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Int. J. Mol. Sci. 2018, 19(10), 3243; https://doi.org/10.3390/ijms19103243

Inhibition of LINE-1 Retrotransposition by Capsaicin

Division of Virology, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
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Received: 19 September 2018 / Revised: 13 October 2018 / Accepted: 16 October 2018 / Published: 19 October 2018
(This article belongs to the Special Issue Transposable Elements)
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Abstract

Long interspersed nuclear element 1 (LINE-1 or L1) is a non-long terminal repeat (LTR) retrotransposon that constitutes approximately 17% of the human genome. Since approximately 100 copies are still competent for retrotransposition to other genomic loci, dysregulated retrotransposition of L1 is considered to be a major risk factor of endogenous mutagenesis in humans. Thus, it is important to find drugs to regulate this process. Although various chemicals are reportedly capable of affecting L1 retrotransposition, it is poorly understood whether phytochemicals modulate L1 retrotransposition. Here, we screened a library of compounds that were derived from phytochemicals for reverse transcriptase (RT) inhibition with an in vitro RT assay. We identified capsaicin as a novel RT inhibitor that also suppressed L1 retrotransposition. The inhibitory effect of capsaicin on L1 retrotransposition was mediated neither through its receptor, nor through its modulation of the L1 promoter and/or antisense promoter activity, excluding the possibility that capsaicin indirectly affected L1 retrotransposition. Collectively, capsaicin suppressed L1 retrotransposition most likely by inhibiting the RT activity of L1 ORF2p, which is the L1-encoded RT responsible for L1 retrotransposition. Given that L1-mediated mutagenesis can cause tumorigenesis, our findings suggest the potential of capsaicin for suppressing cancer development. View Full-Text
Keywords: anti-cancer; capsaicin; inhibitor; LINE-1; L1; phytochemicals; retrotransposition; reverse transcriptase anti-cancer; capsaicin; inhibitor; LINE-1; L1; phytochemicals; retrotransposition; reverse transcriptase
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Nishikawa, Y.; Nakayama, R.; Obika, S.; Ohsaki, E.; Ueda, K.; Honda, T. Inhibition of LINE-1 Retrotransposition by Capsaicin. Int. J. Mol. Sci. 2018, 19, 3243.

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