4-Hexylresorcinol inhibits transglutaminase-2 activity and has synergistic effects along with cisplatin in KB cells.

Resistance to chemotherapy is very important in the prognosis of tumors. Transglutaminase-2 (TG-2) mediated chemotherapy resistance has been widely reported. The objective of this study was to demonstrate the effect of 4-hexylresorcinol (4-HR) on TG-2 activity in nasopharyngeal squamous cell carcinoma cells (KB cells). Treatment with a mixture of 4-HR and cisplatin significantly decreased KB cell viability compared to treatment by cisplatin alone at 10 µg/ml (p<0.001). 4-HR inhibited TG-2 activity compared to cisplatin alone at 5, 10 and 20 µg/ml (p = 0.001, 0.001 and 0.003, respectively). Nuclear translocation of TG-2 was also inhibited by 4-HR treatment. 4-HR treatment also increased the fluorescence life-time of DAPI significantly compared to the untreated control or the cisplatin treated group (p<0.001). In conclusion, 4-HR inhibited TG-2 activity and showed a synergistic effect on tumor cell growth inhibition with cisplatin.