title: Pharmacological induction of leukotriene B4-12-hydroxydehydrogenase suppresses the oncogenic transformation of human hepatoma HepG2 cells.
abstract: Leukotriene B4-12-hydroxydehydrogenase (LTB4DH) is characterized as a chemopreventive and tumor suppressor gene. The aim of this study was to investigate the pharmaco-logical induction of LTB4DH and potential anticancer activity. Using HepG2 cells as a cellular detector, we successfully isolated the active compounds from the herbs Radix Astragali and Radix Paeoniae Rubra through a bioactivity-guided fractionation procedure. Using various analytical techniques including electronic spray ionization-mass spectrometry (ESI-MS) and nuclear magnetic resonance (NMR), gallic acid (GA) was identified as the active compound from Radix Paeoniae Rubra whereas the active compound from Radix Astragali, designated as RA-C, was also purified to the extent that it is now suitable for further identifi-cation. We found that the active compounds from these two different herbs synergistically induced LTB4DH expression in a dose- and time-dependent manner. A key finding was that commercial GA in combination with purified RA-C attenuated the focus formation and anchorage-independent growth, two indexes of in vitro oncogenic transformation, of HepG2 cells via the induction of LTB4DH expression. Moreover, the combination of GA and purified RA-C significantly induced G2/M cell cycle arrest in HepG2 cells. Our results demon-strated for the first time that GA and purified RA-C suppress the in vitro oncogenic transformation of HepG2 cells via the induction of LTB4DH expression. Importantly, pharmaco-logical induction of LTB4DH represents a potential alternative strategy for the therapy of hepatocellular carcinoma.
authors.affiliation: School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong, SAR, PR China.
authors.forename: Lai
authors.initials: L
authors.lastname: Wei
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: X Chris
authors.initials: XC
authors.lastname: Le
authors.forename: Yifan
authors.initials: Y
authors.lastname: Han
authors.forename: Yao
authors.initials: Y
authors.lastname: Tong
authors.forename: Allan S Y
authors.initials: AS
authors.lastname: Lau
authors.forename: Jianhui
authors.initials: J
authors.lastname: Rong
mesh_terms: D000429:Alcohol Oxidoreductases / Q000096:biosynthesis*; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D056945:Hep G2 Cells / Q000378:metabolism*; D006801:Humans; D029596:Paeonia / Q000737:chemistry; D010936:Plant Extracts / Q000494:pharmacology; D014162:Transfection
chemical_list: D010936:Plant Extracts; D000429:Alcohol Oxidoreductases; C082646:leukotriene B4 12-hydroxydehydrogenase