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01-07-2020 | NSCLC | Original Article

Berberine chloride suppresses non-small cell lung cancer by deregulating Sin3A/TOP2B pathway in vitro and in vivo

Authors: Jian Chen, Xiaofei Huang, Cheng Tao, Li Wang, Zide Chen, Xinping Li, Qiang Zeng, Min Ma, Ren Zhang, Zhengzhi Wu

Published in: Cancer Chemotherapy and Pharmacology | Issue 1/2020

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.

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Title: Berberine chloride suppresses non-small cell lung cancer by deregulating Sin3A/TOP2B pathway in vitro and in vivo
Authors: Jian Chen
Xiaofei Huang
Cheng Tao
Li Wang
Zide Chen
Xinping Li
Qiang Zeng
Min Ma
Ren Zhang
Zhengzhi Wu
Publication date: 01-07-2020
Publisher: Springer Berlin Heidelberg
Keywords: NSCLC
NSCLC
Published in: Cancer Chemotherapy and Pharmacology / Issue 1/2020
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-020-04050-y

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