Introduction: Nicotine is a key biologically active compound of cigarettes. Although nicotine is a risk factor for various health issues, it may also be beneficial when treated at moderate concentrations. Nicotine has been shown to bidirectionally regulate stem cell proliferation and differentiation depending on the doses applied. It is not clear whether or how nicotine regulates mouse embryonic stem cell (mESC) survival and proliferation. Methods: Mouse embryonic stem cells were cultured in the presence of 0.01, 0.1, 1, or 10 μM nicotine. The effects of nicotine on cell survival and proliferation were examined. The signaling pathway that mediated these effects was analyzed. Results: Cell viability was not affected by nicotine at all 4 concentrations examined. The proliferation of mESCs was promoted by 0.01 and 0.1 μM nicotine and suppressed by 1 and 10 μM. This dose-dependent regulation was mediated through the Wnt/β-catenin pathway. Modulation of Wnt/β-catenin activity either worsens or reverses the effects of nicotine. Conclusions: We have identified a bidirectional function of nicotine on mESC proliferation through regulation of the Wnt/β-catenin pathway and this is associated with different doses. This study suggests that concentration of nicotine is a crucial aspect for consideration when designing research or therapeutic strategies.
Phospholipase C and protein kinase C involvement in mouse embryonic stem-cell proliferation and apoptosis
