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

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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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Acknowledgements

This study was supported by Natural Science Foundation of China (nos. 81574038 and 81673979), Shenzhen Basic Discipline Layout Project (no. JCYJ20170412161254416), Shenzhen Sanming Project of Medical and Health (No. SZSM 201612049), the Science and Technology Project of Guangdong (no. 2014A020210001), Natural Science Foundation of Guangdong Province (nos. 2018A030313393 and 2016A030313114), Scientific Research and Innovation Fund of Jinan University/the Fundamental Research Funds for the Central Universities (no. 21615464), and Science and Technology Program of Guangzhou (no. 201803010051).

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Author notes

  1. Jian Chen, Xiaofei Huang and Cheng Tao contributed equally to this work.

Authors and Affiliations

  1. Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, 510632, China

    Jian Chen, Cheng Tao, Zide Chen, Qiang Zeng & Min Ma

  2. The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen, 518035, China

    Jian Chen, Cheng Tao, Xinping Li, Qiang Zeng & Zhengzhi Wu

  3. Shenzhen Institute of Geriatrics, Shenzhen, 518020, China

    Jian Chen, Cheng Tao, Xinping Li, Qiang Zeng & Zhengzhi Wu

  4. Research Center of Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China

    Jian Chen, Xiaofei Huang & Ren Zhang

  5. Department of Cardiovascular Medicine, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, 450000, China

    Li Wang

  6. College of Traditional Chinese Medicine, Jinan University, Guangzhou, 510632, China

    Min Ma

  7. The First Affiliated Hospital of Jinan University, Guangzhou, 510630, China

    Min Ma

  8. Department of Medical Biotechnology, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China

    Ren Zhang

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  1. Jian Chen
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Chen, J., Huang, X., Tao, C. et al. Berberine chloride suppresses non-small cell lung cancer by deregulating Sin3A/TOP2B pathway in vitro and in vivo. Cancer Chemother Pharmacol 86, 151–161 (2020). https://doi.org/10.1007/s00280-020-04050-y

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