Lung cancer is the most fatal cancer and development of agents that suppress 
lung tumorigenesis is a crucial strategy to reduce mortality related to this 
disease. In the present study, we showed, using an in vitro model of lung 
tumorigenesis, that dimethylamino-parthenolide (DMAPT), a water soluble 
parthenolide analog, selectively inhibited the growth and survival of 
premalignant and malignant cells with minimal effects on parental immortalized 
cells. These effects were paralleled by suppression of pSTAT3, Mcl-1 and cyclin 
D1 and PARP cleavage, suggesting that the antiproliferative and apoptotic 
effects of DMAPT could be mediated, at least in part, via suppression of the 
STAT3 signaling pathway. Moreover, in tobacco smoke carcinogen-induced lung 
tumor bioassay in mice, intranasal instillation of low doses of DMAPT 
significantly reduced the overall lung tumor multiplicity by 39%. Interestingly, 
the drug was specifically effective (62% reduction) against bigger lung tumors 
(> 2 mm), which have a higher potential to develop into lung adenocarcinoma. 
Western immunoblotting analyses of mouse lung tissues indicated significantly 
lower level of pSTAT3 and Mcl-1 in the carcinogen plus DMAPT group relative to 
the group treated with the carcinogen only. Given the evidence that STAT3 is 
activated in more than half of lung cancers and it regulates genes involved in 
cell proliferation, survival and angiogenesis, DMAPT is a promising agent for 
lung cancer chemoprevention in subjects who are at high risk of developing this 
devastating disease.