Gelsemine induces apoptosis through a reactive oxygen species- and MAPK/JNK1/2-coregulated pathway in tongue squamous cell carcinoma cells.

Tongue cancer is recognized globally as a prevalent oral cancer, with squamous cell carcinoma accounting for over 90% of oral cancer diagnoses. Tongue squamous cell carcinoma (SCC) has a poor survival rate and is highly invasive. The present study aimed to investigate the effect of the therapeutic agent gelsemine on SAS cells line derived from tongue squamous. Gelsemine was found to induce significant cell shrinkage and morphological changes. In addition, gelsemine significantly increased apoptosis, cytotoxicity and expression of signaling proteins related to apoptosis, namely cleaved PARP and caspase-3/-7, in dose-dependent maanner. Additionally, gelsemine increased the reactive oxygen species (ROS) generation, again depending on the dose. In terms of protein expression, pretreatment with the antioxidant N-acetyl-l-cysteine (NAC) reversed the increases in PARP and caspase-3/-7 caused by gelsemine. Gelsemine effectively increased the levels of JNK1/2 phosphorylation while not affecting ERK1/2 and p38 phosphorylation. Pretreatment with the specific JNK inhibitor SP600125 reversed the increases cleaved PARP and caspase-3/-7 caused by gelsemine. Both NAC and SP600125 reduced the increases in JNK1/2 phosphorylation, ROS generation and caspase-3/-7 activity caused by gelsemine. The results of the present study collectively suggested that gelsemine induces apoptosis through a ROS- and JNK1/2 -coregulated pathway. To the best of our knowledge, this study is the first to demonstrate that gelsemine may be a potential therapeutic agent for tongue SCC.