title: Low Concentration of Caffeine Inhibits the Progression of the Hepatocellular Carcinoma via Akt Signaling Pathway.
abstract: Accumulating evidences have reported that caffeine has anticancer effects at high blood concentrations. However, whether caffeine has anticancer effects on human hepatocellular carcinoma (HCC) cells at low concentration, especially at physiologically applicable concentration (< 412 μM) is still not well understood. In this study, HCC cell lines HepG2 and Huh7 were used. The cells were incubated with varying concentrations of caffeine (0, 50, 100, 200, 400 or 600 μM). MTT assay was used to investigate the proliferation ability in vitro. Migration and invasion abilities were determined by wound healing assay and transwell assay. The molecular changes were detected by western blot. An ectopic nude mice model which the mice were gavaged with caffeine was used to reveal the anticancer effects of caffeine on HepG2 cells in vivo. Results showed that caffeine could inhibit the proliferation, migration and invasion significantly at physiologically applicable concentration in vitro. Also the associated molecular changes of cancer progression were observed. In animal experiment, the mice gavaged with caffeine also performanced reduced tumor burden in vivo. Moreover, the interrelated protein expression was also observed in vivo which was coincident with the results in vitro. All in all, this observation indicated that caffeine may suppress the progression of HCC through Akt signaling pathway. This makes caffeine a potential candidate for treating HCC which will be a safer and more effective treatment by giving for a long time at physiologically applicable concentration.
authors: Shuying
authors: S
authors: Dong
authors: Jian
authors: J
authors: Kong
authors: Jinge
authors: J
authors: Kong
authors: Qiang
authors: Q
authors: Shen
authors: Fandong
authors: F
authors: Kong
authors: Wenbing
authors: W
authors: Sun
authors: Department of Hepatobiliary Surgery, Beijing Chao-yang Hospital, Capital Medical University, Beijing 100043, China. cyhswb@qq.com.
authors: Lemin
authors: L
authors: Zheng
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002110:Caffeine / Q000494:pharmacology* / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D064593:Heterografts; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D018919:Neovascularization, Physiologic / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D002110:Caffeine; D051057:Proto-Oncogene Proteins c-akt