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

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.

Breast cancer; MKP-3; PD-L1; scoparone.