Protective effects of coffee consumption following liver transplantation for hepatocellular carcinoma
03 January 2018 (online)
Increasing evidence suggests that coffee consumption might protect against
hepatocellular carcinoma (HCC) and liver cirrhosis associated death risk. Caffeine i
s a natural antagonist to extracellular adenosine and exhibits experimental tumoricidal activity. Coffee consumption of patients before and after orthotopic liver transplantat
ion (OLT) for HCC, from 2002 to 2012, was assessed and correlated with HCC recurrence. HepG2 cells were analysed for proliferation and metastasis potential after treatment with adenosine, in the presence or absence of adenosine receptor antagonists. Expression of adenosine receptors was determined, and known adenosine3mediated cancer pathways inclusive of MAPK (ERK and JNK) and NF3kappa B were tested.
90 patients underwent OLT for HCC. Sixteen (17.8%) patients experienced HCC
recurrence after median time of 11.5 months (range 1 3 40.5). In patients with a high preoperative or postoperative coffee intake (≥3 cups per day), HCC recurrence was observed less frequently than in those with lower coffee intake (less than ≤2 cups per day) (p = 0.018). HepG2 tumor cells express abundant levels of A2A and A2B receptors and show an intrinsic capacity to generate extracellular adenosine. Exogenous adenosine promotes HCC cell growth and metastasis in vitro. These actions are markedly blocked by antagonist to A2A receptor but not by a more specific antagonist to A2B receptor. Moreover, adenosine induces activation of MAPK (ERK and JNK) and NF3kappa B pathways, which can be counteracted by antagonism of A2A or A2B receptor. Conclusion: Coffee consumption is associated with a decreased risk of HCC
recurrence and provides for increased survival following OLT. We suggest that these results might be, at least in part, associated with the antagonist activity of caffeine on adenosine3A2AR mediated growth3promoting effects on HCC cells.