Diallyl trisulfide inhibits 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung cancer via modulating gut microbiota and the PPARγ/NF-κB pathway

Smoking is the primary risk factor for developing lung cancer. Chemoprevention could be a promising strategy to reduce the incidence and mortality rates of lung cancer. Recently, we reported that A/J mice exposed tobacco smoke carcinogens displayed the reshape of gut microbiota. Additionally, garlic oil was found to effectively inhibit the carcinogen effects of tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in lung tumorigenesis. Diallyl trisulfide (DATS), which is the predominant compound in garlic oil, exhibits various biological activities. To further explore the chemopreventive action and potential mechanism of DATS on lung tumorigenesis, we established a lung adenocarcinoma model in A/J mice stimulated by NNK. Subsequently, we employed multi-omics combined molecular biology technologies to clarify the mechanism. The results indicated that DATS significantly decreaseed the number of lung nodules in NNK induced A/J mice. Interestingly, we discovered that DATS could modulate gut microbiota, particularly suppressing the growth of F. rodentium, which has inhibitory effects on tumor growth. Mechanistically, DATS could activate the PPARγ pathway, leading to the negative regulation of NF-κB signaling pathway and subsequent suppression of NF-κB-mediated inflammatory factors. Collectively, these findings provide support for DATS as a potential novel chemopreventive agent for tobacco carcinogen-induced lung cancer.

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