One cost-effective way for identifying novel cancer therapeutics is in the repositioning of available drugs for which current therapies are inadequate. Levofloxacin prevents DNA duplication in bacteria by inhibiting the activity of DNA helicase. As eukaryotic cells have similar intracellular biologic characteristics as prokaryotic cells, we speculate that antibiotics inhibiting DNA duplication in bacteria may also affect the survival of cancer cells. Here we report that levofloxacin significantly inhibited the proliferation and clone formation of cancer cells and xenograft tumor growth through cell cycle arrest at G2/M and by enhancing apoptosis. Levofloxacin significantly altered gene expression in a direction favoring anticancer activity. THBS1 and LAPTM5 were dose-dependently upregulated whereas SRD5A3, MFAP5 and P4HA1 were downregulated. Pathway analysis revealed that levofloxacin significantly regulated canonical oncogenic pathways. Specific network enrichment included a MAPK/apoptosis/cytokine-cytokine receptor interaction pathway network that associates with cell growth, differentiation, cell death, angiogenesis and development and repair processes and a bladder cancer/P53 signaling pathway network mediating the inhibition of angiogenesis and metastasis. THBS1 overlapped in 16 of the 22 enriched apoptotic pathways and the 2 pathways in the bladder cancer/P53 signaling pathway network. P4HA1 enriched in 7 of the top 10 molecular functions regulated by differential downregulated genes. Our results indicate that levofloxacin has broad-spectrum anticancer activity with the potential to benefit cancer patients already treated or requiring prophylaxis for an infectious syndrome. The efficacy we find with levofloxacin may provide insight into the discovery and the design of novel less toxic anticancer drugs.

中文翻译：

---

Levofloxacin 通过调节 THBS1、LAPTM5、SRD5A3、MFAP5 和 P4HA1 发挥广谱抗癌活性。

识别新型癌症疗法的一种经济有效的方法是重新定位现有疗法不足的可用药物。左氧氟沙星通过抑制 DNA 解旋酶的活性来防止细菌中的 DNA 复制。由于真核细胞与原核细胞具有相似的细胞内生物学特性，我们推测抑制细菌DNA复制的抗生素也可能影响癌细胞的存活。在这里，我们报告左氧氟沙星通过细胞周期阻滞在 G2/M 和增强细胞凋亡，显着抑制癌细胞的增殖和克隆形成以及异种移植肿瘤的生长。左氧氟沙星显着改变基因表达，使其朝着有利于抗癌活性的方向发展。THBS1 和 LAPTM5 呈剂量依赖性上调，而 SRD5A3、MFAP5 和 P4HA1 则下调。通路分析表明，左氧氟沙星显着调节典型的致癌通路。具体的网络富集包括与细胞生长、分化、细胞死亡、血管生成以及发育和修复过程相关的 MAPK/细胞凋亡/细胞因子-细胞因子受体相互作用通路网络，以及介导血管生成和转移抑制的膀胱癌/P53信号通路网络。THBS1 在 22 条富集的细胞凋亡通路中的 16 条以及膀胱癌/P53 信号通路网络中的 2 条通路中重叠。P4HA1 富含受差异下调基因调节的前 10 个分子功能中的 7 个。我们的结果表明，左氧氟沙星具有广谱抗癌活性，有可能使已经接受治疗或需要预防感染综合征的癌症患者受益。我们发现的左氧氟沙星的功效可能有助于深入了解新型低毒抗癌药物的发现和设计。