Curcumin, a yellow
polyphenol extracted from the rhizome of
turmeric root (Curcuma longa) has potent anti-
cancer properties in many types of
tumors with ability to reverse multidrug resistance of
cancer cells. However, widespread clinical application of this agent in
cancer and other diseases has been limited due to its poor aqueous solubility. The recent findings of polymeric nanoparticle formulation of
curcumin (NFC) have shown the potential for circumventing the problem of poor solubility, however evidences for NFC's anti-
cancer and reverse multidrug resistance properties are lacking. Here we provide models of human
hepatocellular carcinoma (HCC), the most common form of primary
liver cancer, in vitro and in vivo to evaluate the efficacy of NFC alone and in combination with
sorafenib, a
kinase inhibitor approved for treatment of HCC. Results showed that NFC not only inhibited the proliferation and invasion of HCC cell lines in vitro, but also drastically suppressed primary
tumor growth and lung
metastases in vivo. Moreover, in combination with
sorafenib, NFC induced HCC cell apoptosis and cell cycle arrest. Mechanistically, NFC and
sorafenib synergistically down-regulated the expression of MMP9 via NF-κB/p65 signaling pathway. Furthermore, the combination
therapy significantly decreased the population of CD133-positive HCC cells, which have been reported as
cancer initiating cells in HCC. Taken together, NanoCurcumin provides an opportunity to expand the clinical repertoire of this agent. Additional studies utilizing a combination of NanoCurcumin and
sorafenib in HCC are needed for further clinical development.