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Nicotine Inhibits Vit E Succinate-induced Apoptosis:Head/Neck

Nicotine inhibits vitamin E succinate induced apoptosis of human head neck squamous cell carcinoma.

Xinbin Gu, Xiaowu Pang, Yanfei Zhou, Rajagopalan Sridhar, Joseph Califano.

Howard University, Washington, DC; Johns Hopkins University, Baltimore, MD.

Tobacco use is a major risk factor for oral and pharyngeal cancers. After a cancer diagnosis, continued 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 several cancer cell lines. However, a clinical study at Finland failed to show efficacy of vitamin E in preventing oral mucosal changes among heavy smokers.

The effect of nicotine on VES induced apoptosis was studied in vitro using JHU-11, JHU-13, and JHU-29 human head and neck squamous cell carcinoma (HNCC) cultures. JHU-11 and JHU-13 cells containing mutated p53 genes were isolated from the larynx tissue and the neck node metastasis. JHU-29 cells having a wild type p53 gene were derived from base of tongue cancer.

Exponentially growing monolayer cultures of these cells were treated with 20ìM nicotine for 120 minutes, followed by a co-exposure to 70ìM VES-liposomes for 180, 360 and 720 minutes.

Apoptosis was assayed immediately after exposure to VES-liposomes. The inhibition of VES-induced apoptosis by 20mM nicotine could be demonstrated clearly using annexin V levels, cell cycle analysis, caspase-3 and caspase-8 activities respectively, and DNA fragmentation analysis.

Clonogenicity assays for cell viability also confirmed the ability of nicotine (20ìM) to protect JHU-11, JHU-13 and JHU29 against the cytotoxicity of a 180-minute treatment with VES-liposomes. 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.

In conclusion, nicotine inhibited VES- induced apoptosis in these JHU-HNSCC cells.

It may explain why VES is not effective in preventing oral cancer in heavy smokers.



AACR Abstract Number: 3894

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