Caffeine inhibits the proliferation of liver cancer cells and activates the MEK/ERK/EGFR signalling pathway.
Caffeine has been reported to prevent hepatocarcinogenesis. We investigated the molecular mechanisms by which caffeine inhibits the growth of hepatocellular carcinoma (HCC) cells. We found that caffeine inhibited the proliferation of HCC cells via cell cycle arrest independent of apoptosis. We revealed a novel signalling axis for caffeine involving activation of the mitogen-activated ERK-regulating kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway that resulted in the downstream up-regulation of epidermal growth factor receptor (EGFR), although the MEK/ERK/EGFR signalling pathway was not involved in the growth inhibitory effect of caffeine. Our data reveal that caffeine could be a promising candidate for the treatment of patients with HCC.
Okano
Jun-ichi
J
Second Department of Internal Medicine, Tottori University School of Medicine, Tottori, Japan. okanoj@hotmail.co.jp
Nagahara
Takakazu
T
Matsumoto
Kazuya
K
Murawaki
Yoshikazu
Y
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002110:Caffeine / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004273:DNA, Neoplasm / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D066246:ErbB Receptors / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D002110:Caffeine; D066246:ErbB Receptors; D048049:Extracellular Signal-Regulated MAP Kinases; D020930:MAP Kinase Kinase Kinases