A high‐throughput screening assay was developed and applied to a large library of natural product extract samples, in order to identify compounds which preferentially inhibited the in vitro 2D growth of a highly metastatic osteosarcoma cell line (MG63.3) compared to a cognate parental cell line (MG63) with low metastatic potential. Evaluation of differentially active natural product extracts with bioassay‐guided fractionation led to the identification of lovastatin (IC₅₀ = 11 µm) and the limonoid toosendanin (IC₅₀ = 26 nm). Other statins and limonoids were then tested, and cerivastatin was identified as a particularly potent (IC₅₀ < 0.1 µm) and selective agent. These compounds potently and selectively induced apoptosis in MG63.3 cells, but not MG63. Assays with other cell pairs were used to examine the generality of these results. Statins and limonoids may represent unexplored opportunities for development of modulators of osteosarcoma metastasis. As cerivastatin was previously approved for clinical use, it could be considered for repurposing in osteosarcoma, pending validation in further models.

中文翻译：

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通过天然产物的高通量细胞筛选鉴定潜在的骨肉瘤转移调节剂。

开发了一种高通量筛选测定并将其应用于大型天然产物提取物样品库，以鉴定与同源亲本相比优先抑制高转移性骨肉瘤细胞系 (MG63.3) 体外二维生长的化合物具有低转移潜能的细胞系（MG63）。通过生物测定指导的分级分离评估不同活性的天然产物提取物，鉴定出洛伐他汀 (IC ₅₀  = 11 µ m ) 和柠檬苦素类川楝素 (IC ₅₀  = 26 nm )。然后测试了其他他汀类药物和柠檬苦素，并确定西立伐他汀是一种特别有效的（IC ₅₀  < 0.1 µ m) 和选择性试剂。这些化合物在 MG63.3 细胞中有效和选择性地诱导细胞凋亡，但不是 MG63。使用其他细胞对的测定来检查这些结果的普遍性。他汀类药物和柠檬苦素类药物可能代表开发骨肉瘤转移调节剂的未开发机会。由于 cerivastatin 之前已被批准用于临床，因此可以考虑将其重新用于骨肉瘤，有待进一步模型的验证。