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http://dx.doi.org/10.4014/jmb.1908.08043

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)
Publication Information
Journal of Microbiology and Biotechnology / v.30, no.1, 2020 , pp. 31-37 More about this Journal
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
Nucleus condensation; plasma membrane; $Ca^{2+}$ signaling; $Ca^{2+}$ ionophore-like agent; ERK pathway;
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