Baicalein inhibits the migration and invasive properties of human hepatoma cells.

Abstract

Flavonoids have been demonstrated to exert health benefits in humans. We investigated whether the flavonoid baicalein would inhibit the adhesion, migration, invasion, and growth of human hepatoma cell lines, and we also investigated its mechanism of action. The separate effects of baicalein and baicalin on the viability of HA22T/VGH and SK-Hep1 cells were investigated for 24h. To evaluate their invasive properties, cells were incubated on matrigel-coated transwell membranes in the presence or absence of baicalein. We examined the effect of baicalein on the adhesion of cells, on the activation of matrix metalloproteinases (MMPs), protein kinase C (PKC), and p38 mitogen-activated protein kinase (MAPK), and on tumor growth in vivo. We observed that baicalein suppresses hepatoma cell growth by 55%, baicalein-treated cells showed lower levels of migration than untreated cells, and cell invasion was significantly reduced to 28%. Incubation of hepatoma cells with baicalein also significantly inhibited cell adhesion to matrigel, collagen I, and gelatin-coated substrate. Baicalein also decreased the gelatinolytic activities of the matrix metalloproteinases MMP-2, MMP-9, and uPA, decreased p50 and p65 nuclear translocation, and decreased phosphorylated I-kappa-B (IKB)-β. In addition, baicalein reduced the phosphorylation levels of PKCα and p38 proteins, which regulate invasion in poorly differentiated hepatoma cells. Finally, when SK-Hep1 cells were grown as xenografts in nude mice, intraperitoneal (i.p.) injection of baicalein induced a significant dose-dependent decrease in tumor growth. These results demonstrate the anticancer properties of baicalein, which include the inhibition of adhesion, invasion, migration, and proliferation of human hepatoma cells in vivo.

• Authors: Yung-Wei Chiu, Tseng-Hsi Lin, Wen-Shih Huang, Chun-Yuh Teng, Yi-Sheng Liou, Wu-Hsien Kuo, Wea-Lung Lin, Hai-I Huang, Jai-Nien Tung, Chih-Yang Huang, Jer-Yuh Liu, Wen-Hung Wang, Jin-Ming Hwang, Hsing-Chun Kuo
• Journal: Toxicology and applied pharmacology (Toxicol Appl Pharmacol) Vol. 255 Issue 3 Pg. 316-26 (Sep 15 2011) ISSN: 1096-0333 [Electronic] United States
• PMID: 21803068 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• Flavanones
• baicalein

Topics

• Animals
• Carcinoma, Hepatocellular (drug therapy, pathology)
• Cell Line, Tumor
• Cell Migration Inhibition (drug effects, physiology)
• Cell Movement (drug effects, physiology)
• Cell Proliferation (drug effects)
• Female
• Flavanones (pharmacology, therapeutic use)
• Humans
• Liver Neoplasms, Experimental (drug therapy, pathology)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasm Invasiveness (pathology, prevention & control)
• Random Allocation
• Xenograft Model Antitumor Assays