Toluquinol modulates NR1D1 and circadian rhythm in lung cancer cells: Implications for circadian medicine

Lung cancer remains one of the most fatal cancers, with cigarette smoke (CS) exposure being a major risk factor due to its role in triggering oxidative stress. Disruption of circadian rhythms, increasingly common in modern lifestyles, has also been linked to cancer progression. Targeting both oxidative imbalance and circadian disruption may offer a more effective therapeutic approach. Toluquinol (TQ), a compound derived from marine fungi, has shown promising anti-tumor activity and potential relevance in circadian-based cancer strategies. The current study investigated the role of TQ as a potential circadian medicine in modulating the dysregulated circadian-regulatory gene expression in the CS-exposed NCI-H23 lung adenocarcinoma cell line. Among the core circadian regulatory genes, NR1D1 plays a crucial role as a transcriptional repressor, involved in maintaining the circadian rhythm, regulating redox homeostasis, and modulating inflammation. Dysregulation of NR1D1 has been linked to cancer progression and poor prognosis in lung cancer. This study offers valuable insights into the impact of CS on NR1D1 gene regulation and its role in lung cancer development, which is mediated through disrupted redox balance and inflammation, while highlighting the potential therapeutic role of TQ in mitigating this process.