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

ObjectiveThiodigalactoside (TDG), a synthetic inhibitor of -galactoside-binding protein (-GBP) suppresses tumour growth by inhibiting multiple cancer enhancing activities of -GBP. Hence, we attempted to understand whether disruption of -GBP functions and indirect inhibition of T-reg cells by TDG affect the growth and establishment of oral cancer cells. MethodThe 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. ResultsTreatment with -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 IL10(+) and IL35(+) 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. ConclusionIt appears that TDG concurrently prevents many tumour-promoting effects of -GBP in oral cancer cells possibly by T-reg inhibition. This offers a preclinical proof of the concept that therapeutic targeting of -GBP can overcome T-reg-mediated tumour promotion and immunosuppression in oral cancer patients.