Background: It is well established that nicotine produces hyperpolarizing inward rectifying potassium currents which suppress apoptosis in nervous tissue. Furthermore, inhibition of nicotinic receptors depolarize nerve cells resulting in cell death. We have recently shown that constitutively active nicotinic receptors maintain the survival of human KB oral carcinoma cells. Objective: To determine whether the prosurvival effects of nicotine in KB oral carcinoma cells are due in part to alterations in potassium transport. Methods: Human KB oral carcinoma cells were treated for 24 hours at 37oC with vehicle, nicotine, mecamylamine (nicotinic receptor antagonist), or barium chloride (potassium channel inhibitor) alone and in combination with the nicotine analogs. Cell viability was examined using the MTT assay and relative changes in AkT, p-AkT (active anti-apoptotic protein), PTEN (proapoptotic enzyme; degrades p-AkT) and p-PTEN were determined by western blot analysis. All experiments were performed in triplets. Results: Nicotine or barium chloride alone had no effect on baseline cell viability, while, mecamylamine induced cell death in 50% of the cells (p<0.05; n=3-7). Additionally, mecamylamine reduced active p-AkT expression and increased PTEN levels. Pretreatment with barium chloride prevented the mecamylamine-induced apoptosis (p<0.05; n=3-7). On the other hand, barium chloride had no effect on the inhibitory effect of mecamylamine on p-Akt levels. Conclusion: The results suggest that nicotine, a tobacco additive, promotes the survival of human KB oral carcinoma cells by two distinct mechanisms involving the stimulation of p-AkT levels and alterations in potassium transport across the cell membrane. Supported by LEQSF HEF (2001-2005)-05 and NCI Fellowship.

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