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.

PRINCIPAL FINDINGS:

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: Francesca Carlini, Barbara Ridolfi, Agnese Molinari, Chiara Parisi, Giuseppina Bozzuto, Laura Toccacieli, Giuseppe Formisano, Daniela De Orsi, Silvia Paradisi, Olì Maria Victoria Grober, Maria Ravo, Alessandro Weisz, Romano Arcieri, Stefano Vella, Simona Gaudi
• Journal: PloS one (PLoS One) Vol. 5 Issue 12 Pg. e14221 (Dec 03 2010) ISSN: 1932-6203 [Electronic] United States
• PMID: 21151977 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• DNA Transposable Elements
• Dideoxynucleosides
• Reverse Transcriptase Inhibitors
• RNA-Directed DNA Polymerase
• abacavir

Topics

• Antineoplastic Agents (pharmacology)
• Cell Line, Tumor
• Cell Proliferation
• Cellular Senescence
• DNA Transposable Elements
• Dideoxynucleosides (pharmacology)
• Drug Screening Assays, Antitumor
• Humans
• Long Interspersed Nucleotide Elements
• Male
• Microscopy, Electron, Scanning (methods)
• Oligonucleotide Array Sequence Analysis
• Prostatic Neoplasms (drug therapy)
• RNA-Directed DNA Polymerase (genetics)
• Reverse Transcriptase Inhibitors (pharmacology)