Hepatocellular carcinoma (HCC) is one of the most common
cancers in the world and one of the most lethal. MGN-3/
Biobran is a
natural product derived from rice bran hemicelluloses and has been reported to possess a potent anticancer effect in a clinical study of patients with HCC. The current study examines the mechanisms by which
Biobran protects against chemically induced hepatocarcinogenesis in rats. The chemical
carcinogen used in this study is
N-nitrosodiethylamine (NDEA) plus
carbon tetrachloride (CCl4). Rats were treated with this
carcinogen, and the animals were pretreated or posttreated with
Biobran via
intraperitoneal injections until the end of the experiment. Treatment with
Biobran resulted in: 1) significant alleviation of liver preneoplastic lesions towards normal hepatocellular architecture in association with inhibition of
collagen fiber deposition; 2) arrest of
cancer cells in the sub-G1 phase of the cell cycle; 3) increased DNA fragmentation in
cancer cells; 4) down-regulated expression of Bcl-2 and up-regulated expression of p53, Bax, and
caspase-3; and 5) protection against
carcinogen-induced suppression of
IkappaB-alpha (IκB-α)
mRNA expression and inhibition of
nuclear factor kappa-B (NF-κB/p65) expression. Additionally, the effect of
Biobran treatment was found to be more significant when supplemented prior to
carcinogen-induced hepatocarcinogenesis as compared to posttreatment. We conclude that
Biobran inhibits hepatocarcinogenesis in rats by mechanisms that include induction of apoptosis, inhibition of
inflammation, and suppression of
cancer cell proliferation.
Biobran may be a promising chemopreventive and chemotherapeutic agent for liver
carcinogenesis.