Caffeine improves diethylnitrosamine-induced hepatocellular carcinoma by inhibiting cAMP/PKA/CREB signaling in rats

Studies have shown that long-term coffee consumption is significantly inversely associated with the risk of hepatocellular carcinoma (HCC). It has been shown that caffeine (a naturally occurring compound) can inhibit HCC in animal models. However, the mechanism of caffeine on the prevention and treatment of HCC has not been fully clarified. Diethylnitrosamine (DEN) is considered a potent carcinogen. Based on literature in China and overseas, we adopted a DEN-induced HCC model in rats to observe the preventive and therapeutic effects of caffeine on HCC induced by DEN in rats and elucidate the mechanisms. We found that caffeine had protective effects on HCC induced by DEN in rats through inhibition of ‌cyclic adenosine monophosphate-protein kinase A-cAMP-response element binding protein‌ (cAMP-PKA-CREB) signaling. This study provides: (i) an in vivo and in vitro experimental basis for the application of caffeine in the clinical prevention and treatment of HCC; (ii) new perspectives for the evaluation and screening of efficacious drugs for the prevention and treatment of HCC.