Capsaicin: A "hot" KDM1A/LSD1 inhibitor from peppers

Gang Jia; Shundong Cang; Peizhi Ma; Zhiyu Song

doi:10.1016/j.bioorg.2020.104161

Capsaicin: A "hot" KDM1A/LSD1 inhibitor from peppers

Bioorg Chem. 2020 Oct:103:104161. doi: 10.1016/j.bioorg.2020.104161. Epub 2020 Aug 21.

Authors

Gang Jia¹, Shundong Cang¹, Peizhi Ma², Zhiyu Song³

Affiliations

¹ Department of Oncology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, China.
² Department of Pharmacy, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, China.
³ Department of Pharmacy, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, China. Electronic address: song545669744@163.com.

PMID: 32889380
DOI: 10.1016/j.bioorg.2020.104161

Abstract

Capsaicinoids are plant secondary metabolites, and capsaicin is the main principal that responsible to the pungency of chili peppers, with widely application as food additive. In our study, capsaicin was characterized as lysine specific demethylase 1A (KDM1A/LSD1) inhibitor with IC₅₀ of 0.6 ± 0.0421 μM in biochemical level, and can bind KDM1A recombinant directly and reversibly. Further cellular study confirmed that capsaicin can bind and inhibit KDM1A in gastric cancer cell line BGC-823 and further inhibit cell invasion and migration by reversing epithelial-mesenchymal transition (EMT). In sum, our findings identified KDM1A as a target of capsaicin and reveals capsaicin as a modifier of histone methylation for the first time, which may provide a new skeleton for further optimization of KDM1A inhibitor.

Keywords: Capsaicin; EMT; Gastric cancer; Inhibitor; KDM1A.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Capsaicin / pharmacology
Capsaicin / therapeutic use*
Histone Demethylases / antagonists & inhibitors*
Humans
Molecular Structure
Structure-Activity Relationship

Substances

Histone Demethylases
KDM1A protein, human
Capsaicin