title: Enoxacin inhibits growth of prostate cancer cells and effectively restores microRNA processing.
abstract: Prostate cancer (PCa) is one of the most incident malignancies worldwide. Although efficient therapy is available for early-stage PCa, treatment of advanced disease is mainly ineffective and remains a clinical challenge. microRNA (miRNA) dysregulation is associated with PCa development and progression. In fact, several studies have reported a widespread downregulation of miRNAs in PCa, which highlights the importance of studying compounds capable of restoring the global miRNA expression. The main aim of this study was to define the usefulness of enoxacin as an anti-tumoral agent in PCa, due to its ability to induce miRNA biogenesis in a TRBP-mediated manner. Using a panel of five PCa cell lines, we observed that all of them were wild type for the TARBP2 gene and expressed TRBP protein. Furthermore, primary prostate carcinomas displayed normal levels of TRBP protein. Remarkably, enoxacin was able to decrease cell viability, induce apoptosis, cause cell cycle arrest, and inhibit the invasiveness of cell lines. Enoxacin was also effective in restoring the global expression of miRNAs. This study is the first to show that PCa cells are highly responsive to the anti-tumoral effects of enoxacin. Therefore, enoxacin constitutes a promising therapeutic agent for PCa.
authors: Cancer Epigenetics Group, Research Center of the Portuguese Oncology Institute, Porto, Portugal.
authors: Elsa
authors: E
authors: Sousa
authors: Inês
authors: I
authors: Graça
authors: Tiago
authors: T
authors: Baptista
authors: Filipa Q
authors: FQ
authors: Vieira
authors: Carlos
authors: C
authors: Palmeira
authors: Rui
authors: R
authors: Henrique
authors: Carmen
authors: C
authors: Jerónimo
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D015365:Enoxacin / Q000494:pharmacology* / Q000627:therapeutic use; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D009361:Neoplasm Invasiveness; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D012323:RNA Processing, Post-Transcriptional / Q000187:drug effects / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics; D043244:Ribonuclease III / Q000378:metabolism; D000099253:Trans-Activation Responsive RNA-Binding Protein
chemical_list: D053487:DEAD-box RNA Helicases; D015365:Enoxacin; D035683:MicroRNAs; D016601:RNA-Binding Proteins; D043244:Ribonuclease III; D000099253:Trans-Activation Responsive RNA-Binding Protein; C408087:DICER1 protein, human
keywords: TRBP; enoxacin; microRNAs; prostate cancer; therapy
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