Carcinogenesis, Vol 19, 2133-2138, Copyright © 1998 by Oxford University Press
WJ Chi, SL Doong, SY Lin-Shiau, CW Boone, GJ Kelloff and JK Lin
Molecular epidemiological studies of populations at high risk for liver
cancer have shown that hepatitis B virus (HBV) and aflatoxin B1 exposures
are two major risk factors for this disease. Oltipraz is currently being
considered for clinical trial to protect against aflatoxin B1-induced
hepatocarcinogenesis based on its proven protective effect in many
different animal models. In addition, oltipraz inhibits human
immunodeficiency virus (HIV) replication. The inactivation of reverse
transcriptase of HIV appears to be the antiviral mechanism. It has been
demonstrated that a number of compounds that inhibit HIV replication also
inhibit HBV replication in vitro. Therefore, we tested the possibility of
oltipraz blocking HBV replication in 2.2.15 cells (clonal cells derived
from HepG2 cells that were transfected with a plasmid containing HBV DNA)
in vitro. Results of the experiments indicate that oltipraz has a
dose-dependent inhibitory effect on HBV replication and specifically blocks
HBV transcription in 2.2.15 cells. In addition, oltipraz induces endogenous
wild-type p53 protein in a dose- and time-course-dependent manner. Taken
together, we speculate that the effects of oltipraz against replication of
HBV and specific blocking of HBV transcription may be through the induction
of p53-mediated pathway in 2.2.15 cells. In addition to its known
chemopreventive action on aflatoxin B1 hepatocarcinogenesis, oltipraz was
shown here to inhibit HBV replication. These dual effects put oltipraz as
the excellent candidate for the chemopreventive agent of human
hepatocellular carcinoma.
ARTICLES
Oltipraz, a novel inhibitor of hepatitis B virus transcription through elevation of p53 protein
Institute of Biochemistry, College of Medicine, National Taiwan University, No. 1, Section 1, Taipei.
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