Caffeine improves diethylnitrosamine-induced hepatocellular carcinoma by inhibiting cAMP/PKA/CREB signaling in rats
Year: 2025
Type: article
Abstract: 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. • Diethylnitrosamine (DEN) led to hepatocellular carcinoma (HCC) in all animals. • Caffeine has a protective effect on DEN-induced HCC by modulating downstream cAMP/PKA/CREB signaling via A2AR. • Caffeine inhibited A2AR to downregulate the proliferation, migration, invasion, and induce the apoptosis of HCC cells. • Protective effect of caffeine on HCC was achieved through its competitive inhibition of A2AR.
Authors: Liang Shan, Chuanying Wang, Xing Fang, Zhengsheng Zhang, Shujuan Dai, Jianjun Liu
Institutions: Anhui Medical University, Anhui Institute of Medicine
Language: English
Topic: Coffee research and impacts
Subfield: Pharmacology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,700
Awards: G1375782719, G244549648
OpenAlex ID: W4414997461