Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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CRM646-A, a Fungal Metabolite, Induces Nucleus Condensation by Increasing Ca2+ Levels in Rat 3Y1 Fibroblast Cells

  • Asami, Yukihiro (Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Kim, Sun-Ok (Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Jang, Jun-Pil (Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Ko, Sung-Kyun (Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Kim, Bo Yeon (Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Osada, Hiroyuki (Chemical Biology Research Group, RIKEN CSRS) ;
  • Jang, Jae-Hyuk (Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Ahn, Jong Seog (Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology)
  • Received : 2019.08.23
  • Accepted : 2019.11.08
  • Published : 2020.01.28
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Abstract

We previously identified a new heparinase inhibitor fungal metabolite, named CRM646-A, which showed inhibition of heparinase and telomerase activities in an in vitro enzyme assay and antimetastatic activity in a cell-based assay. In this study, we elucidated the mechanism by which CRM646-A rapidly induced nucleus condensation, plasma membrane disruption and morphological changes by increasing intracellular Ca2+ levels. Furthermore, PD98059, a mitogen-activated protein kinase (MEK) inhibitor, inhibited CRM646-A-induced nucleus condensation through ERK1/2 activation in rat 3Y1 fibroblast cells. We identified CRM646-A as a Ca2+ ionophore-like agent with a distinctly different chemical structure from that of previously reported Ca2+ ionophores. These results indicate that CRM646-A has the potential to be used as a new and effective antimetastatic drug.

Keywords

References

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