6-Gingerol alleviates NNK-induced lung carcinogenesis by boosting antioxidation and reducing inflammation

With lung cancer rates climbing steadily, the development of effective prevention strategies has become more crucial than ever. Our previous research has revealed that ginger oil possesses potential lung cancer preventive activity, demonstrating inhibitory effects against tobacco carcinogen 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung cancer in A/J mice. 6-Gingerol, a bioactive compound from ginger (Zingiber officinale Rosc.), exhibits multiple pharmacological activities. However, the preventive efficacy of 6-Gingerol against tobacco carcinogen-induced lung cancer remains unclear. This study investigated the chemopreventive effects of 6-Gingerol on NNK-induced lung tumorigenesis in A/J mice and Beas-2b cells. Results indicated that 6-Gingerol significantly reduced lung tumor count and improved tissue structure compared to NNK alone. In vitro, 6-Gingerol protected Beas-2b cells from NNK-induced damage. Mechanistically, 6-Gingerol activated the Nrf2 pathway, enhancing antioxidant enzyme expression and reducing oxidative stress. Additionally, 6-Gingerol exhibited anti-inflammatory effects by inhibiting the NNK-activated TLR4/NF-κB pathway. In conclusion, 6-Gingerol shows significant chemopreventive effects against NNK-induced lung cancer via activating Nrf2 and suppressing TLR4/NF-κB, underscoring its potential as a preventive agent functional food in lung cancer development.