Inhibition of pulmonary carcinogenesis in mouse models of lung cancer by antitumor B.

ED06-03

Antitumor B (ATB) is a Chinese herbal mixture of six plants. Previous studies have shown significant chemopreventive efficacy of ATB against human esophageal and lung cancers. Here, we determined the effect of ATB on the development of lung adenomas and adenocarcinomas using two different protocols (complete and progression) and on the development of lung squamous cell carcinomas (SCC). Treatment with ATB caused a significant reduction in both tumor multiplicity and tumor volume in the complete protocol and reduced the progression of adenomasto adenocarcinomas. Moreover, ATB treatment inhibited the development of lung SCCs by more than 3-fold. Small-animal imaging techniques (MRI and CT) were employed for characterization of mouse lung adenocarcinomas and SCCs. Next, ATB was enriched via extraction with decreasing concentrations of ethanol in water, resulting in four fractions. The three useable fractions were designated FA, FB, and FC. These enriched fractions, together with ATB, were used to determine their effects on cell growth, cell cycle regulation, and transactivation of activated protein 1 (AP-1). Treatment of a mouse lung tumor cell line (MC7) with ATB and its fractions caused cell growth inhibition, and arrested the cells at G1 phase of cell cylce. Promoter assay of AP-1 showed that ATB and its fractions caused a decrease of AP-1 activity. The effect of ATB on AP-1 appears to be mediated by inhibition of mitogen-activated protein kinases (MAPK). ATB and the fraction FA showed a similar effect on the MAPK/AP-1 signaling pathway. These results suggest that ATB is a potent inhibitor of pulmonary carcinogenesis of both adenocarcinomas and squamous cell carcinomas, at least in part, mediated, at least in part, by impairing signaling pathways leading to activation of AP-1.