We have previously reported that daptomycin (DAP), a last resort antibiotic, binds to ribosomal protein S19 (RPS19) in humans and exhibits selective anti-cancer activity against MCF7 breast cancer cells. Here, we investigated the role of RPS19 in the anti-cancer effects of DAP and have found that DAP does not induce autophagy, apoptosis or cell viability but does reduce cell proliferation. Our results suggest that an extraribosomal function of RPS19 involves the regulation of vascular endothelial growth factor (VEGF) but not EGF, PDGF or FGF. Engagement of RPS19 by DAP was shown by CETSA and ITDRF_CETSA assays, and knocking down of RPS19 with siRNA increased the potency of DAP in MCF7 cells. In addition, DAP suppressed the secretion of VEGF in cancer cells and thereby inhibited cell migration. Collectively, these data provide an outline of the underlying mechanism of how DAP exhibits anti-cancer activity and suggests that RPS19 could be a promising target for the development of new anticancer drugs.

我们之前曾报道，达托霉素 (DAP) 是一种不得已的抗生素，可与人类的核糖体蛋白 S19 (RPS19) 结合，并对 MCF7 乳腺癌细胞表现出选择性抗癌活性。在这里，我们研究了 RPS19 在 DAP 抗癌作用中的作用，发现 DAP 不会诱导自噬、细胞凋亡或细胞活力，但会减少细胞增殖。我们的结果表明，RPS19 的核糖体外功能涉及血管内皮生长因子 (VEGF) 的调节，但不涉及 EGF、PDGF 或 FGF。CETSA 和 ITDRF _{CETSA显示了 DAP 对 RPS19 的参与}化验，并用 siRNA 敲低 RPS19 增加了 DAP 在 MCF7 细胞中的效力。此外，DAP抑制癌细胞中VEGF的分泌，从而抑制细胞迁移。总的来说，这些数据概述了 DAP 如何表现出抗癌活性的潜在机制，并表明 RPS19 可能是开发新抗癌药物的有前途的目标。