Tetrahydro Iso-Alpha Acids and Hexahydro Iso-Alpha Acids from Hops Inhibit Proliferation of Human Hepatocarcinoma Cell Lines and Reduce Diethylnitrosamine Induced Liver Tumor Formation in Rats.
Chronic inflammation plays important role in the pathogenesis of hepatocellular carcinoma (HCC). To date, no antiinflammatory approach has shown its efficacy in preventing HCC occurrence in humans. Because tetra- and hexahydro isoalpha acids (THIAA and HHIAA) from hops elicit antiinflammatory properties, we evaluated these compounds for antitumor effects in vitro in human HCC cell lines (HepG2, Hep3B, Huh7) and in vivo in diethylnitrosamine (DEN)-induced animal model of HCC. In human HCC cell lines, THIAA and HHIAA reduced cell proliferation and viability which was associated with the inhibition of the NF-κB-DNA binding and tumor necrosis factor α mRNA expression. Both compounds also inhibited phosphorylation of the mTOR effector p70S6 kinase without affecting ERK, AKT, JNK, and GSK3β phosphorylation or activator protein-1 activation. In DEN-treated rats, administration of THIAA and HHIAA in food reduced the tumor numbers and the expression of the cellular transformation marker glutathione-S-transferase in the liver. In conclusion, THIAA and HHIAA show antitumor properties in vitro in human HCC cell lines as well as in vivo in a chemically induced animal model of HCC.
a Institut de Recherche Expérimentale et Clinique, Pôle Hépato-gastroentérologie, Université catholique de Louvain , Brussels , Belgium and Department of Gastroenterology, Cliniques Universitaires St. Luc , Brussels , Belgium.
Peter
P
Stärkel
Christine
C
De Saeger
Bénédicte
B
Delire
Julie
J
Magat
Bénédicte
B
Jordan
Veera R
VR
Konda
Mathew L
ML
Tripp
Ivan
I
Borbath
D000818:Animals; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D004353:Drug Evaluation, Preclinical; D006801:Humans; D027582:Humulus / Q000737:chemistry*; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D023421:Models, Animal; D016328:NF-kappa B / Q000235:genetics; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D016328:NF-kappa B; D010936:Plant Extracts; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D038762:Ribosomal Protein S6 Kinases, 70-kDa