In contrast, the levels of the apoptosis-promoting proteins Bax, cleaved caspase-3 (cl-caspase 3), and cleaved-poly (ADP-ribose) polymerase (Cl-PARP) decreased in both HNSCC cell lines exposed to long-term NNK and arecoline treatment (Fig 4B). Here, CASP3 is linked to head and neck squamous cell carcinoma.