Betulinic acid increases radiosensitization of oral squamous cell carcinoma through inducing Sp1 sumoylation and PTEN expression

Abstract

Radiotherapy is one of the most effective non-surgical treatments for oral squamous cell carcinoma. However, radioresistance remains a major impediment to radiotherapy. Although BetA (Betulinic acid) can induce radiosensitization, the underlying mechanism and whether it could induce radiosensitization in oral squamous cell carcinoma are not fully understood. In this study, we showed that BetA increased radiosensitization in CAL-27 and Tca-83 cells. Radiation-triggered Sp1 overexpression was responsible for radioresistance of OSCC (oral squamous cell carcinoma) cells. Treatment with BetA downregulated Sp1 and upregulated PTEN through inducing Sp1 sumoylation and correspondingly increased radiosensitization. Moreover, Sumoylation of Sp1 upregulated PTEN protein expression by downregulating Sp1 as well as inhibiting Sp1 DNA binding activity, thereby leading to the activation of PTEN transcription. Our results suggested that BetA was able to enhance radiosensitization at least partially by downregulating Sp1 and upregulating PTEN through inducing Sp1 sumoylation. BetA is suggested to be a promising drug for increasing radiosensitization in oral squamous cell carcinoma radiotherapy.