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Page 8 of 15 Chen et al. Hepatoma Res 2018;4:29 I http://dx.doi.org/10.20517/2394-5079.2018.18

INHIBITORS OF INFLAMMATION FOR THE PREVENTION AND TREATMENT OF LIVER CANCER
As mentioned above, a large number of in vitro and in vivo experiments and some clinical studies have
confirmed that chronic inflammation plays a key role in the development of HCC. Understanding the
cytokines and signaling pathways required for the transmission of inflammation in HCC is more conducive
to understanding the occurrence of HCC development, and can also provide some reference value for
drug research and development. The following will discuss in detail some anti-inflammation agents in the
potential of liver cancer treatment, which mainly was divided into two categories, natural medicine and
synthetic drugs.

Natural anti-inflammatory agents
Natural medicine refers to modern medicine system that has a certain pharmacological activity of animal
medicine, botanical medicine, mineral medicine, fruits, vegetables or spices. A large number of studies show
that many natural anti-inflammatory drugs also have both cancer prevention and treatment potential. Many
articles reported that natural products could be potentially used for the prevention and treatment of liver
cancer through diet.

Curcumin, a chemical derived from the rhizomes of some plants from the family Zingiberaceae, is a
diketone. Curcumin has a variety of pharmacological activities, including lipid-lowering, anti-tumor, anti-
[106]
inflammatory, gallbladder, anti-oxidation and other effects . Existing research shows that curcumin can
inhibit DEN-induced NF-κB expression in liver tissue. Curcumin can also inhibit DEN-induced HCC by
[107]
inhibiting the expression of IL-2 and IL-6 and promoting Gpx, GRE and SOD activities . El-Houseini et al.
[108]
found that curcumin and taurine combination may be a new way to prevent liver cancer.

In 1940, resveratrol was first isolated from the roots of the leaf-walnut. In recent years, many studies
have shown that resveratrol has anti-cancer, anti-cardiovascular disease, weight loss, anti-bacterial, anti-
inflammatory, anti-oxidation pharmacological properties . In vitro experiments showed that the migration
[109]
and invasion of HepG2 cells are inhibited by resveratrol, which decrease the expression of MMP-2, MMP-9
and NF-κB nuclear transfer [110,111] . Resveratrol was also been shown to inhibit SIRT1 mediated PI3K/AKT
[112]
pathway, thereby down-regulating Bcl-2, caspase-3 and caspase-7 expression . DMU-212, a resveratrol
analogue, has been reported to have effect on antioxidant status and apoptosis-related genes in rat model of
hepatocarcinogenesis .
[113]

N-acetylcysteine (NAC), a water soluble organosulfur compound present in garlic, is a classic anti-oxidant.
Studies have shown that abnormal oxidative stress occurs in hepatocarcinoma. When NAC is used in hepatic
[114]
stellate cells (HSCs), it can inhibit hepatic fibrosis and HCC development . Moreover, the use of NAC in
HCC mice inhibited the high expression of GST, which may be related to insulin-like growth factor I (IGF-I)
and iNOS [115,116] .

Gallic acid (GA) is an organic acid, which is the main component of many herbs such as dogwood and
rhubarb. Experimental studies have shown that GA can inhibit the proliferation of HepG2 cells by inhibiting
[117]
the expression of IL-8 and promoting the expression of IL-10 and IL-12 . In the SMMC-7721 cells, GA
induced caspase-3, caspase-9 and reactive oxygen species (ROS) activity . N-nitrosodiethylamine induces
[118]
the high serum levels of alpha-fetoprotein, glypican-3, and STAT3. Those can all be inhibited by GA through
activation of p38 in HepG2 to produce anti-oxidant effect .
[119]

Flavonoids are a class of secondary metabolites of plants derived from a wide range of sources and can be
derived from fruits, vegetables, roots, stems, flowers, beans, and daily intake of beverages such as tea and
wine. Among them, baicalein, quercetin and genistein are three simpler and more studied agents. Baicalein
is derived from plant scutellaria baicalensis. Studies have reported that baicalein can inhibit the proliferation