2. Academic Validation
  3. Synthesis of a novel fluorescent berberine derivative convenient for its subcellular localization study

Synthesis of a novel fluorescent berberine derivative convenient for its subcellular localization study

  • Bioorg Chem. 2020 Aug;101:104021. doi: 10.1016/j.bioorg.2020.104021.
Meng Jin 1,  Xiuna Ji 1,  Rostyslav Stoika 2,  Kechun Liu 1,  Lizhen Wang 3,  Yang Song 4
Affiliations

Affiliations

  • 1 Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250353, Shandong Province, China; Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250353, Shandong Province, China.
  • 2 Department of Regulation of Cell Proliferation and Apoptosis, Institute of Cell Biology, National Academy of Sciences of Ukraine, Lviv, Ukraine.
  • 3 Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250353, Shandong Province, China; Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250353, Shandong Province, China. Electronic address: wlzh1106@126.com.
  • 4 Biological Engineering College, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250056, Shandong Province, China.
PMID: 32629278 DOI: 10.1016/j.bioorg.2020.104021
Abstract

Berberine is a naturally occurred isoquinoline alkaloid that shows great potential for developing Anticancer drugs. However, the problem stays of poor understanding of the mechanisms of Anticancer action of berberine. It depends on evaluation of berberine's pharmacokinetics, namely monitoring of its uptake and distribution in cells, tissues and organs. In order to address these problems, we have designed and synthesized a novel berberine derivative BBR-BODIPY bearing a fluorescent tag that allows screening its interaction with the targeted cells. It was shown that the synthesized fluorescent derivative could penetrate into human breast carcinoma MCF7 cells, and then induced Apoptosis detected by the Western Blot analysis as changed expression of apoptosis-related proteins, including Bax, Bcl2, and Cyto C released from mitochondria, Cleaved Caspase 9, Cleaved PARP, Pro-Caspase 3, and Cleaved Caspase 3. The results of MitoTracker analysis followed by the confocal microscopy of sub-cellular localization of BBR-BODIPY in the MCF7 cells demonstrated excellent cell-penetrating ability of this compound even at low concentrations, and mitochondria was the main site of its accumulation. Together with the results of Western Blot analysis, these data indicated that the mitochondria pathway might be involved in berberine-induced Apoptosis.

Keywords

Anticancer; Berberine; Fluorescent probe; Fluorescently labeled natural product.

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