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

Author:

Shiobara Tomoko1,Nagumo Yoko23ORCID,Nakajima Rie4,Fukuyama Tohru5,Yokoshima Satoshi5,Usui Takeo26

Affiliation:

1. Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Japan

2. Faculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Japan

3. Alliance for Research on the Mediterranean and North Africa (ARENA), University of Tsukuba, Tsukuba, Japan

4. Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan

5. Graduate School of Pharmaceutical Sciences, Nagoya University, Nagoya, Japan

6. Microbiology Research Center for Sustainability (MiCS), University of Tsukuba, Tsukuba, Japan

Abstract

Abstract 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 µm, 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.

Funder

Japan Society for the Promotion of Science

AMED

Publisher

Oxford University Press (OUP)

Subject

Organic Chemistry,Molecular Biology,Applied Microbiology and Biotechnology,General Medicine,Biochemistry,Analytical Chemistry,Biotechnology

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