Berberine chloride suppresses non-small cell lung cancer by deregulating Sin3A/TOP2B pathway in vitro and in vivo.
Cancer Chemother Pharmacol
; 86(1): 151-161, 2020 07.
Article
em En
| MEDLINE
| ID: mdl-32607786
ABSTRACT
PURPOSE:
Berberine chloride (BBC) is a well-known plant isoquinoline alkaloid derived from Berberis aristata. In this study, we aim to explore the effect of BBC on non-small cell lung cancer (NSCLC), and further expound the underlying mechanism of BBC induces NSCLC cell death in vitro and in vivo.METHODS:
CCK-8 assay and colony formation assay were used to test the viability and colony formation ability of NSCLC cells. Apoptosis analysis was used to analyze the apoptotic cells. siRNAs were utilized to disturb the expression of Sin3A. qPCR and Western blot analysis were employed to determine mRNA and protein levels of related genes and proteins. Tumor xenografts model was used for in vivo detection.RESULTS:
BBC inhibited the proliferation and colony formation of human NSCLC cells in a dose- and time-dependent manner. In addition, BBC induced DNA double-stranded breaks (DSBs) through downregulating TOP2B level, leading to apoptosis in human NSCLC cells. The Chip-seq data of A549 cells obtained from the ENCODE consortium indicate that Sin3A binds on the promoters of TOP2B. Knockdown of Sin3A led to downregulation of TOP2B in human NSCLC cells. Furthermore, BBC decreased Sin3A expression and shortened the half-life of Sin3A, results in downregulation of TOP2B in human NSCLC cells.CONCLUSION:
In this study, we demonstrated a new mechanism that BBC suppresses human NSCLC by deregulating Sin3A/TOP2B pathway, leading to DNA damage and apoptosis in human NSCLC in vitro and in vivo.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Berberina
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Carcinoma Pulmonar de Células não Pequenas
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DNA Topoisomerases Tipo II
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Complexo Correpressor Histona Desacetilase e Sin3
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Proteínas de Ligação a Poli-ADP-Ribose
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Neoplasias Pulmonares
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article