Anti-invasive activity of α-tocopherol against hepatoma cells in culture via protein kinase C inhibition.

Effects of α-, ß-, γ- and δ-tocopherols on the proliferation and invasion of AH109A hepatoma cells and their modes of action were investigated. Four tocopherols inhibited the invasion as well as the proliferation of AH109A cells. Their inhibitory effects were more prominent on the invasion than on the proliferation. At 1 µM, α-tocopherol showed most potent anti-invasive activity without any influence on the proliferation. We have previously demonstrated that reactive oxygen species increase the invasion of AH109A cells. α-Tocopherol suppressed the reactive oxygen species-induced invasion but failed to suppress the reactive oxygen species-induced rises in intracellular peroxide level. GF 109203X, a protein kinase C inhibitor, decreased the invasive activity of AH109A cells. In contrast, phorbol-12-myristate-13-acetate, a protein kinase C activator, increased the invasive capacity of AH109A cells. α-Tocopherol suppressed the phorbol-12-myristate-13-acetate-induced increase in the invasion, and canceled the phorbol-12-myristate-13-acetate-induced rises in protein kinase C activity and phosphorylation of extracellular signal-regulated kinase. These results suggest that tocopherols, especially α-tocopherol, possess inhibitory effect more strongly on the invasion of AH109A cells than on the proliferation. They also suggest that the anti-invasive activity of α-tocopherol is raised through suppression of PKC/ERK signaling.

Anti-invasive activity of niacin and trigonelline against cancer cells.

The effects of niacin, namely, nicotinic acid and nicotinamide, and trigonelline on the proliferation and invasion of cancer cells were studied using a rat ascites hepatoma cell line of AH109A in culture. Niacin and trigonelline inhibited the invasion of hepatoma cells at concentrations of 2.5-40 microM without affecting proliferation. Hepatoma cells previously cultured with a reactive oxygen species (ROS)-generating system showed increased invasive activity. Niacin and trigonelline suppressed this ROS-potentiated invasive capacity through simultaneous treatment of AH109A cells with the ROS-generating system. The present study indicates for the first time the anti-invasive activities of niacin and trigonelline against cancer cells.

Inhibitory effect of ascorbic Acid on the proliferation and invasion of hepatoma cells in culture.

Effect of ascorbic acid (AsA) on the proliferation and invasion of rat ascites hepatoma AH109A cells was investigated by measuring [(3)H]thymidine incorporation into acid-insoluble fraction of the cells and by co-culturing the hepatoma cells with rat mesentery-derived mesothelial cells, respectively. AsA suppressed the invasion of AH109A cells in a dose-dependent manner at concentrations of 62.5-500 muM, while it inhibited the proliferation of the cells at higher concentrations of 250 and 500 muM. Hepatoma cells previously cultured with hypoxanthine (HX) and xanthine oxidase (XO) or with hydrogen peroxide showed increased invasive activities. AsA suppressed the reactive oxygen species-potentiated invasive capacity by simultaneously treating AH109A cells with AsA, HX and XO or with AsA and hydrogen peroxide. Furthermore, AsA reduced the intracellular peroxide levels in AH109A cells. These results suggest that the antioxidative property of AsA may be involved in its anti-invasive action on hepatoma cells.