5,7,4'-Trimethoxyflavone triggers cancer cell PD-L1 ubiquitin-proteasome degradation and facilitates antitumor immunity by targeting HRD1.
MedComm (2020)
; 5(7): e611, 2024 Jul.
Article
em En
| MEDLINE
| ID: mdl-38938284
ABSTRACT
Targeting the programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) pathway has been identified as a successful approach for tumor immunotherapy. Here, we identified that the small molecule 5,7,4'-trimethoxyflavone (TF) from Kaempferia parviflora Wall reduces PD-L1 expression in colorectal cancer cells and enhances the killing of tumor cells by T cells. Mechanistically, TF targets and stabilizes the ubiquitin ligase HMG-CoA reductase degradation protein 1 (HRD1), thereby increasing the ubiquitination of PD-L1 and promoting its degradation through the proteasome pathway. In mouse MC38 xenograft tumors, TF can activate tumor-infiltrating T-cell immunity and reduce the immunosuppressive infiltration of myeloid-derived suppressor cells and regulatory T cells, thus exerting antitumor effects. Moreover, TF synergistically exerts antitumor immunity with CTLA-4 antibody. This study provides new insights into the antitumor mechanism of TF and suggests that it may be a promising small molecule immune checkpoint modulator for cancer therapy.
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Coleções:
01-internacional
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MEDLINE
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article