BACKGROUND : High HOX gene expression has been described in many cancers, including oral squamous cell
carcinoma and the functional roles of these genes are gradually being understood. The pattern of overexpression
suggests that inhibition may be useful therapeutically. Inhibition of HOX protein binding to PBX cofactors by the
use of synthetic peptides, such as HXR9, results in apoptosis in multiple cancers.
METHODS : Activity of the HOX-PBX inhibiting peptide HXR9 was tested in immortalised normal oral (NOK),
potentially-malignant (PMOL) and squamous cell carcinoma (OSCC) cells, compared to the inactive peptide
CXR9. Cytotoxicity was assessed by LDH assay. Expression of PBX1/2 and c-Fos was assessed by qPCR and
western blotting. Apoptosis was assessed by Annexin-V assay.
RESULTS : PMOL and OSCC cells expressed PBX1/2. HOX-PBX inhibition by HXR9 caused death of PMOL and
OSCC cells, but not NOKs. HXR9 treatment resulted in apoptosis and increased expression of c-Fos in some
cells, whereas CXR9 did not. A correlation was observed between HOX expression and resistance to HXR9.
CONCLUSION : Inhibition of HOX-PBX interactions causes selective apoptosis of OSCC/PMOL, indicating selective
toxicity that may be useful clinically.