Okanin Suppresses the Growth of Colorectal Cancer Cells by Targeting at Peroxiredoxin 5.

ABSTRACT: Okanin is a natural product with few known biological activities. Its anti-cancer effects and the underlying mechanisms are investigated. It is found that okanin inhibits cancer cell growth (25-50 µm) with minimal effects on non-cancerous colorectal cells except at much higher doses (i.e., > 100 µm). In colorectal HCT116 cancer cells, okanin binds directly to peroxiredoxin 5 (PRDX5) at a site opposite the catalytic domain, which directly inhibits the enzymatic activity and triggers the production of reactive oxygen species, leading to independent apoptosis and ferroptosis. The binding also causes WSB1-mediated ubiquitination degradation of PRDX5, resulting in reduced transcription and SIAH2-mediated ubiquitination degradation of GPX4, which similarly causes apoptosis and ferroptosis. In xe

SUBMITTER: Zhao JZ 

PROVIDER: S-EPMC12631902 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature