Diallyl Disulfide Blocks Cigarette Carcinogen 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone-Induced Lung Tumorigenesis via Activation of the Nrf2 Antioxidant System and Suppression of NF-κB Inflammatory Response.

Chemoprevention is a potential strategy to reduce lung cancer incidence and death. Recently, we reported that garlic oil significantly inhibits 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis. Diallyl disulfide (DADS) is a bioactive ingredient in garlic. Our goal was to examine the chemopreventive effectiveness and mechanism of DADS on NNK-triggered lung cancer in vivo and in vitro in the current investigation. The results indicated that DADS significantly reduced the number of lung nodules in the NNK-induced A/J mice. Consistent with the in vivo results, DADS markedly inhibited NNK-induced decrease of MRC-5 cells' viability. Mechanistically, DADS could promote Nrf2 dissociated from the Keap1-Nrf2 complex and accelerate Nrf2 nuclear translocation, which in turn upregulates its downstream target genes. Besides, DADS further inhibited the NF-κB signaling cascade, thus reducing the accumulation of inflammatory factors. Collectively, these discoveries supported the potential of DADS as a novel candidate for the chemoprevention of tobacco-carcinogen-induced lung cancer.