Inhibition of LINE-1 retrotransposition by capsaicin

Yuki Nishikawa, Ryota Nakayama, Shunsuke Obika, Eriko Ohsaki, Keiji Ueda, Tomoyuki Honda

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

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.

Original languageEnglish
Article number3243
JournalInternational journal of molecular sciences
Volume19
Issue number10
DOIs
Publication statusPublished - Oct 19 2018
Externally publishedYes

Keywords

  • Anti-cancer
  • Capsaicin
  • Inhibitor
  • L1
  • LINE-1
  • Phytochemicals
  • Retrotransposition
  • Reverse transcriptase

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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