Thiodigalactoside shows antitumour activity by beta‐galactoside‐binding protein and regulatory T cells inhibition in oral squamous cell carcinoma

Objective Thiodigalactoside ( TDG ), a synthetic inhibitor of β ‐galactoside‐binding protein (β ‐ GBP ) suppresses tumour growth by inhibiting multiple cancer enhancing activities of β ‐ GBP . Hence, we attempted to understand whether disruption of β ‐ GBP functions and indirect inhibition of T reg cells by TDG affect the growth and establishment of oral cancer cells. Method The growth, morphology, cell cycle regulation, apoptosis induction and angiogenesis of oral cancer cell lines ( SCC ‐4, SCC ‐9, SCC ‐25) via MACS ‐purified T reg cells were performed by MTT , propidium iodide ( PI ) staining, annexin‐V‐binding assay and ELISA respectively. Results Treatment with β ‐ GBP showed growth‐promoting effects on T regs and oral cancer cells. However, the treatment with its inhibitor TDG resulted in inhibition of T reg subsets and also decreased the frequency of IL 10 + and IL 35 + T regs indicating its immunomodulatory effects. Additionally, TDG treatment significantly ( P  < 0.001) inhibited the growth of OSCC cells with a concomitant induction of apoptosis, cell cycle arrest and anti‐angiogenesis. Conclusion It appears that TDG concurrently prevents many tumour‐promoting effects of β ‐ GBP in oral cancer cells possibly by T reg inhibition. This offers a preclinical proof of the concept that therapeutic targeting of β ‐ GBP can overcome T reg ‐mediated tumour promotion and immunosuppression in oral cancer patients.