Growth inhibitory role of the p53 activator SCH 529074 in non‑small cell lung cancer cells expressing mutant p53.
Identifieur interne : 000146 ( Main/Exploration ); précédent : 000145; suivant : 000147Growth inhibitory role of the p53 activator SCH 529074 in non‑small cell lung cancer cells expressing mutant p53.
Auteurs : Miljana Nenkov [Allemagne] ; Yunxia Ma [Allemagne] ; Daniela Haase [Allemagne] ; Zhongwei Zhou [Allemagne] ; Yong Li [Allemagne] ; Iver Petersen [Allemagne] ; Guanghua Lu [République populaire de Chine] ; Yuan Chen [Allemagne]Source :
- Oncology reports [ 1791-2431 ] ; 2020.
Abstract
Mutations of p53 occur in approximately 50% of advanced non‑small cell lung cancer (NSCLC) cases, leading to loss of tumor suppressive function and/or gain of p53 oncogenic activity. Reactivation of mutant p53 and consequently induction of apoptosis in cancer cells is the goal of p53‑targeted therapy. Recently, several p53 mutant reactivating compounds were discovered including SCH 529074. However, the role of SCH 529074 in NSCLC has not been fully explored. In the present study, the effects of this compound on cell survival, cell cycle progression, induction of apoptosis and modulation of cell signaling in p53 mutant NSCLC cells (H1975, H322 and H157) and p53 wild‑type NSCLC cells (A549), was investigated. Cell‑based functional assays, real‑time RT‑qPCR and western blot assays were used. HCT116 [p53 wild‑type (WT)] and HCT116 p53‑/‑ (p53 null) were used as control cells. The results demonstrated that SCH 529074 treatment caused significant reduction in cell viability and colony formation activity in p53 mutant, p53 WT and p53‑deficient cells. The treatment of NSCLC cells with SCH 529074 resulted in a dose‑dependent induction of apoptosis and G0/G1 cell cycle arrest, which was associated with the activation of caspases (3 and 7), p53‑independent upregulation of p21 and PUMA as well as increased LC3II, a biomarker of autophagy. The combination treatment with the autophagy inhibitor chloroquine (CQ) and SCH 529074 led to decreased cell viability, colony formation and increased induction of apoptosis. The data indicated that SCH 529074 may exert its growth inhibitory function in a p53‑independent manner in NSCLC cells.
DOI: 10.3892/or.2020.7546
PubMed: 32186773
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: 000001
- to stream PubMed, to step Curation: 000001
- to stream PubMed, to step Checkpoint: 000006
- to stream Ncbi, to step Merge: 001033
- to stream Ncbi, to step Curation: 001033
- to stream Ncbi, to step Checkpoint: 001033
- to stream Main, to step Merge: 000146
- to stream Main, to step Curation: 000146
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Growth inhibitory role of the p53 activator SCH 529074 in non‑small cell lung cancer cells expressing mutant p53.</title><author><name sortKey="Nenkov, Miljana" sort="Nenkov, Miljana" uniqKey="Nenkov M" first="Miljana" last="Nenkov">Miljana Nenkov</name><affiliation wicri:level="1"><nlm:affiliation>Section Pathology of The Institute of Forensic Medicine, University Hospital Jena, Friedrich Schiller University, D‑07747 Jena, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Section Pathology of The Institute of Forensic Medicine, University Hospital Jena, Friedrich Schiller University, D‑07747 Jena</wicri:regionArea><wicri:noRegion>07747 Jena</wicri:noRegion><wicri:noRegion>07747 Jena</wicri:noRegion><wicri:noRegion>D‑07747 Jena</wicri:noRegion></affiliation></author><author><name sortKey="Ma, Yunxia" sort="Ma, Yunxia" uniqKey="Ma Y" first="Yunxia" last="Ma">Yunxia Ma</name><affiliation wicri:level="1"><nlm:affiliation>Section Pathology of The Institute of Forensic Medicine, University Hospital Jena, Friedrich Schiller University, D‑07747 Jena, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Section Pathology of The Institute of Forensic Medicine, University Hospital Jena, Friedrich Schiller University, D‑07747 Jena</wicri:regionArea><wicri:noRegion>07747 Jena</wicri:noRegion><wicri:noRegion>07747 Jena</wicri:noRegion><wicri:noRegion>D‑07747 Jena</wicri:noRegion></affiliation></author><author><name sortKey="Haase, Daniela" sort="Haase, Daniela" uniqKey="Haase D" first="Daniela" last="Haase">Daniela Haase</name><affiliation wicri:level="1"><nlm:affiliation>Section Pathology of The Institute of Forensic Medicine, University Hospital Jena, Friedrich Schiller University, D‑07747 Jena, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Section Pathology of The Institute of Forensic Medicine, University Hospital Jena, Friedrich Schiller University, D‑07747 Jena</wicri:regionArea><wicri:noRegion>07747 Jena</wicri:noRegion><wicri:noRegion>07747 Jena</wicri:noRegion><wicri:noRegion>D‑07747 Jena</wicri:noRegion></affiliation></author><author><name sortKey="Zhou, Zhongwei" sort="Zhou, Zhongwei" uniqKey="Zhou Z" first="Zhongwei" last="Zhou">Zhongwei Zhou</name><affiliation wicri:level="1"><nlm:affiliation>Leibniz Institute on Ageing‑Fritz Lipmann Institute (FLI), D‑07745 Jena, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Leibniz Institute on Ageing‑Fritz Lipmann Institute (FLI), D‑07745 Jena</wicri:regionArea><wicri:noRegion>07745 Jena</wicri:noRegion><wicri:noRegion>07745 Jena</wicri:noRegion><wicri:noRegion>D‑07745 Jena</wicri:noRegion></affiliation></author><author><name sortKey="Li, Yong" sort="Li, Yong" uniqKey="Li Y" first="Yong" last="Li">Yong Li</name><affiliation wicri:level="1"><nlm:affiliation>Section Pathology of The Institute of Forensic Medicine, University Hospital Jena, Friedrich Schiller University, D‑07747 Jena, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Section Pathology of The Institute of Forensic Medicine, University Hospital Jena, Friedrich Schiller University, D‑07747 Jena</wicri:regionArea><wicri:noRegion>07747 Jena</wicri:noRegion><wicri:noRegion>07747 Jena</wicri:noRegion><wicri:noRegion>D‑07747 Jena</wicri:noRegion></affiliation></author><author><name sortKey="Petersen, Iver" sort="Petersen, Iver" uniqKey="Petersen I" first="Iver" last="Petersen">Iver Petersen</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Pathology, SRH Wald‑Klinikum, D‑07548 Gera, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Pathology, SRH Wald‑Klinikum, D‑07548 Gera</wicri:regionArea><wicri:noRegion>07548 Gera</wicri:noRegion><wicri:noRegion>07548 Gera</wicri:noRegion><wicri:noRegion>D‑07548 Gera</wicri:noRegion></affiliation></author><author><name sortKey="Lu, Guanghua" sort="Lu, Guanghua" uniqKey="Lu G" first="Guanghua" last="Lu">Guanghua Lu</name><affiliation wicri:level="1"><nlm:affiliation>School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, P.R. China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137</wicri:regionArea><wicri:noRegion>Sichuan 611137</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Yuan" sort="Chen, Yuan" uniqKey="Chen Y" first="Yuan" last="Chen">Yuan Chen</name><affiliation wicri:level="1"><nlm:affiliation>Section Pathology of The Institute of Forensic Medicine, University Hospital Jena, Friedrich Schiller University, D‑07747 Jena, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Section Pathology of The Institute of Forensic Medicine, University Hospital Jena, Friedrich Schiller University, D‑07747 Jena</wicri:regionArea><wicri:noRegion>07747 Jena</wicri:noRegion><wicri:noRegion>07747 Jena</wicri:noRegion><wicri:noRegion>D‑07747 Jena</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2020">2020</date><idno type="RBID">pubmed:32186773</idno><idno type="pmid">32186773</idno><idno type="doi">10.3892/or.2020.7546</idno><idno type="wicri:Area/PubMed/Corpus">000001</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000001</idno><idno type="wicri:Area/PubMed/Curation">000001</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000001</idno><idno type="wicri:Area/PubMed/Checkpoint">000006</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000006</idno><idno type="wicri:Area/Ncbi/Merge">001033</idno><idno type="wicri:Area/Ncbi/Curation">001033</idno><idno type="wicri:Area/Ncbi/Checkpoint">001033</idno><idno type="wicri:Area/Main/Merge">000146</idno><idno type="wicri:Area/Main/Curation">000146</idno><idno type="wicri:Area/Main/Exploration">000146</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Growth inhibitory role of the p53 activator SCH 529074 in non‑small cell lung cancer cells expressing mutant p53.</title><author><name sortKey="Nenkov, Miljana" sort="Nenkov, Miljana" uniqKey="Nenkov M" first="Miljana" last="Nenkov">Miljana Nenkov</name><affiliation wicri:level="1"><nlm:affiliation>Section Pathology of The Institute of Forensic Medicine, University Hospital Jena, Friedrich Schiller University, D‑07747 Jena, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Section Pathology of The Institute of Forensic Medicine, University Hospital Jena, Friedrich Schiller University, D‑07747 Jena</wicri:regionArea><wicri:noRegion>07747 Jena</wicri:noRegion><wicri:noRegion>07747 Jena</wicri:noRegion><wicri:noRegion>D‑07747 Jena</wicri:noRegion></affiliation></author><author><name sortKey="Ma, Yunxia" sort="Ma, Yunxia" uniqKey="Ma Y" first="Yunxia" last="Ma">Yunxia Ma</name><affiliation wicri:level="1"><nlm:affiliation>Section Pathology of The Institute of Forensic Medicine, University Hospital Jena, Friedrich Schiller University, D‑07747 Jena, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Section Pathology of The Institute of Forensic Medicine, University Hospital Jena, Friedrich Schiller University, D‑07747 Jena</wicri:regionArea><wicri:noRegion>07747 Jena</wicri:noRegion><wicri:noRegion>07747 Jena</wicri:noRegion><wicri:noRegion>D‑07747 Jena</wicri:noRegion></affiliation></author><author><name sortKey="Haase, Daniela" sort="Haase, Daniela" uniqKey="Haase D" first="Daniela" last="Haase">Daniela Haase</name><affiliation wicri:level="1"><nlm:affiliation>Section Pathology of The Institute of Forensic Medicine, University Hospital Jena, Friedrich Schiller University, D‑07747 Jena, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Section Pathology of The Institute of Forensic Medicine, University Hospital Jena, Friedrich Schiller University, D‑07747 Jena</wicri:regionArea><wicri:noRegion>07747 Jena</wicri:noRegion><wicri:noRegion>07747 Jena</wicri:noRegion><wicri:noRegion>D‑07747 Jena</wicri:noRegion></affiliation></author><author><name sortKey="Zhou, Zhongwei" sort="Zhou, Zhongwei" uniqKey="Zhou Z" first="Zhongwei" last="Zhou">Zhongwei Zhou</name><affiliation wicri:level="1"><nlm:affiliation>Leibniz Institute on Ageing‑Fritz Lipmann Institute (FLI), D‑07745 Jena, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Leibniz Institute on Ageing‑Fritz Lipmann Institute (FLI), D‑07745 Jena</wicri:regionArea><wicri:noRegion>07745 Jena</wicri:noRegion><wicri:noRegion>07745 Jena</wicri:noRegion><wicri:noRegion>D‑07745 Jena</wicri:noRegion></affiliation></author><author><name sortKey="Li, Yong" sort="Li, Yong" uniqKey="Li Y" first="Yong" last="Li">Yong Li</name><affiliation wicri:level="1"><nlm:affiliation>Section Pathology of The Institute of Forensic Medicine, University Hospital Jena, Friedrich Schiller University, D‑07747 Jena, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Section Pathology of The Institute of Forensic Medicine, University Hospital Jena, Friedrich Schiller University, D‑07747 Jena</wicri:regionArea><wicri:noRegion>07747 Jena</wicri:noRegion><wicri:noRegion>07747 Jena</wicri:noRegion><wicri:noRegion>D‑07747 Jena</wicri:noRegion></affiliation></author><author><name sortKey="Petersen, Iver" sort="Petersen, Iver" uniqKey="Petersen I" first="Iver" last="Petersen">Iver Petersen</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Pathology, SRH Wald‑Klinikum, D‑07548 Gera, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Pathology, SRH Wald‑Klinikum, D‑07548 Gera</wicri:regionArea><wicri:noRegion>07548 Gera</wicri:noRegion><wicri:noRegion>07548 Gera</wicri:noRegion><wicri:noRegion>D‑07548 Gera</wicri:noRegion></affiliation></author><author><name sortKey="Lu, Guanghua" sort="Lu, Guanghua" uniqKey="Lu G" first="Guanghua" last="Lu">Guanghua Lu</name><affiliation wicri:level="1"><nlm:affiliation>School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, P.R. China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137</wicri:regionArea><wicri:noRegion>Sichuan 611137</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Yuan" sort="Chen, Yuan" uniqKey="Chen Y" first="Yuan" last="Chen">Yuan Chen</name><affiliation wicri:level="1"><nlm:affiliation>Section Pathology of The Institute of Forensic Medicine, University Hospital Jena, Friedrich Schiller University, D‑07747 Jena, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Section Pathology of The Institute of Forensic Medicine, University Hospital Jena, Friedrich Schiller University, D‑07747 Jena</wicri:regionArea><wicri:noRegion>07747 Jena</wicri:noRegion><wicri:noRegion>07747 Jena</wicri:noRegion><wicri:noRegion>D‑07747 Jena</wicri:noRegion></affiliation></author></analytic><series><title level="j">Oncology reports</title><idno type="eISSN">1791-2431</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Mutations of p53 occur in approximately 50% of advanced non‑small cell lung cancer (NSCLC) cases, leading to loss of tumor suppressive function and/or gain of p53 oncogenic activity. Reactivation of mutant p53 and consequently induction of apoptosis in cancer cells is the goal of p53‑targeted therapy. Recently, several p53 mutant reactivating compounds were discovered including SCH 529074. However, the role of SCH 529074 in NSCLC has not been fully explored. In the present study, the effects of this compound on cell survival, cell cycle progression, induction of apoptosis and modulation of cell signaling in p53 mutant NSCLC cells (H1975, H322 and H157) and p53 wild‑type NSCLC cells (A549), was investigated. Cell‑based functional assays, real‑time RT‑qPCR and western blot assays were used. HCT116 [p53 wild‑type (WT)] and HCT116 p53‑/‑ (p53 null) were used as control cells. The results demonstrated that SCH 529074 treatment caused significant reduction in cell viability and colony formation activity in p53 mutant, p53 WT and p53‑deficient cells. The treatment of NSCLC cells with SCH 529074 resulted in a dose‑dependent induction of apoptosis and G0/G1 cell cycle arrest, which was associated with the activation of caspases (3 and 7), p53‑independent upregulation of p21 and PUMA as well as increased LC3II, a biomarker of autophagy. The combination treatment with the autophagy inhibitor chloroquine (CQ) and SCH 529074 led to decreased cell viability, colony formation and increased induction of apoptosis. The data indicated that SCH 529074 may exert its growth inhibitory function in a p53‑independent manner in NSCLC cells.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>République populaire de Chine</li></country></list><tree><country name="Allemagne"><noRegion><name sortKey="Nenkov, Miljana" sort="Nenkov, Miljana" uniqKey="Nenkov M" first="Miljana" last="Nenkov">Miljana Nenkov</name></noRegion><name sortKey="Chen, Yuan" sort="Chen, Yuan" uniqKey="Chen Y" first="Yuan" last="Chen">Yuan Chen</name><name sortKey="Haase, Daniela" sort="Haase, Daniela" uniqKey="Haase D" first="Daniela" last="Haase">Daniela Haase</name><name sortKey="Li, Yong" sort="Li, Yong" uniqKey="Li Y" first="Yong" last="Li">Yong Li</name><name sortKey="Ma, Yunxia" sort="Ma, Yunxia" uniqKey="Ma Y" first="Yunxia" last="Ma">Yunxia Ma</name><name sortKey="Petersen, Iver" sort="Petersen, Iver" uniqKey="Petersen I" first="Iver" last="Petersen">Iver Petersen</name><name sortKey="Zhou, Zhongwei" sort="Zhou, Zhongwei" uniqKey="Zhou Z" first="Zhongwei" last="Zhou">Zhongwei Zhou</name></country><country name="République populaire de Chine"><noRegion><name sortKey="Lu, Guanghua" sort="Lu, Guanghua" uniqKey="Lu G" first="Guanghua" last="Lu">Guanghua Lu</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/ChloroquineV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000146 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000146 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= ChloroquineV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= pubmed:32186773
|texte= Growth inhibitory role of the p53 activator SCH 529074 in non‑small cell lung cancer cells expressing mutant p53.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:32186773" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a ChloroquineV1
| This area was generated with Dilib version V0.6.33. |  |