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Autophagy inhibition enhances isorhamnetin‑induced mitochondria‑dependent apoptosis in non‑small cell lung cancer cells.

Identifieur interne : 000F01 ( Main/Exploration ); précédent : 000F00; suivant : 000F02

Autophagy inhibition enhances isorhamnetin‑induced mitochondria‑dependent apoptosis in non‑small cell lung cancer cells.

Auteurs : Yushu Ruan [République populaire de Chine] ; Ke Hu [République populaire de Chine] ; Hongbo Chen [République populaire de Chine]

Source :

RBID : pubmed:26238746

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English descriptors

Abstract

Isorhamnetin (ISO) is a flavonoid from plants of the Polygonaceae family and is also an immediate metabolite of quercetin in mammals. To date, the anti‑tumor effects of ISO and the underlying mechanisms have not been elucidated in lung cancer cells. The present study investigated the inhibitory effects of ISO on the growth of human lung cancer A549 cells. Treatment of the lung cancer cells with ISO significantly suppressed cell proliferation and colony formation. ISO treatment also resulted in a significant increase in apoptotic cell death of A549 cells in a time- and dose-dependent manner. Further investigation showed that the apoptosis proceeded via the mitochondria‑dependent pathway as indicated by alteration of the mitochondrial membrane potential, the release of cytochrome C and caspase activation. Of note, treatment with ISO also induced the formation of autophagosomes and light chain 3‑II protein in A549 cells. Furthermore, co‑treatment with autophagy inhibitors 3‑methyladenine and hydroxychloroquine significantly inhibited the ISO‑induced autophagy and enhanced the ISO‑induced apoptotic cell death in vitro as well as in vivo. Thus, the results of the present study suggested that ISO is a potential anti‑lung cancer agent. In addition, the results indicated that the inhibition of autophagy may be a useful strategy for enhancing the chemotherapeutic effect of ISO on lung cancer cells.

DOI: 10.3892/mmr.2015.4148
PubMed: 26238746


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<term>Adenine (pharmacology)</term>
<term>Animals</term>
<term>Antineoplastic Agents, Phytogenic (pharmacology)</term>
<term>Apoptosis (drug effects)</term>
<term>Autophagy (drug effects)</term>
<term>Carcinoma, Non-Small-Cell Lung (drug therapy)</term>
<term>Carcinoma, Non-Small-Cell Lung (genetics)</term>
<term>Carcinoma, Non-Small-Cell Lung (metabolism)</term>
<term>Carcinoma, Non-Small-Cell Lung (pathology)</term>
<term>Caspases (genetics)</term>
<term>Caspases (metabolism)</term>
<term>Cell Line, Tumor</term>
<term>Cell Proliferation (drug effects)</term>
<term>Cytochromes c (metabolism)</term>
<term>Dose-Response Relationship, Drug</term>
<term>Drug Synergism</term>
<term>Epithelial Cells (drug effects)</term>
<term>Epithelial Cells (metabolism)</term>
<term>Epithelial Cells (pathology)</term>
<term>Gene Expression</term>
<term>Humans</term>
<term>Hydroxychloroquine (pharmacology)</term>
<term>Lung Neoplasms (drug therapy)</term>
<term>Lung Neoplasms (genetics)</term>
<term>Lung Neoplasms (metabolism)</term>
<term>Lung Neoplasms (pathology)</term>
<term>Membrane Potential, Mitochondrial (drug effects)</term>
<term>Mice</term>
<term>Mice, Nude</term>
<term>Microtubule-Associated Proteins (genetics)</term>
<term>Microtubule-Associated Proteins (metabolism)</term>
<term>Mitochondria (drug effects)</term>
<term>Mitochondria (metabolism)</term>
<term>Quercetin (analogs & derivatives)</term>
<term>Quercetin (pharmacology)</term>
<term>Xenograft Model Antitumor Assays</term>
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<term>Animaux</term>
<term>Antinéoplasiques d'origine végétale (pharmacologie)</term>
<term>Apoptose ()</term>
<term>Autophagie ()</term>
<term>Carcinome pulmonaire non à petites cellules (anatomopathologie)</term>
<term>Carcinome pulmonaire non à petites cellules (génétique)</term>
<term>Carcinome pulmonaire non à petites cellules (métabolisme)</term>
<term>Carcinome pulmonaire non à petites cellules (traitement médicamenteux)</term>
<term>Caspases (génétique)</term>
<term>Caspases (métabolisme)</term>
<term>Cellules épithéliales ()</term>
<term>Cellules épithéliales (anatomopathologie)</term>
<term>Cellules épithéliales (métabolisme)</term>
<term>Cytochromes c (métabolisme)</term>
<term>Expression des gènes</term>
<term>Humains</term>
<term>Hydroxychloroquine (pharmacologie)</term>
<term>Lignée cellulaire tumorale</term>
<term>Mitochondries ()</term>
<term>Mitochondries (métabolisme)</term>
<term>Potentiel de membrane mitochondriale ()</term>
<term>Prolifération cellulaire ()</term>
<term>Protéines associées aux microtubules (génétique)</term>
<term>Protéines associées aux microtubules (métabolisme)</term>
<term>Quercétine (analogues et dérivés)</term>
<term>Quercétine (pharmacologie)</term>
<term>Relation dose-effet des médicaments</term>
<term>Souris</term>
<term>Souris nude</term>
<term>Synergie des médicaments</term>
<term>Tests d'activité antitumorale sur modèle de xénogreffe</term>
<term>Tumeurs du poumon (anatomopathologie)</term>
<term>Tumeurs du poumon (génétique)</term>
<term>Tumeurs du poumon (métabolisme)</term>
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<term>Quercetin</term>
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<term>Microtubule-Associated Proteins</term>
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<term>Caspases</term>
<term>Cytochromes c</term>
<term>Microtubule-Associated Proteins</term>
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<term>Adenine</term>
<term>Antineoplastic Agents, Phytogenic</term>
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<term>Quercetin</term>
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<term>Carcinome pulmonaire non à petites cellules</term>
<term>Cellules épithéliales</term>
<term>Tumeurs du poumon</term>
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<term>Apoptosis</term>
<term>Autophagy</term>
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<term>Apoptose</term>
<term>Autophagie</term>
<term>Cellules épithéliales</term>
<term>Expression des gènes</term>
<term>Humains</term>
<term>Lignée cellulaire tumorale</term>
<term>Mitochondries</term>
<term>Potentiel de membrane mitochondriale</term>
<term>Prolifération cellulaire</term>
<term>Relation dose-effet des médicaments</term>
<term>Souris</term>
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<front>
<div type="abstract" xml:lang="en">Isorhamnetin (ISO) is a flavonoid from plants of the Polygonaceae family and is also an immediate metabolite of quercetin in mammals. To date, the anti‑tumor effects of ISO and the underlying mechanisms have not been elucidated in lung cancer cells. The present study investigated the inhibitory effects of ISO on the growth of human lung cancer A549 cells. Treatment of the lung cancer cells with ISO significantly suppressed cell proliferation and colony formation. ISO treatment also resulted in a significant increase in apoptotic cell death of A549 cells in a time- and dose-dependent manner. Further investigation showed that the apoptosis proceeded via the mitochondria‑dependent pathway as indicated by alteration of the mitochondrial membrane potential, the release of cytochrome C and caspase activation. Of note, treatment with ISO also induced the formation of autophagosomes and light chain 3‑II protein in A549 cells. Furthermore, co‑treatment with autophagy inhibitors 3‑methyladenine and hydroxychloroquine significantly inhibited the ISO‑induced autophagy and enhanced the ISO‑induced apoptotic cell death in vitro as well as in vivo. Thus, the results of the present study suggested that ISO is a potential anti‑lung cancer agent. In addition, the results indicated that the inhibition of autophagy may be a useful strategy for enhancing the chemotherapeutic effect of ISO on lung cancer cells.</div>
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