabolism)</term><term>Proto-Oncogene Proteins (metabolism)</term><term>Proto-Oncogene Proteins c-bcl-2 (metabolism)</term><term>Topoisomerase I Inhibitors (pharmacology)</term><term>Topotecan (pharmacology)</term><term>bcl-2-Associated X Protein (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Apoptose ()</term><term>Autophagie ()</term><term>Chloroquine (pharmacologie)</term><term>Humains</term><term>Inhibiteurs de la topoisomérase-I (pharmacologie)</term><term>Lignée cellulaire tumorale</term><term>Prolifération cellulaire ()</term><term>Protéine Bax (métabolisme)</term><term>Protéine-11 analogue à Bcl-2</term><term>Protéines membranaires (métabolisme)</term><term>Protéines proto-oncogènes (métabolisme)</term><term>Protéines proto-oncogènes c-bcl-2 (métabolisme)</term><term>Protéines régulatrices de l'apoptose (métabolisme)</term><term>Synergie des médicaments</term><term>Topotécane (pharmacologie)</term><term>Tumeurs du poumon (anatomopathologie)</term><term>Tumeurs du poumon (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Apoptosis Regulatory Proteins</term><term>Membrane Proteins</term><term>Proto-Oncogene Proteins</term><term>Proto-Oncogene Proteins c-bcl-2</term><term>bcl-2-Associated X Protein</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><term>Autophagy</term><term>Cell Proliferation</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Lung Neoplasms</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Protéine Bax</term><term>Protéines membranaires</term><term>Protéines proto-oncogènes</term><term>Protéines proto-oncogènes c-bcl-2</term><term>Protéines régulatrices de l'apoptose</term><term>Tumeurs du poumon</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Lung Neoplasms</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Chloroquine</term><term>Inhibiteurs de la topoisomérase-I</term><term>Topotécane</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Chloroquine</term><term>Topoisomerase I Inhibitors</term><term>Topotecan</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>Bcl-2-Like Protein 11</term><term>Cell Line, Tumor</term><term>Drug Synergism</term><term>Humans</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Apoptose</term><term>Autophagie</term><term>Humains</term><term>Lignée cellulaire tumorale</term><term>Prolifération cellulaire</term><term>Protéine-11 analogue à Bcl-2</term><term>Synergie des médicaments</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Although the anti-malaria drug chloroquine (CQ) has been shown to enhance chemotherapy and radiation sensitivity in clinical trials, the potential mechanisms underlying this enhancement are still unclear. Here, we examined the relevant mechanisms by which the multipotent CQ enhanced the cytotoxicity of topotecan (TPT). The lung cancer cell line A549 was treated with TPT alone or TPT combined with CQ at non-cytotoxic concentrations. Cell viability was assessed using the MTT assay. The percentage of apoptotic cells and the presence of a side population of cells were both determined by flow cytometry. Autophagy and the expression of Bcl-2 family proteins were examined by Western blotting. The accumulation of YFP-LC3 dots and the formation of acidic vesicular organelles were examined by confocal microscopy. CQ sensitized A549 cells to TPT and enhanced TPT-induced apoptosis in a Bcl-2 family protein-independent fashion. CQ inhibited TPT-induced autophagy, which modified the cytotoxicity of TPT. However, CQ failed to modify the transfer of TPT across the cytoplasmic membrane and did not increase lysosomal permeability. This study showed that CQ at non-cytotoxic concentrations potentiated the cytotoxicity of TPT by interfering with autophagy, implying that CQ has significant potential as a chemotherapeutic enhancer.</div></front></TEI><affiliations><list><country><li>République populaire de Chine</li></country></list><tree><noCountry><name sortKey="Ding, Ya" sort="Ding, Ya" uniqKey="Ding Y" first="Ya" last="Ding">Ya Ding</name><name sortKey="Li, Dan Dan" sort="Li, Dan Dan" uniqKey="Li D" first="Dan-Dan" last="Li">Dan-Dan Li</name><name sortKey="Peng, Rui Qing" sort="Peng, Rui Qing" uniqKey="Peng R" first="Rui-Qing" last="Peng">Rui-Qing Peng</name><name sortKey="Wu, Xiao Qi" sort="Wu, Xiao Qi" uniqKey="Wu X" first="Xiao-Qi" last="Wu">Xiao-Qi Wu</name><name sortKey="Zeng, Yi Xin" sort="Zeng, Yi Xin" uniqKey="Zeng Y" first="Yi-Xin" last="Zeng">Yi-Xin Zeng</name><name sortKey="Zhang, Xiao Shi" sort="Zhang, Xiao Shi" uniqKey="Zhang X" first="Xiao-Shi" last="Zhang">Xiao-Shi Zhang</name><name sortKey="Zhu, Xiao Feng" sort="Zhu, Xiao Feng" uniqKey="Zhu X" first="Xiao-Feng" last="Zhu">Xiao-Feng Zhu</name></noCountry><country name="République populaire de Chine"><noRegion><name sortKey="Wang, Yao" sort="Wang, Yao" uniqKey="Wang Y" first="Yao" last="Wang">Yao Wang</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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