Advances in pharmacy and medicine have led to the development of many anti-cancer and molecular targeted agents; however, there are few agents capable of suppressing metastasis. To prevent cancer recurrence, it is essential to develop novel agents for inhibiting metastasis. Coumarin-based compounds have multiple pharmacological activities including anti-cancer effects. We screened a compound library constructed at Kyoto Pharmaceutical University and showed that 7,8-dihydroxy-3-(4′-hydroxyphenyl)coumarin (DHC) inhibited invasion and migration of LM8 mouse osteosarcoma cells and 143B human osteosarcoma cells in a concentration-dependent manner. DHC decreased intracellular actin filament formation by downregulating Rho small GTP-binding proteins such as RHOA, RAC1, and CDC42, which regulate actin reorganization. However, DHC did not downregulate the corresponding mRNA transcripts, whereas it downregulated Rho small GTP-binding proteins in the presence of cycloheximide, suggesting that DHC enhances the degradation of these proteins. DHC treatment inhibited metastasis and prolonged overall survival in a spontaneous metastasis mouse model. These results indicate that DHC has the potential to suppress metastasis of osteosarcoma cells by downregulating Rho small GTP-binding proteins.

药学和医学的进步导致了许多抗癌和分子靶向药物的开发；然而，很少有药物能够抑制转移。为了防止癌症复发，开发抑制转移的新型药物至关重要。基于香豆素的化合物具有多种药理活性，包括抗癌作用。我们筛选了京都药科大学构建的化合物库，结果表明 7,8-二羟基-3-(4'-羟基苯基) 香豆素 (DHC) 以浓度依赖性方式抑制 LM8 小鼠骨肉瘤细胞和 143B 人骨肉瘤细胞的侵袭和迁移方式。DHC 通过下调调节肌动蛋白重组的 Rho 小 GTP 结合蛋白（如 RHOA、RAC1 和 CDC42）来减少细胞内肌动蛋白丝的形成。然而，DHC 没有下调相应的 mRNA 转录本，而它在放线菌酮存在的情况下下调 Rho 小 GTP 结合蛋白，表明 DHC 增强了这些蛋白质的降解。在自发转移小鼠模型中，DHC 治疗可抑制转移并延长总生存期。这些结果表明 DHC 具有通过下调 Rho 小 GTP 结合蛋白来抑制骨肉瘤细胞转移的潜力。