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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 Ca 2+ 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 Ca 2+ ionophore-like agent with a distinctly different chemical structure from that of previously reported Ca 2+ ionophores. These results indicate that CRM646-A has the potential to be used as a new and effective antimetastatic drug.

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