Fucoidan Enhances Cisplatin-induced Effects on SCC-25 Human Oral Cancer Cells by Inhibiting the PI3K/AKT Pathway

Abstract

Background/aim: Cisplatin is a drug for treating oral cancer. However, several previous studies indicate that oral cancer cells can develop resistance to cisplatin, which may result in a poor prognosis for patients with oral cancer. Fucoidan, a natural health product extracted from brown seaweed, has anticancer abilities against various types of cancer cell. This study evaluated whether fucoidan can enhance the sensitivity of oral cancer cells to cisplatin and explored the underlying mechanism.

Materials and methods: SCC-25 cells were used in the present study and treated with 0.3125 mg/ml fucoidan, 12.5 μg/ml cisplatin, or 0.3125 mg/ml fucoidan plus 12.5 μg/ml cisplatin for 48 h, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, enzyme-linked immunosorbent, and immunoblotting assays were performed to evaluate cell survival, cytokeratin-18 fragment release, and expression of markers of apoptosis and autophagy, respectively.

Results: Cotreatment with fucoidan enhanced cisplatin-induced reduction of SCC-25 cell survival compared to cisplatin alone. In addition, cotreatment also increased the expression of apoptosis markers, including activated caspase-8, activated caspase-9, activated caspase-3, and cleaved poly(ADP-ribose) polymerase (PARP), but did not increase the expression of the two autophagy markers studied, beclin and autophagy-related 12-autophagy-related 5 conjugate. Fucoidan significantly inhibited cisplatin-induced AKT serine/threonine kinase 1 activation, which promoted PARP cleavage, caspase-3 activation, and cytokeratin-18 fragment expression in SCC-25 cells.

Conclusion: Fucoidan promoted cisplatin-induced effects by inhibiting phosphatidylinositol 4,5 bisphosphate 3 kinase/AKT serine/threonine kinase 1 activation induced by cisplatin. The results of this study may provide a basis for the possible application of the combination of fucoidan and cisplatin in the clinical treatment of oral cancer in the future to improve the prognosis of patients with oral cancer.

Keywords: Fucoidan; apoptosis; cisplatin; oral cancer.