Epo-C12 inhibits peroxiredoxin 1 peroxidase activity

Tomoka Yoda; Masateru Furuta; Tomohiko Tsutsumi; Seiki Ikeda; Shunsuke Yukizawa; Satoshi Arai; Akinori Morita; Kenji Yamatoya; Kazuya Nakata; Shusuke Tomoshige; Kenji Ohgane; Yuuki Furuyama; Kengo Sakaguchi; Fumio Sugawara; Susumu Kobayashi; Masahiko Ikekita; Kouji Kuramochi

doi:10.1016/j.bmc.2021.116203

Epo-C12 inhibits peroxiredoxin 1 peroxidase activity

Bioorg Med Chem. 2021 Jul 1:41:116203. doi: 10.1016/j.bmc.2021.116203. Epub 2021 May 10.

Authors

Tomoka Yoda¹, Masateru Furuta¹, Tomohiko Tsutsumi¹, Seiki Ikeda¹, Shunsuke Yukizawa¹, Satoshi Arai¹, Akinori Morita², Kenji Yamatoya³, Kazuya Nakata⁴, Shusuke Tomoshige⁵, Kenji Ohgane¹, Yuuki Furuyama¹, Kengo Sakaguchi¹, Fumio Sugawara¹, Susumu Kobayashi⁶, Masahiko Ikekita¹, Kouji Kuramochi⁷

Affiliations

¹ Department of Applied Biological Science, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
² Department of Applied Biological Science, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan; Department of Biomedical Science and Technology, Graduate School of Biomedical Sciences, Tokushima University, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan.
³ Department of Applied Biological Science, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan; Institute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu-City, Chiba, 279-0021, Japan.
⁴ Department of Applied Biological Science, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan; Graduate School of Bio-Applications and Systems Engineering, Tokyo University of Agriculture and Technology, 2-24-16 Nakacho, Koganei, Tokyo, 184-0012, Japan.
⁵ Department of Applied Biological Science, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan; Graduate School of Life Sciences, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577, Japan.
⁶ Department of Pharmacy, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
⁷ Department of Applied Biological Science, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan. Electronic address: kuramoch@rs.tus.ac.jp.

PMID: 34015702
DOI: 10.1016/j.bmc.2021.116203

Abstract

Epo-C12 is a synthetic derivative of epolactaene, isolated from Penicillium sp. BM 1689-P. Epo-C12 induces apoptosis in human acute lymphoblastoid leukemia BALL-1 cells. In our previous studies, seven proteins that bind to Epo-C12 were identified by a combination of pull-down experiments using biotinylated Epo-C12 (Bio-Epo-C12) and mass spectrometry. In the present study, the effect of Epo-C12 on peroxiredoxin 1 (Prx 1), one of the proteins that binds to Epo-C12, was investigated. Epo-C12 inhibited Prx 1 peroxidase activity. However, it did not suppress its chaperone activity. Binding experiments between Bio-Epo-C12 and point-mutated Prx 1s suggest that Epo-C12 binds to Cys⁵² and Cys⁸³ in Prx 1. The present study revealed that Prx 1 is one of the target proteins through which Epo-C12 exerts an apoptotic effect in BALL-1 cells.

Keywords: Chaperone; Epolactaene; Peroxidase; Peroxiredoxin 1; Reactive oxygen species.

MeSH terms

Animals
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects*
Cell Line, Tumor
Enzyme Inhibitors
Epoxy Compounds / chemistry
Gene Expression Regulation, Enzymologic / drug effects
Humans
Molecular Structure
Mutation
Peroxiredoxins / antagonists & inhibitors*
Peroxiredoxins / genetics
Peroxiredoxins / metabolism
Polyenes / chemistry

Substances

Antineoplastic Agents
Enzyme Inhibitors
Epoxy Compounds
Polyenes
epolactaene
PRDX1 protein, human
Peroxiredoxins