Enhancement of the Anti-Hepatoma Activity of Acacetin Through Salt Formation of Sodium Acacetin.

Acacetin has wide anticancer properties. However, its water insolubility limits its clinical application. In this study, sodium acacetin was prepared by double decomposition reaction and characterized by differential thermal analysis, ultraviolet-visible spectroscopy, Fourier-transform infrared spectroscopy, inductively coupled plasma-mass spectrometry, and 1H nuclear magnetic resonance. In addition, the anti-hepatocellular carcinoma activity of sodium acacetin was investigated by using HepG2 cells and H22 tumor-bearing mice. When acacetin and sodium hydroxide react in a 1:2 molar ratio, they form acacetin monosodium salt and disodium salt in a 1.6:1 ratio. The solubility of the obtained mixed sodium acacetin was about 6000 times higher than that of acacetin. The formation of sodium acacetin was verified by the analysis method mentioned above. Moreover, sodium acacetin significantly inhibited cell proliferation and colony formation, arrested the cell cycle at G0/G1 phase, and induced apoptosis in HepG2 cells in a dose‑dependent manner. It exhibited a more significant antitumor effect than acacetin in H22 tumor-bearing mice. The current study provided a salt-formation strategy to improve the solubility and bioactivity of poorly water-soluble drugs and a possible drug form for further clinical treatment of liver cancer with acacetin.