Oral cancer is the fourth leading cause of cancer-related deaths in male population in Taiwan. Despite recent advances in radiotherapy and chemotherapy, the survival of patients with oral cancer has not improved significantly. Continued investigation of new chemotherapeutic agents is thus needed.
Several studies have showed the importance of lipooxygenase (LOX) in the development of human cancer, including pancreatic, breast, prostate, and colon cancer. Recent study found 5-LOX overexpression in human oral cancer. In this study, we examined the effects of esculetin, a 5-LOX inhibitor, on cell proliferation, cell cycle and apoptosis of oral cancer cell line SAS. Esculetin significantly inhibited the proliferation of SAS oral cancer cell lines in a concentration-dependent manner. Esculetin treatment induced PARP cleavage and Caspase 3 activation. Unlike previous studies on other types of cancer cells, esculetin treatment did not change the expression of anti-apoptotic proteins Bcl-2、Bcl-x/l and Mcl-1 on SAS cells. Esculetin also did not cause cytochrome C release. However, esculetin treatment induced the expression of a death receptor, DR5. This result indicated that esculetin induced apoptosis in SAS cells via extrinsic pathway.
Flow cytometric analysis showed that esculetin treatment induced cell cycle arrest in S phase. Esculetin treatment did not change the expression of p53、cyclin A、cyclin E、CDK1 and CDK2 in oral cancer cell line SAS. Whereas, it down-regulated the expression of p21、p27、cyclin B and cyclin D. These results indicated that the anticancer effects of esculetin on oral cancer cells may be related to the S phase arrest and induction of apoptosis.