Curbing the Deregulation of Glycosylation in Tongue Carcinoma Cells with Natural Compounds.

ABSTRACT

BACKGROUND: Aberrant glycosylation has been recently considered as a major hallmark of cancer. Furthermore, we have reported that aberrant glycosylation, mainly sialylation and fucosylation, plays a major role in oral cancer progression and metastasis. OBJECTIVE: In the present study, we evaluated the role of tobacco compounds (4-NQO, NNK, Benzopyrene), natural compounds (Curcumin, Butein and Piceatannol) and commonly used chemotherapeutic compound (Cisplatin) on sialylation and fucosylation transcript levels in the tongue cancer cell line (SAS). METHODS: The SAS cells were treated with the tobacco compounds, natural compounds and Cisplatin after obtaining their IC50 values using MTT assay. After 24 hr treatment of the compounds, RNA was isolated from the cells and converted to cDNA. RT-qPCR was performed for mRNA expression of glycosylation transcripts. RESULTS: The treatment of tobacco compounds on the SAS cells resulted in increased mRNA levels of ST3GAL1, NEU3, FUT5 and FUT6 in a dose-dependent manner. The treatment of Curcumin and Butein resulted in lower mRNA levels of FUT8, whereas dose-dependent higher mRNA levels of FUT3 were also observed after the treatment of Curcumin. SAS cells exhibited a dose-dependent decrease in ST3GAL2, FUT5 and FUT8 mRNA after Piceatannol treatment. Furthermore, Cisplatin treatment on the SAS cells resulted in increased mRNA levels of FUT3 as the concentration increased from 100 µM to 200 µM. While, treatment of Cisplatin resulted in decreased mRNA levels of ST3GAL2, ST3GAL3, FUT5 and FUT8 in a dose-dependent manner. All together, the data revealed Piceatannol as a potent synergistic for Cisplatin to target the altered glycosylation for better treatment management of tongue carcinoma. CONCLUSION: The study provides a normal approach of targeting aberrant glycosylation with natural compounds, which may open the possibility of newer therapeutic strategies using natural compounds alone or in combination with other conventional therapies.