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absence of vascular invasion. Several staging systems to “HCC” on PubMed to find studies that discussed their
[18]
have been developed for HCC, but the best and most roles in HCC. Articles were downloaded for reviewing and
widely used is Barcelona Clinic Liver Cancer classification; discussing natural products that had adequate studies in
added to the staging, it has prognostic and treatment treating HCC.
implication. [19]
CURCUMIN
There are different treatment options for HCC ranging
from loco-regional therapy (radiofrequency ablation, Curcumin is a polyphenol, a diferuloylmethane and it is among
arterial chemoembolization, intra-tumor ethanol injection, the three main curcuminoids present in turmeric. Curcumin
[18]
yttrium-90 intra-arterial delivery as microspheres, and is a potent anti-inflammatory agent. Curcumin has been
[30]
microwave coagulation) to surgical treatment (surgical proven to be effective in treating a variety of conditions
resection and liver transplantation) and sorafenib. [9,20,21] such as allergy, psoriasis, diabetes, rheumatoid arthritis,
Distinctive regimen of chemotherapy has been tried with asthma, and neurodegenerative diseases. Moreover, it
[18]
poor response. is cardioprotective, hepatoprotective, carcinoprotective,
[18]
and neuroprotective. As mentioned earlier, free radicals
Surgical treatment is the best present-day management generation is an important step in tumor formation,
options for HCC, but not all patients are eligible for it. and curcuminoids are known to inhibit oxidation owing
[12]
Surgical resection cannot be performed if the tumor is to their methoxy group, 1,3 β-diketone moiety, and
present in multiple sites, in advanced liver disease (Child’s B phenolic hydroxyl group. Curcumin was found to inhibit
[31]
and C) and in the presence of vascular invasion, and only nuclear factor-kB (NF-kB), which activated inflammatory
[21]
about 20% of patients are candidates for surgical resection. cytokines and chemokines, leading to several inflammatory
[22]
Early on, HCC was a contraindication for liver transplantation conditions. [32-34] NF-kB activation promotes cellular
due to poor result. Mazzaferro et al. published Milan proliferation, angiogenesis, and invasion and inhibits
[23]
criteria, in which patients with early disease have a good apoptosis. [35,36] In addition, curcumin also inhibits
outcome. A significant number of HCC patients do not meet interleukin-1 (IL-1), IL-1B, IL-6, IL-8, tumor necrosis alpha,
Milan criteria on presentation or drop out due to disease and cyclo-oxygenase pathways. [35,37-39] Several studies have
progression while waiting for liver transplantation due to the supported curcumin’s anti-oxidant and anti-inflammatory,
shortage of donors. Sorafenib, a tyrosine kinase inhibitor particularly in HCC. Dai et al. studied the anti-tumor
[27]
[23]
and vascular endothelial growth factor, is presently used effects of curcumin in vitro and in vivo. Curcumin inhibited
in managing unresected HCC. It increases the average HepG2’s proliferation in a dose and time dependent fashion,
[24]
survival time by 3 months in patients with late-stage HCC. with the most potent inhibition at a concentration of
[18]
However, sorafenib can be used in Child’s A and selected 8 umol/L for 48 h, it leads to HepG2 induced cells apoptosis
Child’s B patients, in addition to the side effect and high at high doses, the apoptosis rate increased up to 20% at
cost. [25,26] a curcumin concentration of 16 umol/L. In addition, high
doses of curcumin have been shown to elevate casepase-3,
Clearly, the available treatment option is far from optimal, an essential protein for apoptosis. [27] Curcumin has
either due to limited efficacy or contraindication due to restricted liver tumor growth in HepG2 xenograft mice
advanced liver disease (resection and loco-regional therapy models in vivo; the greatest reduction in tumor volume was
for Child’s C), this reiterates the need for new treatment around 3740 mm at a high curcumin dose of 60 mg/kg.
[27]
3
option. Curcumin also mediated apoptosis in HL60, SGC7901, and
Bel7402 cells by inhibiting telomerase activity. [40]
Several studies aimed at discovering more molecules
for the management of HCC. Those studies aimed at In another study by Lin et al., curcumin caused a decline
[41]
recognizing and targeting several signaling and molecular migration and invasion of SK-Hep-1 cells as well as matrix
pathways that lead to cellular proliferation and tumor metalloproteinase-9 (MMP-9) levels. Also, curcumin has an
formation. [12,27-29] inhibitory effect of vasculogenic mimicry in SK-Heo-1 cells,
a process in which hepatocytes act as endothelial cells
In this review, we discussed the role of several agents and form blood vessels, by inhibiting the STAT3 and Akt
found in natural and dietary products such as curcumin, pathways. Moreover, curcumin decreases caveolin-1 levels
[42]
resveratrol, flavonoids, Rubus aleaefolious Poir total alkaloids, and epidermal growth factor signaling, and therefore may
Livistona chinensis seed, and crocetin. We had used the names prevent vascular invasion and metastasis. Unfortunately,
[40]
of the above-mentioned products as key words in addition curcumin has poor pharmacokinetics as it undergoes poor

120 Hepatoma Research | Volume 1 | Issue 3 | October 15, 2015