Nicotine Inhibits Vitamin E Succinate-induced Apoptosis of Human Oral Cancer Cells

The one major risk factor for oral and pharyngeal cancers is use of tobacco, and after a cancer diagnosis use of tobacco decreases survival, promotes recurrence, and decreases the efficacy of cancer therapy. The chemopreventive agent vitamin E succinate (a tocopherol succinate, VES) induces apoptosis in cancer cells. However, a clinical study has demonstrated the lack of efficacy of vitamin E in preventing oral mucosal changes among heave smokers3. Objective: this study is to evaluate the effect of nicotine on VES induced apoptosis in vitro using JHU-019 human oral cancer cultures. Methods: Exponentially growing monolayer cultures of JHU-019 cells were treated with 20uM nicotine for 120 minutes, followed by a co-exposure to 70uM VES for 180, 360 and 720 minutes. Apoptosis was assayed immediately after exposure to VES in various treatment times. Results: The inhibition of VES-inducted apoptosis by 20uM nicotine could be demonstrated clearly using annexin V levels, cell cycle analysis, caspase-3 and caspase-8 activities respectively, and DNA fragmentation analysis. Clonogenicity assay for cell viability also confirmed the ability of nicotine (20uM) to protect JHU-019 against the cytoxicity of a 180 minutes treatment with VES. However, nicotine by itself had no effect on apoptosis, although it inhibited VES induced apoptosis. Apoptosis is a defense mechanism against carcinogenesis. If nicotine inhibits apoptosis in normal cells or cells progressing towards malignancy, then the risk of malignancies may be higher in smokers, whom use tobacco products. It may also explain why had a low efficacy of VES in preventing oral cancer among heave smokers. Conclusions: nicotine selectively prevent vitamin E succinate induced apoptosis.