Department of Applied Biological Chemistry, Graduate School of Agriculture, Tokyo University of Agriculture and Technology, Fuchu, Tokyo 183-8509, Japan.
J Clin Biochem Nutr. 2011 May;48(3):251-7. doi: 10.3164/jcbn.10-117. Epub 2011 Apr 13.
Effects of α-, β-, 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.
研究了四种生育酚（α-、β-、γ-和 δ-生育酚）对 AH109A 肝癌细胞增殖和侵袭的影响及其作用方式。四种生育酚均抑制 AH109A 细胞的侵袭和增殖。它们对侵袭的抑制作用比对增殖的抑制作用更为明显。在 1μM 时，α-生育酚表现出最强的抗侵袭活性，而对增殖没有影响。我们之前已经证明，活性氧会增加 AH109A 细胞的侵袭。α-生育酚抑制活性氧诱导的侵袭，但未能抑制活性氧诱导的细胞内过氧化物水平升高。蛋白激酶 C 抑制剂 GF 109203X 降低了 AH109A 细胞的侵袭活性。相反，蛋白激酶 C 激活剂十四烷酰佛波醇-12-醋酸酯增加了 AH109A 细胞的侵袭能力。α-生育酚抑制十四烷酰佛波醇-12-醋酸酯诱导的侵袭增加，并取消了十四烷酰佛波醇-12-醋酸酯诱导的蛋白激酶 C 活性和细胞外信号调节激酶磷酸化的增加。这些结果表明，生育酚，特别是α-生育酚，对 AH109A 细胞的侵袭具有比增殖更强的抑制作用。它们还表明，α-生育酚的抗侵袭活性通过抑制 PKC/ERK 信号通路而提高。
