title: Thiodigalactoside shows antitumour activity by beta-galactoside-binding protein and regulatory T cells inhibition in oral squamous cell carcinoma.
abstract: 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 Treg cells by TDG affect the growth and establishment of oral cancer cells.
  
  
  METHODS
  The growth, morphology, cell cycle regulation, apoptosis induction and angiogenesis of oral cancer cell lines (SCC-4, SCC-9, SCC-25) via MACS-purified Treg 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 Tregs and oral cancer cells. However, the treatment with its inhibitor TDG resulted in inhibition of Treg subsets and also decreased the frequency of IL10(+) and IL35(+) Tregs 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.
  
  
  CONCLUSIONS
  It appears that TDG concurrently prevents many tumour-promoting effects of β-GBP in oral cancer cells possibly by Treg inhibition. This offers a preclinical proof of the concept that therapeutic targeting of β-GBP can overcome Treg -mediated tumour promotion and immunosuppression in oral cancer patients.
authors.affiliation: Department of Biotechnology, All India Institute of Medical Sciences (AIIMS), New Delhi, India.
authors.forename: S
authors.initials: S
authors.lastname: Aggarwal
authors.affiliation: Department of Biotechnology, All India Institute of Medical Sciences (AIIMS), New Delhi, India.
authors.forename: S N
authors.identifier: http://orcid.org/0000-0002-1659-2499
authors.initials: SN
authors.lastname: Das
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D037161:Galectins / Q000494:pharmacology*; D006258:Head and Neck Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology; D007378:Interleukins / Q000276:immunology; D009062:Mouth Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D000077195:Squamous Cell Carcinoma of Head and Neck; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D013862:Thiogalactosides / Q000494:pharmacology*
chemical_list: D043925:Angiogenesis Inducing Agents; D037161:Galectins; C508609:IL10 protein, human; D007378:Interleukins; D013862:Thiogalactosides; C532417:interleukin-35, human; D016753:Interleukin-10; C031803:thiodigalactoside
keywords: angiogenesis; beta-galactoside-binding protein; cell cycle; oral cancer; regulatory T cells; thiodigalactoside