Quinine modulates PD-L1 and STAT3 in MCF-7 cells: An in silico and in vitro study

Abstract

Programmed death-ligand 1 (PD-L1) overexpression in cancer cells is linked to immune escape and tumor progression, with signal transducer and activator of transcription 3 (STAT3) as a key transcription factor regulating its expression. This study evaluates the potential of quinine (QN), traditionally used for malaria, to target PD-L1 and STAT3 in MCF-7 breast cancer cells. The binding affinities of QN to PD-L1 and STAT3 were assessed using molecular docking. The effects of QN on PD-L1 and STAT3 gene expression were assessed via real-time polymerase chain reaction. Cell viability, migration, and colony formation were evaluated using cell culture methods, and the protein levels of vascular endothelial cell growth factor (VEGF), tubulointerstitial nephritis antigen-like 1 (TINAGL-1), and epithelial cadherin (E-cadherin) were examined via Enzyme-linked immunosorbent assay (ELISA). QN exhibited selective cytotoxicity toward MCF-7 cells (IC50: 31.7 µM) while sparing healthy HME1 mammary epithelial cells. QN treatment led to a dose-dependent decrease in PD-L1 and STAT3 gene expression in MCF-7 cells. Migration and colony formation of MCF-7 cells were significantly inhibited at 30 µM QN, whereas HME1 cell migration was unaffected, indicating a selective reduction in cancer cell motility. ELISA results revealed statistically significant VEGF downregulation and TINAGL-1 upregulation in MCF-7 cells. These findings indicate that QN suppresses MCF-7 cell growth and migration by downregulating PD-L1 and STAT3 gene expression, reducing VEGF levels, and increasing TINAGL-1 levels, highlighting the compound’s potential for PD-L1 inhibition in cancer.

Keywords

• Kinin
• PD-L1
• STAT3
• Meme kanseri
• MCF-7

Supporting Institution

The Scientific and Technological Research Council of Türkiye

Project Number

123S880

Thanks

This study was supported by Scientific and Technological Research Council of Türkiye (TUBITAK) under Grant (123S880). The authors thank to TUBITAK for their supports.

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