Honokiol exhibits enhanced antitumor effects with chloroquine by inducing cell death and inhibiting autophagy in human non-small cell lung cancer cells.
Identifieur interne : 000E86 ( Main/Exploration ); précédent : 000E85; suivant : 000E87Honokiol exhibits enhanced antitumor effects with chloroquine by inducing cell death and inhibiting autophagy in human non-small cell lung cancer cells.
Auteurs : Xiaoqin Lv [République populaire de Chine] ; Fang Liu [République populaire de Chine] ; Yue Shang [République populaire de Chine] ; Shu-Zhen Chen [République populaire de Chine]Source :
- Oncology reports [ 1791-2431 ] ; 2015.
Descripteurs français
- KwdFr :
- Animaux, Apoptose (), Autophagie (), Carcinome pulmonaire non à petites cellules (anatomopathologie), Carcinome pulmonaire non à petites cellules (traitement médicamenteux), Chloroquine (administration et posologie), Dérivés du biphényle (administration et posologie), Humains, Lignanes (administration et posologie), Lignée cellulaire tumorale, Prolifération cellulaire (), Protéines tumorales (), Régulation de l'expression des gènes tumoraux (), Souris, Synergie des médicaments, Tests d'activité antitumorale sur modèle de xénogreffe.
- MESH :
- administration et posologie : Chloroquine, Dérivés du biphényle, Lignanes.
- anatomopathologie : Carcinome pulmonaire non à petites cellules.
- traitement médicamenteux : Carcinome pulmonaire non à petites cellules.
- Animaux, Apoptose, Autophagie, Humains, Lignée cellulaire tumorale, Prolifération cellulaire, Protéines tumorales, Régulation de l'expression des gènes tumoraux, Souris, Synergie des médicaments, Tests d'activité antitumorale sur modèle de xénogreffe.
English descriptors
- KwdEn :
- Animals, Apoptosis (drug effects), Autophagy (drug effects), Biphenyl Compounds (administration & dosage), Carcinoma, Non-Small-Cell Lung (drug therapy), Carcinoma, Non-Small-Cell Lung (pathology), Cell Line, Tumor, Cell Proliferation (drug effects), Chloroquine (administration & dosage), Drug Synergism, Gene Expression Regulation, Neoplastic (drug effects), Humans, Lignans (administration & dosage), Mice, Neoplasm Proteins (drug effects), Xenograft Model Antitumor Assays.
- MESH :
- chemical , administration & dosage : Biphenyl Compounds, Chloroquine, Lignans.
- drug effects : Apoptosis, Autophagy, Cell Proliferation, Gene Expression Regulation, Neoplastic, Neoplasm Proteins.
- drug therapy : Carcinoma, Non-Small-Cell Lung.
- pathology : Carcinoma, Non-Small-Cell Lung.
- Animals, Cell Line, Tumor, Drug Synergism, Humans, Mice, Xenograft Model Antitumor Assays.
Abstract
Honokiol (HNK), a potential antitumor compound, has been widely studied in recent years. It induces apoptosis and affects autophagy in cancer cells, yet the mechanism of its antitumor efficacy remains obscure. Chloroquine (CQ), an autophagy inhibitor, is often applied to sensitize antitumor drugs in clinical trials. Here, we investigated the antitumor effect of HNK or CQ alone or in combination in non-small cell lung cancer (NSCLC) cells. Using an experimental approach, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) or sulforhodamine B (SRB) was used to determine the cytotoxicity of the agents. The expression levels of proteins were detected by western blotting. Apoptosis was examined via Annexin V-FITC and PI staining. H460 cell xenografts in nude mice were used to study the effects of HNK and/or CQ in vivo. Transfection with siRNA was applied to knock down cathepsin D. The results demonstrated the enhanced effects of HNK combined with CQ on the inhibition of proliferation, induction of apoptosis in vitro and the reduction in growth in vivo. It was confirmed that HNK and/or CQ triggered apoptosis via a caspase-dependent manner. Furthermore, HNK significantly increased the expression of p62 and LC3-Ⅱ in the A549 and H460 cells and inhibited autophagy and induced apoptosis in a cathepsin D-involved manner. In conclusion, an enhanced antitumor effect was demonstrated following treatment with HNK combined with CQ by inhibiting autophagy and inducing apoptosis via a caspase-dependent and cathepsin D-involved manner. This combination may be a novel and useful antitumor approach for chemotherapy in NSCLC.
DOI: 10.3892/or.2015.4091
PubMed: 26136140
Affiliations:
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China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Chongwen, Beijing 100050</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Liu, Fang" sort="Liu, Fang" uniqKey="Liu F" first="Fang" last="Liu">Fang Liu</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Chongwen, Beijing 100050, P.R. China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Chongwen, Beijing 100050</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Shang, Yue" sort="Shang, Yue" uniqKey="Shang Y" first="Yue" last="Shang">Yue Shang</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Chongwen, Beijing 100050, P.R. China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Chongwen, Beijing 100050</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Chen, Shu Zhen" sort="Chen, Shu Zhen" uniqKey="Chen S" first="Shu-Zhen" last="Chen">Shu-Zhen Chen</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Chongwen, Beijing 100050, P.R. China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Chongwen, Beijing 100050</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author></analytic><series><title level="j">Oncology reports</title><idno type="eISSN">1791-2431</idno><imprint><date when="2015" type="published">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Apoptosis (drug effects)</term><term>Autophagy (drug effects)</term><term>Biphenyl Compounds (administration & dosage)</term><term>Carcinoma, Non-Small-Cell Lung (drug therapy)</term><term>Carcinoma, Non-Small-Cell Lung (pathology)</term><term>Cell Line, Tumor</term><term>Cell Proliferation (drug effects)</term><term>Chloroquine (administration & dosage)</term><term>Drug Synergism</term><term>Gene Expression Regulation, Neoplastic (drug effects)</term><term>Humans</term><term>Lignans (administration & dosage)</term><term>Mice</term><term>Neoplasm Proteins (drug effects)</term><term>Xenograft Model Antitumor Assays</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Apoptose ()</term><term>Autophagie ()</term><term>Carcinome pulmonaire non à petites cellules (anatomopathologie)</term><term>Carcinome pulmonaire non à petites cellules (traitement médicamenteux)</term><term>Chloroquine (administration et posologie)</term><term>Dérivés du biphényle (administration et posologie)</term><term>Humains</term><term>Lignanes (administration et posologie)</term><term>Lignée cellulaire tumorale</term><term>Prolifération cellulaire ()</term><term>Protéines tumorales ()</term><term>Régulation de l'expression des gènes tumoraux ()</term><term>Souris</term><term>Synergie des médicaments</term><term>Tests d'activité antitumorale sur modèle de xénogreffe</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Biphenyl Compounds</term><term>Chloroquine</term><term>Lignans</term></keywords><keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Chloroquine</term><term>Dérivés du biphényle</term><term>Lignanes</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Carcinome pulmonaire non à petites cellules</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Apoptosis</term><term>Autophagy</term><term>Cell Proliferation</term><term>Gene Expression Regulation, Neoplastic</term><term>Neoplasm Proteins</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Carcinoma, Non-Small-Cell Lung</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Carcinoma, Non-Small-Cell Lung</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Carcinome pulmonaire non à petites cellules</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cell Line, Tumor</term><term>Drug Synergism</term><term>Humans</term><term>Mice</term><term>Xenograft Model Antitumor Assays</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Apoptose</term><term>Autophagie</term><term>Humains</term><term>Lignée cellulaire tumorale</term><term>Prolifération cellulaire</term><term>Protéines tumorales</term><term>Régulation de l'expression des gènes tumoraux</term><term>Souris</term><term>Synergie des médicaments</term><term>Tests d'activité antitumorale sur modèle de xénogreffe</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Honokiol (HNK), a potential antitumor compound, has been widely studied in recent years. It induces apoptosis and affects autophagy in cancer cells, yet the mechanism of its antitumor efficacy remains obscure. Chloroquine (CQ), an autophagy inhibitor, is often applied to sensitize antitumor drugs in clinical trials. Here, we investigated the antitumor effect of HNK or CQ alone or in combination in non-small cell lung cancer (NSCLC) cells. Using an experimental approach, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) or sulforhodamine B (SRB) was used to determine the cytotoxicity of the agents. The expression levels of proteins were detected by western blotting. Apoptosis was examined via Annexin V-FITC and PI staining. H460 cell xenografts in nude mice were used to study the effects of HNK and/or CQ in vivo. Transfection with siRNA was applied to knock down cathepsin D. The results demonstrated the enhanced effects of HNK combined with CQ on the inhibition of proliferation, induction of apoptosis in vitro and the reduction in growth in vivo. It was confirmed that HNK and/or CQ triggered apoptosis via a caspase-dependent manner. Furthermore, HNK significantly increased the expression of p62 and LC3-Ⅱ in the A549 and H460 cells and inhibited autophagy and induced apoptosis in a cathepsin D-involved manner. In conclusion, an enhanced antitumor effect was demonstrated following treatment with HNK combined with CQ by inhibiting autophagy and inducing apoptosis via a caspase-dependent and cathepsin D-involved manner. This combination may be a novel and useful antitumor approach for chemotherapy in NSCLC. </div></front></TEI><affiliations><list><country><li>République populaire de Chine</li></country><settlement><li>Pékin</li></settlement></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Lv, Xiaoqin" sort="Lv, Xiaoqin" uniqKey="Lv X" first="Xiaoqin" last="Lv">Xiaoqin Lv</name></noRegion><name sortKey="Chen, Shu Zhen" sort="Chen, Shu Zhen" uniqKey="Chen S" first="Shu-Zhen" last="Chen">Shu-Zhen Chen</name><name sortKey="Liu, Fang" sort="Liu, Fang" uniqKey="Liu F" first="Fang" last="Liu">Fang Liu</name><name sortKey="Shang, Yue" sort="Shang, Yue" uniqKey="Shang Y" first="Yue" last="Shang">Yue Shang</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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