2020 ; Vol.30-1: 31~37
|Author||Yukihiro Asami, Sun-Ok Kim, Jun-Pil Jang, Sung-Kyun Ko, Bo Yeon Kim, Hiroyuki Osada, Jae-Hyuk Jang, Jong Seog Ahn|
|Place of duty||Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju 28116, Korea,Chemical Biology Research Group, RIKEN CSRS, Saitama 351-0198, Japan,Kitasato Institute for Life Sciences, Kitasato University, Tokyo 108-8641, Japan|
|Title||CRM646-A, a Fungal Metabolite, Induces Nucleus Condensation by Increasing Ca2+ Levels in Rat 3Y1 Fibroblast Cells|
J. Microbiol. Biotechnol.2020 ;
|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.|
|Key_word||Nucleus condensation, plasma membrane, Ca2+ signaling, Ca2+ ionophore-like agent, ERK pathway|
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