DNA methylation directly downregulates human cathelicidin antimicrobial peptide gene (CAMP) promoter activity.

LL-37, the active product of human cathelicidin antimicrobial peptide (CAMP) has a broad spectrum of antibacterial activity. LL-37 also has important physiological functions in immune regulation, angiogenesis and in modulating apoptosis. The roles of LL-37 in oral squamous cell carcinoma (OSCC) are still not clear. The correlation between DNA methylation and human CAMP expression is also unknown. Here human CAMP/LL-37 expression was assessed by immunohistochemistry in normal and OSCC tissues. The results indicated that low expression of CAMP/LL-37 correlated with histological differentiation and lymph node metastasis and also promoted tumor progression. A cell-specific methylation pattern in the promoter region of human CAMP was detected. Treatment with 5-aza-2'-deoxycytidine, a DNA demethylation reagent can increase human CAMP expression in epithelial cancer cells. The reporter assay showed that unmethylated human CAMP promoter activity was significantly higher than methylated promoter activity. Taken together, these results suggested that human CAMP/LL-37 might act as a tumor-suppressor in OSCC and DNA methylation might play roles during carcinogenesis via directly downregulating human CAMP promoter activity.

Inhibiting reactive oxygen species-dependent autophagy enhanced baicalein-induced apoptosis in oral squamous cell carcinoma.

Autophagy modulation has been considered a potential therapeutic strategy for oral squamous cell carcinoma (OSCC). A previous study confirmed that baicalein might possess significant anti-carcinogenic activity. However, whether baicalein induces autophagy and its role in cell death in OSCC are still unclear. The aim of this study was to investigate the anticancer activity and molecular targets of baicalein in OSCC in vitro. In this study, we found that baicalein induced significant apoptosis in OSCC cells Cal27. In addition to showing apoptosis induction, we also demonstrated baicalein-induced autophagic response in Cal27 cells. Moreover, pharmacologically or genetically blocking autophagy enhanced baicalein-induced apoptosis, indicating the cytoprotective role of autophagy in baicalein-treated Cal27 cells. Importantly, we found that baicalein triggered reactive oxygen species (ROS) generation in Cal27 cells. Furthermore, N-acetyl-cysteine, a ROS scavenger, abrogated the effects of baicalein on ROS-dependent autophagy. Therefore, we found that baicalein increased autophagy through the promotion of ROS signaling pathways in OSCC. These data also suggest that a strategy of blocking ROS-dependent autophagy to enhance the activity of baicalein warrants further attention for the treatment of OSCC.