Scoparone attenuates PD-L1 expression in human breast cancer cells by MKP-3 upregulation

Autor: Seung-Woo Kim, Chan Woo Kim, Hong Seok Kim
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Animal Cells and Systems, Vol 28, Iss 1, Pp 55-65 (2024)
Druh dokumentu: article
ISSN: 19768354
2151-2485
1976-8354
DOI: 10.1080/19768354.2024.2315950
Popis: Breast cancer is a frequently occurring malignant tumor that is one of the leading causes of cancer-related deaths in women worldwide. Monoclonal antibodies that block programed cell death 1 (PD-1)/programed cell death ligand 1 (PD-L1) – a typical immune checkpoint – are currently the recommended standard therapies for many advanced and metastatic tumors such as triple-negative breast cancer. However, some patients develop drug resistance, leading to unfavorable treatment outcomes. Therefore, other approaches are required for anticancer treatments, such as downregulation of PD-L1 expression and promotion of degradation of PD-L1. Scoparone (SCO) is a bioactive compound isolated from Artemisia capillaris that exhibits antitumor activity. However, the effect of SCO on PD-L1 expression in cancer has not been confirmed yet. This study aimed to evaluate the role of SCO in PD-L1 expression in breast cancer cells in vitro. Our results show that SCO downregulated PD-L1 expression in a dose-dependent manner, via AKT inhibition. Interestingly, SCO treatment did not alter PTEN expression, but increased the expression of mitogen-activated protein kinase phosphatase-3 (MKP-3). In addition, the SCO-induced decrease in PD-L1 expression was reversed by siRNA-mediated MKP-3 knockdown. Collectively, these findings suggest that SCO inhibited the expression of PD-L1 in breast cancer cells by upregulating MKP-3 expression. Therefore, SCO may serve as an innovative combinatorial agent for cancer immunotherapy.
Databáze: Directory of Open Access Journals
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