Inhibitory effects of lupeal acetate of Cortex periplocae on N-nitrosomethylbenzylamine-induced rat esophageal tumorigenesis.

Lupeal acetate of Cortex periplocae (CPLA), a triterpene compound extracted from a traditional Chinese herb, has been identified as an inhibitor of cancer cell growth. The objective of the present study was to evaluate the potential mechanisms through which CPLA inhibits N-nitrosomethylbenzylamine (NMBA)-induced rat esophageal tumorigenesis. We treated F344 rats subcutaneously with the esophageal carcinogen NMBA (0.5 mg/kg body weight) and intramuscularly with CPLA (20 mg/kg), 3 times a week for 5 weeks. Rats were then sacrificed at weeks 9, 15 or 25, esophageal tissues were collected and tumor data were recorded. To investigate the mechanisms by which CPLA modulates tumorigenesis in esophagus, we evaluated the protein expression of glycogen synthase kinase-3β (GSK-3β) and β-catenin and the gene expression of c-myc. CPLA significantly (P<0.05) reduced the incidence of esophageal tumors observed at 25 weeks from 93.3% in NMBA-treated controls to 33.3% in the NMBA- and CPLA-treated rats. CPLA reduced β-catenin and c-myc expression, but increased GSK-3β expression, in preneoplastic lesions of the esophagus. These results suggest a novel tumor-suppressive role of CPLA through the activation of GSK-3β expression and the inhibition of β-catenin and c-myc expression. Therefore, CPLA is a potential therapeutic candidate for esophageal squamous cell carcinoma.