Abstract
Chronic hepatitis B virus (HBV) infection is a major risk factor for the development of hepatocellular carcinoma (HCC), a leading cause of cancer mortality worldwide. Hepatitis B X protein (HBx) and pre-S2 mutant have been proposed as the two most important HBV oncoproteins that play key roles in HCC pathogenesis. Curcumin is a botanical constituent displaying potent anti-inflammatory and anti-cancer properties without toxic side effects. Phytosomal formulation of curcumin has been shown to exhibit enhanced bioavailability, improved pharmacokinetics, and excellent efficacy against many human diseases. However, effectiveness of phytosomal curcumin for HCC treatment remains to be clarified. In this study, we evaluated chemopreventive effect of phytosomal curcumin on HBV-related HCC by using a transgenic mouse model specifically expressing both HBx and pre-S2 mutant in liver. Compared with unformulated curcumin, phytosomal curcumin exhibited significantly greater effects on suppression of HCC formation, improvement of liver histopathology, decrease of lipid accumulation and leukocyte infiltration, and reduction of total tumor volume in transgenic mice. Moreover, phytosomal curcumin exerted considerably stronger effects on activation of anti-inflammatory PPARγ as well as inhibition of pro-inflammatory NF-κB than unformulated curcumin. Furthermore, phytosomal curcumin showed a comparable effect on suppression of oncogenic mTOR activation to unformulated curcumin. Our data demonstrated that phytosomal curcumin has promise for HCC chemoprevention in patients with chronic HBV infection.