ChloroquineV1, Main, Exploration, bibRecord, 000C22

Novel dihydroartemisinin derivative DHA-37 induces autophagic cell death through upregulation of HMGB1 in A549 cells.

Identifieur interne : 000C22 ( Main/Exploration ); précédent : 000C21; suivant : 000C23

Novel dihydroartemisinin derivative DHA-37 induces autophagic cell death through upregulation of HMGB1 in A549 cells.

Auteurs : Xiufeng Liu [République populaire de Chine] ; Juanjuan Wu [République populaire de Chine] ; Menglin Fan [République populaire de Chine] ; Chen Shen [République populaire de Chine] ; Wenling Dai [République populaire de Chine] ; Yini Bao [République populaire de Chine] ; Ji-Hua Liu [République populaire de Chine] ; Bo-Yang Yu [République populaire de Chine]

Source :

Cell death & disease [ 2041-4889 ] ; 2018.

RBID : pubmed:30323180

Descripteurs français

English descriptors

KwdEn :
- A549 Cells, Adenocarcinoma, Bronchiolo-Alveolar (drug therapy), Adenocarcinoma, Bronchiolo-Alveolar (genetics), Adenocarcinoma, Bronchiolo-Alveolar (metabolism), Adenocarcinoma, Bronchiolo-Alveolar (pathology), Animals, Antineoplastic Agents, Phytogenic (chemical synthesis), Antineoplastic Agents, Phytogenic (pharmacology), Artemisinins (chemical synthesis), Artemisinins (pharmacology), Autophagy (drug effects), Autophagy (genetics), Cell Cycle (drug effects), Cell Cycle (genetics), Gene Expression Regulation, Neoplastic, HMGB1 Protein (antagonists & inhibitors), HMGB1 Protein (genetics), HMGB1 Protein (metabolism), Humans, Lung Neoplasms (drug therapy), Lung Neoplasms (genetics), Lung Neoplasms (metabolism), Lung Neoplasms (pathology), Male, Mice, Mice, Nude, Microtubule-Associated Proteins (genetics), Microtubule-Associated Proteins (metabolism), Mitogen-Activated Protein Kinase 1 (genetics), Mitogen-Activated Protein Kinase 1 (metabolism), Mitogen-Activated Protein Kinase 3 (genetics), Mitogen-Activated Protein Kinase 3 (metabolism), Mitogen-Activated Protein Kinase 8 (genetics), Mitogen-Activated Protein Kinase 8 (metabolism), RNA, Small Interfering (genetics), RNA, Small Interfering (metabolism), Signal Transduction, Tumor Burden (drug effects), Vacuoles (drug effects), Vacuoles (metabolism), Vacuoles (ultrastructure), Xenograft Model Antitumor Assays.
MESH :
- chemical , antagonists & inhibitors : HMGB1 Protein.
- chemical , chemical synthesis : Antineoplastic Agents, Phytogenic, Artemisinins.
- drug effects : Autophagy, Cell Cycle, Tumor Burden, Vacuoles.
- drug therapy : Adenocarcinoma, Bronchiolo-Alveolar, Lung Neoplasms.
- genetics : Adenocarcinoma, Bronchiolo-Alveolar, Autophagy, Cell Cycle, HMGB1 Protein, Lung Neoplasms, Microtubule-Associated Proteins, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, Mitogen-Activated Protein Kinase 8, RNA, Small Interfering.
- metabolism : Adenocarcinoma, Bronchiolo-Alveolar, HMGB1 Protein, Lung Neoplasms, Microtubule-Associated Proteins, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, Mitogen-Activated Protein Kinase 8, RNA, Small Interfering, Vacuoles.
- pathology : Adenocarcinoma, Bronchiolo-Alveolar, Lung Neoplasms.
- chemical , pharmacology : Antineoplastic Agents, Phytogenic, Artemisinins.
- ultrastructure : Vacuoles.
- A549 Cells, Animals, Gene Expression Regulation, Neoplastic, Humans, Male, Mice, Mice, Nude, Signal Transduction, Xenograft Model Antitumor Assays.

Abstract

Dihydroartemisinin (DHA) and its analogs are reported to possess selective anticancer activity. Here, we reported a novel DHA derivative DHA-37 that exhibited more potent anticancer activity on the cells tested. Distinct from DHA-induced apoptosis, DHA-37 triggered excessive autophagic cell death, and became the main contributor to DHA-37-induced A549 cell death. Incubation of the cells with DHA-37 but not DHA produced increased dots distribution of GFP-LC3 and expression ratio of LC3-II/LC3-I, and enhanced the formation of autophagic vacuoles as revealed by TEM. Treatment with the autophagy inhibitor 3-MA, LY294002, or chloroquine could reverse DHA-37-induced cell death. In addition, DHA-37-induced cell death was associated significantly with the increased expression of HMGB1, and knockdown of HMGB1 could reverse DHA-37-induced cell death. More importantly, the elevated HMGB1 expression induced autophagy through the activation of the MAPK signal but not PI3K-AKT-mTOR pathway. In addition, DHA-37 also showed a wonderful performance in A549 xenograft mice model. These findings suggest that HMGB1 as a target candidate for apoptosis-resistant cancer treatment and artemisinin-based drugs could be used in inducing autophagic cell death.

DOI: 10.1038/s41419-018-1006-y
PubMed: 30323180

Affiliations:

République populaire de Chine

Le document en format XML

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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>A549 Cells</term>
<term>Adenocarcinoma, Bronchiolo-Alveolar (drug therapy)</term>
<term>Adenocarcinoma, Bronchiolo-Alveolar (genetics)</term>
<term>Adenocarcinoma, Bronchiolo-Alveolar (metabolism)</term>
<term>Adenocarcinoma, Bronchiolo-Alveolar (pathology)</term>
<term>Animals</term>
<term>Antineoplastic Agents, Phytogenic (chemical synthesis)</term>
<term>Antineoplastic Agents, Phytogenic (pharmacology)</term>
<term>Artemisinins (chemical synthesis)</term>
<term>Artemisinins (pharmacology)</term>
<term>Autophagy (drug effects)</term>
<term>Autophagy (genetics)</term>
<term>Cell Cycle (drug effects)</term>
<term>Cell Cycle (genetics)</term>
<term>Gene Expression Regulation, Neoplastic</term>
<term>HMGB1 Protein (antagonists & inhibitors)</term>
<term>HMGB1 Protein (genetics)</term>
<term>HMGB1 Protein (metabolism)</term>
<term>Humans</term>
<term>Lung Neoplasms (drug therapy)</term>
<term>Lung Neoplasms (genetics)</term>
<term>Lung Neoplasms (metabolism)</term>
<term>Lung Neoplasms (pathology)</term>
<term>Male</term>
<term>Mice</term>
<term>Mice, Nude</term>
<term>Microtubule-Associated Proteins (genetics)</term>
<term>Microtubule-Associated Proteins (metabolism)</term>
<term>Mitogen-Activated Protein Kinase 1 (genetics)</term>
<term>Mitogen-Activated Protein Kinase 1 (metabolism)</term>
<term>Mitogen-Activated Protein Kinase 3 (genetics)</term>
<term>Mitogen-Activated Protein Kinase 3 (metabolism)</term>
<term>Mitogen-Activated Protein Kinase 8 (genetics)</term>
<term>Mitogen-Activated Protein Kinase 8 (metabolism)</term>
<term>RNA, Small Interfering (genetics)</term>
<term>RNA, Small Interfering (metabolism)</term>
<term>Signal Transduction</term>
<term>Tumor Burden (drug effects)</term>
<term>Vacuoles (drug effects)</term>
<term>Vacuoles (metabolism)</term>
<term>Vacuoles (ultrastructure)</term>
<term>Xenograft Model Antitumor Assays</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Adénocarcinome bronchioloalvéolaire (anatomopathologie)</term>
<term>Adénocarcinome bronchioloalvéolaire (génétique)</term>
<term>Adénocarcinome bronchioloalvéolaire (métabolisme)</term>
<term>Adénocarcinome bronchioloalvéolaire (traitement médicamenteux)</term>
<term>Animaux</term>
<term>Antinéoplasiques d'origine végétale (pharmacologie)</term>
<term>Antinéoplasiques d'origine végétale (synthèse chimique)</term>
<term>Artémisinines (pharmacologie)</term>
<term>Artémisinines (synthèse chimique)</term>
<term>Autophagie ()</term>
<term>Autophagie (génétique)</term>
<term>Cellules A549</term>
<term>Charge tumorale ()</term>
<term>Cycle cellulaire ()</term>
<term>Cycle cellulaire (génétique)</term>
<term>Humains</term>
<term>Mitogen-Activated Protein Kinase 1 (génétique)</term>
<term>Mitogen-Activated Protein Kinase 1 (métabolisme)</term>
<term>Mitogen-Activated Protein Kinase 3 (génétique)</term>
<term>Mitogen-Activated Protein Kinase 3 (métabolisme)</term>
<term>Mitogen-Activated Protein Kinase 8 (génétique)</term>
<term>Mitogen-Activated Protein Kinase 8 (métabolisme)</term>
<term>Mâle</term>
<term>Petit ARN interférent (génétique)</term>
<term>Petit ARN interférent (métabolisme)</term>
<term>Protéine HMGB1 (antagonistes et inhibiteurs)</term>
<term>Protéine HMGB1 (génétique)</term>
<term>Protéine HMGB1 (métabolisme)</term>
<term>Protéines associées aux microtubules (génétique)</term>
<term>Protéines associées aux microtubules (métabolisme)</term>
<term>Régulation de l'expression des gènes tumoraux</term>
<term>Souris</term>
<term>Souris nude</term>
<term>Tests d'activité antitumorale sur modèle de xénogreffe</term>
<term>Transduction du signal</term>
<term>Tumeurs du poumon (anatomopathologie)</term>
<term>Tumeurs du poumon (génétique)</term>
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<term>Vacuoles (ultrastructure)</term>
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<term>Artemisinins</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Adénocarcinome bronchioloalvéolaire</term>
<term>Tumeurs du poumon</term>
</keywords>
<keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Protéine HMGB1</term>
</keywords>
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<term>Cell Cycle</term>
<term>Tumor Burden</term>
<term>Vacuoles</term>
</keywords>
<keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Adenocarcinoma, Bronchiolo-Alveolar</term>
<term>Lung Neoplasms</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Adenocarcinoma, Bronchiolo-Alveolar</term>
<term>Autophagy</term>
<term>Cell Cycle</term>
<term>HMGB1 Protein</term>
<term>Lung Neoplasms</term>
<term>Microtubule-Associated Proteins</term>
<term>Mitogen-Activated Protein Kinase 1</term>
<term>Mitogen-Activated Protein Kinase 3</term>
<term>Mitogen-Activated Protein Kinase 8</term>
<term>RNA, Small Interfering</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Adénocarcinome bronchioloalvéolaire</term>
<term>Autophagie</term>
<term>Cycle cellulaire</term>
<term>Mitogen-Activated Protein Kinase 1</term>
<term>Mitogen-Activated Protein Kinase 3</term>
<term>Mitogen-Activated Protein Kinase 8</term>
<term>Petit ARN interférent</term>
<term>Protéine HMGB1</term>
<term>Protéines associées aux microtubules</term>
<term>Tumeurs du poumon</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Adenocarcinoma, Bronchiolo-Alveolar</term>
<term>HMGB1 Protein</term>
<term>Lung Neoplasms</term>
<term>Microtubule-Associated Proteins</term>
<term>Mitogen-Activated Protein Kinase 1</term>
<term>Mitogen-Activated Protein Kinase 3</term>
<term>Mitogen-Activated Protein Kinase 8</term>
<term>RNA, Small Interfering</term>
<term>Vacuoles</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Adénocarcinome bronchioloalvéolaire</term>
<term>Mitogen-Activated Protein Kinase 1</term>
<term>Mitogen-Activated Protein Kinase 3</term>
<term>Mitogen-Activated Protein Kinase 8</term>
<term>Petit ARN interférent</term>
<term>Protéine HMGB1</term>
<term>Protéines associées aux microtubules</term>
<term>Tumeurs du poumon</term>
<term>Vacuoles</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Adenocarcinoma, Bronchiolo-Alveolar</term>
<term>Lung Neoplasms</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Antinéoplasiques d'origine végétale</term>
<term>Artémisinines</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antineoplastic Agents, Phytogenic</term>
<term>Artemisinins</term>
</keywords>
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<term>Artémisinines</term>
</keywords>
<keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Adénocarcinome bronchioloalvéolaire</term>
<term>Tumeurs du poumon</term>
</keywords>
<keywords scheme="MESH" qualifier="ultrastructure" xml:lang="en"><term>Vacuoles</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>A549 Cells</term>
<term>Animals</term>
<term>Gene Expression Regulation, Neoplastic</term>
<term>Humans</term>
<term>Male</term>
<term>Mice</term>
<term>Mice, Nude</term>
<term>Signal Transduction</term>
<term>Xenograft Model Antitumor Assays</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Animaux</term>
<term>Autophagie</term>
<term>Cellules A549</term>
<term>Charge tumorale</term>
<term>Cycle cellulaire</term>
<term>Humains</term>
<term>Mâle</term>
<term>Régulation de l'expression des gènes tumoraux</term>
<term>Souris</term>
<term>Souris nude</term>
<term>Tests d'activité antitumorale sur modèle de xénogreffe</term>
<term>Transduction du signal</term>
<term>Vacuoles</term>
</keywords>
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<front><div type="abstract" xml:lang="en">Dihydroartemisinin (DHA) and its analogs are reported to possess selective anticancer activity. Here, we reported a novel DHA derivative DHA-37 that exhibited more potent anticancer activity on the cells tested. Distinct from DHA-induced apoptosis, DHA-37 triggered excessive autophagic cell death, and became the main contributor to DHA-37-induced A549 cell death. Incubation of the cells with DHA-37 but not DHA produced increased dots distribution of GFP-LC3 and expression ratio of LC3-II/LC3-I, and enhanced the formation of autophagic vacuoles as revealed by TEM. Treatment with the autophagy inhibitor 3-MA, LY294002, or chloroquine could reverse DHA-37-induced cell death. In addition, DHA-37-induced cell death was associated significantly with the increased expression of HMGB1, and knockdown of HMGB1 could reverse DHA-37-induced cell death. More importantly, the elevated HMGB1 expression induced autophagy through the activation of the MAPK signal but not PI3K-AKT-mTOR pathway. In addition, DHA-37 also showed a wonderful performance in A549 xenograft mice model. These findings suggest that HMGB1 as a target candidate for apoptosis-resistant cancer treatment and artemisinin-based drugs could be used in inducing autophagic cell death.</div>
</front>
</TEI>
<affiliations><list><country><li>République populaire de Chine</li>
</country>
</list>
<tree><country name="République populaire de Chine"><noRegion><name sortKey="Liu, Xiufeng" sort="Liu, Xiufeng" uniqKey="Liu X" first="Xiufeng" last="Liu">Xiufeng Liu</name>
</noRegion>
<name sortKey="Bao, Yini" sort="Bao, Yini" uniqKey="Bao Y" first="Yini" last="Bao">Yini Bao</name>
<name sortKey="Dai, Wenling" sort="Dai, Wenling" uniqKey="Dai W" first="Wenling" last="Dai">Wenling Dai</name>
<name sortKey="Fan, Menglin" sort="Fan, Menglin" uniqKey="Fan M" first="Menglin" last="Fan">Menglin Fan</name>
<name sortKey="Liu, Ji Hua" sort="Liu, Ji Hua" uniqKey="Liu J" first="Ji-Hua" last="Liu">Ji-Hua Liu</name>
<name sortKey="Shen, Chen" sort="Shen, Chen" uniqKey="Shen C" first="Chen" last="Shen">Chen Shen</name>
<name sortKey="Wu, Juanjuan" sort="Wu, Juanjuan" uniqKey="Wu J" first="Juanjuan" last="Wu">Juanjuan Wu</name>
<name sortKey="Yu, Bo Yang" sort="Yu, Bo Yang" uniqKey="Yu B" first="Bo-Yang" last="Yu">Bo-Yang Yu</name>
</country>
</tree>
</affiliations>
</record>

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Novel dihydroartemisinin derivative DHA-37 induces autophagic cell death through upregulation of HMGB1 in A549 cells.

Novel dihydroartemisinin derivative DHA-37 induces autophagic cell death through upregulation of HMGB1 in A549 cells.

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