Tetrahydrocurcumin targets TRIP13 inhibiting the interaction of TRIP13/USP7/c-FLIP to mediate c-FLIP ubiquitination in triple-negative breast cancer.

ABSTRACT:

Introduction

Triple-negative breast cancer (TNBC) has a high mortality rate and limited treatment options. Tetrahydrocurcumin (THC), a major metabolite of curcumin, has potential antitumor activities. However, the antitumor effects and mechanism of THC in TNBC remain elusive.

Objectives

To investigate the mechanism of THC in combating TNBC by targeting TRIP13 to disrupt the interaction of the TRIP13/USP7/c-FLIP complex and mediate c-FLIP ubiquitination both in vitro and in vivo.

Methods

Apoptosis was measured by TUNEL and flow cytometry. Click chemistry-based target fishing, CETSA, DARTS, and SPR were used to identify direct target of THC. Protein interactions was examined using co-immunoprecipitation. The role of USP7 in THC-mediated c-FLIP ubiquitination was evaluat

SUBMITTER: Sun YJ 

PROVIDER: S-EPMC12789769 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature