4.4 Article

A novel translation inhibitor, mersicarpine, inhibits S-phase progression and induces apoptosis in HL60 cells

Journal

BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY
Volume 85, Issue 1, Pages 92-96

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/bbb/zbaa070

Keywords

alkaloid; translation inhibitor; cell cycle arrest; apoptosis; reactive oxygen species

Funding

  1. JSPS KAKENHI [JP23102013]
  2. Platform Project for Supporting Drug Discovery and Life Science Research (Basis for Supporting Innovative Drug Discovery and Life Science Research [BINDS]) from AMED [JP20am0101099]

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Mersicarpine can reversibly arrest the cell cycle progression in S-phase and induce apoptosis in human leukemia cell line HL60. It also inhibits protein synthesis, making it a novel translation inhibitor.
Mersicarpine is an aspidosperma alkaloid isolated from the Kopsia genus of plants. Its intriguing structural features have attracted much attention in synthetic organic chemistry, but no biological activity has been reported. Here, we report the effects of mersicarpine on human leukemia cell line HL60. At concentrations above 30 mu m, mersicarpine reversibly arrested cell cycle progression in S-phase. At higher concentrations, it induced not only production of reactive oxygen species, but also apoptosis. Macromolecular synthesis assay revealed that mersicarpine specifically inhibits protein synthesis. These results suggest that mersicarpine is a novel translation inhibitor that induces apoptosis.

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