Human cathelicidin antimicrobial peptide suppresses proliferation, migration and invasion of oral carcinoma HSC-3 cells via a novel mechanism involving caspase-3 mediated apoptosis

Human cathelicidin antimicrobial peptide and its active product, LL-37 (CAMP/LL-37), exhibit a broad spectrum of antimicrobial effects. An increasing number of studies have shown that human CAMP/LL-37 also serves significant roles in various types of cancer. The primary aims of the present study were to investigate the roles and mechanisms of human CAMP/LL-37 in oral squamous cell carcinoma (OSCC) cells. The results indicated that either LL-37 C-terminal deletion mutants (CDEL) or CAMP stable expression in HSC-3 cells reduced colony formation, proliferation, migration and invasion ability of the cells. Expression analysis demonstrated that either CDEL or CAMP stable expression in HSC-3 cells induced caspase-3 mediated apoptosis via the P53-Bcl-2/BAX signalling pathway, whereas the levels of cell cycle-related proteins, cyclin B1 and PKR-like ER kinase, were significantly upregulated in the CAMP, but not in the CDEL overexpressing cells. Transcriptional profile comparisons revealed that CDEL or CAMP stable expression in HSC-3 cells upregulated expression of genes involved in the IL-17-dependent pathway compared with the control. Taken together, these results suggest that CAMP may act as a tumour suppressor in OSCC cells, and the underlying mechanism involves the induction of caspase-3 mediated apoptosis via the P53-Bcl-2/BAX signalling pathway.