Diallyl Trisulfide Suppresses 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone-Induced Lung Carcinogenesis via Modulating Keap1-Nrf2 Axis

Smoking remains strongly associated with lung cancer, underscoring the need for effective chemopreventive strategies derived from dietary sources. This study is focused on the protective effects of diallyl trisulfide (DATS) against 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) triggers lung tumor formation. DATS is a bioactive organosulfur compound sourced from garlic. In an A/J mouse model, DATS administration significantly reduced lung tumor multiplicity. In vitro assays using MRC-5 human lung fibroblasts demonstrated that DATS mitigated NNK-induced cytotoxicity. Mechanistic studies indicated that DATS-mediated Nrf2 pathway activation, via Keap1 dissociation and nuclear translocation, upregulates antioxidant defense genes. Critically, pharmacological inhibition of Nrf2 abolished the protective effects of DATS, pointing to the pathway as central to the effect. Our results position DATS as a promising candidate for dietary prevention of lung cancer. Taken together, this study suggests that DATS has promise as a dietary strategy to prevent lung cancer.