Degalactotigonin Inhibits Invasion and Induce Apoptosis by Targeting TGF‑β Signalling in Oral Cancer Cells

Abstract

Objectives: The study aimed to investigate the anti‑invasion and apoptotic induction effect of DGT in oral squamous cell carcinoma (OSCC) cells through inhibiting non‑canonical TGF‑β signalling.Materials and Methods: Human oral cancer KB (KERATIN-forming tumor cell line HeLa) cells were chosen to study the anti‑cancer activity of DGT in vitro experiments. The cytotoxic effect of DGT was evaluated by MTT (3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assay. Cell growth, DNA damage, invasion inhibition and apoptosis activation were evaluated by mitochondrial membrane potential (ΔΨM), comet assay, reactive oxygen species (ROS) and AO/EtBr staining. The DGT effect on protein expression levels related to invasion, apoptotic markers and its activation signalling pathways on KB cells were examined by western blotting.Results: We found that DGT antioxidant properties reduced cell viability, generates ROS, enhanced DNA damage, and MMP dissipation. Further, TGF‑β inhibitions resulted in a reduction of extracellular signal‑regulated kinase (ERK), NF‑κB and activation of JNK, p38 which increase ROS in a cancer cell that downregulates cyclin‑D1, PCNA, MMP‑2, MMP‑9, Bcl‑2 and increases Bax, Caspase‑9, Caspase‑3 protein expressions that simultaneously subdues the cancer developments.Conclusion: These findings suggest that DGT inhibiting TGF‑β mediated ERK, NF‑κB and activation of JNK, p38 caused tumour cell death via ROS stimulation and apoptosis.

Keywords: Degalactotigonin; ERK; invasion and apoptosis; NF‑κB; oral cancer; TGF‑β