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CRM646-A, a Fungal Metabolite, Induces Nucleus Condensation by Increasing Ca2+ Levels in Rat 3Y1 Fibroblast Cells

Journal of Microbiology and Biotechnology 2020년 30권 1호 p.31 ~ 37
 ( Asami Yukihiro ) - Korea Research Institute of Bioscience and Biotechnology Anticancer Agent Research Center

김선옥 ( Kim Sun-Ok ) - Korea Research Institute of Bioscience and Biotechnology Anticancer Agent Research Center
장준필 ( Jang Jun-Pil ) - Korea Research Institute of Bioscience and Biotechnology Anticancer Agent Research Center
 ( Ko Sung-Kyun ) - Korea Research Institute of Bioscience and Biotechnology Natural Medicine Research Center
김보연 ( Kim Bo-Yeon ) - Korea Research Institute of Bioscience and Biotechnology Anticancer Agent Research Center
 ( Osada Hiroyuki ) - RIKEN Center for Sustainable Research Science Chemical Biology Research Group
장재혁 ( Jang Jae-Hyuk ) - Korea Research Institute of Bioscience and Biotechnology Natural Medicine Research Center
안종석 ( Ahn Jong-Seog ) - Korea Research Institute of Bioscience and Biotechnology Anticancer Agent Research Center

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.

키워드

Nucleus condensation; plasma membrane; Ca2+ signaling; Ca2+ ionophore-like agent; ERK pathway
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