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

Creative Commons License

Karakuş F., Köstekci S., Kuzu B., Tülüce Y.

International Journal of Secondary Metabolite, cilt.13, sa.3, ss.804-816, 2026 (Scopus, TRDizin)

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 13 Sayı: 3
  • Basım Tarihi: 2026
  • Doi Numarası: 10.21448/ijsm.1863503
  • Dergi Adı: International Journal of Secondary Metabolite
  • Derginin Tarandığı İndeksler: Scopus, Central & Eastern European Academic Source (CEEAS), Directory of Open Access Journals, TR DİZİN (ULAKBİM)
  • Sayfa Sayıları: ss.804-816
  • Anahtar Kelimeler: Breast cancer, MCF-7, PD-L1, Quinine, STAT3
  • Açık Arşiv Koleksiyonu: AVESİS Açık Erişim Koleksiyonu
  • Van Yüzüncü Yıl Üniversitesi Adresli: Evet

Özet

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.