Quinovic Acid Enhances the Cytotoxicity of KHYG ‐1 Cells by Modulating the Ras/ MAPK Signalling Pathway and Interferon‐Gamma Expression

ABSTRACT Quinovic acid is a key constituent of cat's claw ( Uncaria tomentosa ) extract and exhibits antioxidant and anti‐inflammatory activities. In this study, we investigated the potential of quinovic acid to enhance natural killer (NK) cell activity by using the KHYG‐1 cell line. Our data indicated that quinovic acid increased the expression levels of cytolytic molecules, including perforin, granzymes A and B, Fas ligand, and granulysin, and induced the phosphorylation of the transcription factors CREB and STAT4, thereby enhancing cytotoxic activity against K562 cells. Furthermore, when KHYG‐1 cells were cocultured with K562 cells in the presence of quinovic acid, we observed an increase in the expression of t‐Bid, cleaved caspases 3, 8, and 9, and PARP, promoting apoptosis in K562 cells. Quinovic acid also reduced the expression of SET, Ape1, and HMGB2, effectively inhibiting the DNA repair mechanism in target cells. Similar results were observed in other cancer cell lines. In addition, quinovic acid induced interferon‐gamma secretion by upregulating the Ras/MAPK and PI3K/AKT/mTOR signalling pathways through the activation of NKG2D and other NK receptors. These effects were observed not only in KHYG‐1 cells but also in NK cells derived from adult patients with head and neck squamous cell carcinoma. Our findings suggest that quinovic acid enhances NK cell cytotoxicity, showing promise as a potential therapeutic against various cancer cell types.