title: The reverse transcription inhibitor abacavir shows anticancer activity in prostate cancer cell lines.
abstract: BACKGROUND
  Transposable Elements (TEs) comprise nearly 45% of the entire genome and are part of sophisticated regulatory network systems that control developmental processes in normal and pathological conditions. The retroviral/retrotransposon gene machinery consists mainly of Long Interspersed Nuclear Elements (LINEs-1) and Human Endogenous Retroviruses (HERVs) that code for their own endogenous reverse transcriptase (RT). Interestingly, RT is typically expressed at high levels in cancer cells. Recent studies report that RT inhibition by non-nucleoside reverse transcriptase inhibitors (NNRTIs) induces growth arrest and cell differentiation in vitro and antagonizes growth of human tumors in animal model. In the present study we analyze the anticancer activity of Abacavir (ABC), a nucleoside reverse transcription inhibitor (NRTI), on PC3 and LNCaP prostate cancer cell lines.
  
  
  RESULTS
  ABC significantly reduces cell growth, migration and invasion processes, considerably slows S phase progression, induces senescence and cell death in prostate cancer cells. Consistent with these observations, microarray analysis on PC3 cells shows that ABC induces specific and dose-dependent changes in gene expression, involving multiple cellular pathways. Notably, by quantitative Real-Time PCR we found that LINE-1 ORF1 and ORF2 mRNA levels were significantly up-regulated by ABC treatment.
  
  
  CONCLUSIONS
  Our results demonstrate the potential of ABC as anticancer agent able to induce antiproliferative activity and trigger senescence in prostate cancer cells. Noteworthy, we show that ABC elicits up-regulation of LINE-1 expression, suggesting the involvement of these elements in the observed cellular modifications.
authors.affiliation: Department of Therapeutic Research and Drug Evaluation, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Carlini
authors.forename: Barbara
authors.initials: B
authors.lastname: Ridolfi
authors.forename: Agnese
authors.initials: A
authors.lastname: Molinari
authors.forename: Chiara
authors.initials: C
authors.lastname: Parisi
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Bozzuto
authors.forename: Laura
authors.initials: L
authors.lastname: Toccacieli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Formisano
authors.forename: Daniela
authors.initials: D
authors.lastname: De Orsi
authors.forename: Silvia
authors.initials: S
authors.lastname: Paradisi
authors.forename: Olì Maria Victoria
authors.initials: OM
authors.lastname: Grober
authors.forename: Maria
authors.initials: M
authors.lastname: Ravo
authors.forename: Alessandro
authors.initials: A
authors.lastname: Weisz
authors.forename: Romano
authors.initials: R
authors.lastname: Arcieri
authors.forename: Stefano
authors.initials: S
authors.lastname: Vella
authors.forename: Simona
authors.initials: S
authors.lastname: Gaudi
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016922:Cellular Senescence; D004251:DNA Transposable Elements; D015224:Dideoxynucleosides / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020084:Long Interspersed Nucleotide Elements; D008297:Male; D008855:Microscopy, Electron, Scanning / Q000379:methods; D020411:Oligonucleotide Array Sequence Analysis; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D012194:RNA-Directed DNA Polymerase / Q000235:genetics; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology; D000099227:Abacavir
chemical_list: D000970:Antineoplastic Agents; D004251:DNA Transposable Elements; D015224:Dideoxynucleosides; D012194:RNA-Directed DNA Polymerase; D018894:Reverse Transcriptase Inhibitors; D000099227:Abacavir