Zn(II)-curcumin solid dispersion impairs hepatocellular carcinoma growth and enhances chemotherapy by modulating gut microbiota-mediated zinc homeostasis

Publication date: Available online 14 September 2019Source: Pharmacological ResearchAuthor(s): Rihui Wu, Xueting Mei, Yibiao Ye, Ting Xue, Jiasheng Wang, Wenjia Sun, Caixia Lin, Ruoxue Xue, Jiabao Zhang, Donghui XuAbstractZinc(II) complexes of curcumin display moderate cytotoxicity towards cancer cells at low micromolar concentrations. However, the clinical use of zinc(II) complexes is hampered by hydrolytic insolubility and poor bioavailability and their anticancer mechanisms remain unclear. Here, we investigated the efficacy and mechanism of action of a polyvinylpyrrolidone (PVP-k30)-based solid dispersion of Zn(II)-curcumin (ZnCM-SD) against hepatocellular carcinoma (HCC) in vitro and in vivo. In vitro assays revealed ZnCM-SD not only reduced the viability of HepG2 cells and SK-HEP1 cells in a dose-dependent manner, but also potently and synergistically enhanced cell growth inhibition and cell death in response to doxorubicin by regulating cellular zinc homeostasis. ZnCM-SD was internalized into the cells via non-specific endocytosis and degraded to release curcumin and Zn2+ ions within cells. The anticancer effects also occur in vivo in animals following the oral administration of ZnCM-SD, without significantly affecting the weight of the animals. Interestingly, ZnCM-SD did not reduce tumor growth or affect zinc homeostasis in HepG2-bearing mice after gut microbiome depletion. Moreover, administration of ZnCM-SD alone or in combination with doxorubicin significantly atten...
Source: Pharmacological Research - Category: Drugs & Pharmacology Source Type: research