Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Jul;86(1):151-161.
doi: 10.1007/s00280-020-04050-y. Epub 2020 Jun 30.

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

Jian Chen #  1   2   3   4 , Xiaofei Huang #  4 , Cheng Tao #  1   2   3 , Li Wang  5 , Zide Chen  1 , Xinping Li  2   3 , Qiang Zeng  1   2   3 , Min Ma  6   7   8 , Ren Zhang  9   10 , Zhengzhi Wu  11   12
Affiliations

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

Jian Chen et al. Cancer Chemother Pharmacol. 2020 Jul.

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.

Keywords: Berberine; DNA damage; NSCLC; Sin3A; TOP2B.

PubMed Disclaimer

References

    1. Wakelee H, Kelly K, Edelman MJ (2014) 50 Years of progress in the systemic therapy of non-small cell lung cancer. Am Soc Clin Oncol Educ Book. https://doi.org/10.14694/EdBook_AM.2014.34.177 - DOI - PubMed - PMC
    1. Amable L (2016) Cisplatin resistance and opportunities for precision medicine. Pharmacol Res 106:27–36. https://doi.org/10.1016/j.phrs.2016.01.001 - DOI - PubMed
    1. Feng X, Liu H, Zhang Z, Gu Y, Qiu H, He Z (2017) Annexin A2 contributes to cisplatin resistance by activation of JNK-p53 pathway in non-small cell lung cancer cells. J Exp Clin Cancer Res 36(1):123. https://doi.org/10.1186/s13046-017-0594-1 - DOI - PubMed - PMC
    1. Xiao L, Lan X, Shi X, Zhao K, Wang D, Wang X, Li F, Huang H, Liu J (2017) Cytoplasmic RAP1 mediates cisplatin resistance of non-small cell lung cancer. Cell Death Dis 8(5):e2803. https://doi.org/10.1038/cddis.2017.210 - DOI - PubMed - PMC
    1. Drake FH, Zimmerman JP, McCabe FL, Bartus HF, Per SR, Sullivan DM, Ross WE, Mattern MR, Johnson RK, Crooke ST et al (1987) Purification of topoisomerase II from amsacrine-resistant P388 leukemia cells. Evidence for two forms of the enzyme. J Biol Chem 262(34):16739–16747 - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources