Antiproliferative and Anti-Invasive Effect of Piceatannol, a Polyphenol Present in Grapes and Wine, against Hepatoma AH109A Cells

Piceatannol is a stilbenoid, a metabolite of resveratrol found in red wine. Piceatannol and sera from rats orally given piceatannol were found to dose-dependently suppress both the proliferation and invasion of AH109A hepatoma cells in culture. Its antiproliferative effect was based on cell cycle arrest at lower concentration (25~50 μM) and on apoptosis induction at higher concentration (100 μM). Piceatannol suppressed reactive oxygen species-potentiated invasive capacity by scavenging the intracellular reactive oxygen species. These results suggest that piceatannol, unlike resveratrol, has a potential to suppress the hepatoma proliferation by inducing cell cycle arrest and apoptosis induction. They also suggest that the antioxidative property of piceatannol, like resveratrol, may be involved in its anti-invasive action. Subsequently, piceatannol was found to suppress the growth of solid tumor and metastasis in hepatoma-bearing rats. Thus, piceatannol may be a useful anticancer natural product

Hypoglycemic effect of resveratrol in type 2 diabetic model db/db mice and its actions in cultured L6 myotubes and RIN-5F pancreatic β-cells

Resveratrol, a phytoalexin present in the skin of grapes and red wine, has been demonstrated to possess a wide range of health promoting activities including anti-diabetic properties. In the present study, we investigated the effect of resveratrol in both type 2 diabetic mice and cell culture systems. In cultured L6 myotubes, we studied the effect of resveratrol on glucose uptake and translocation of glucose transporter 4 to plasma membrane from the aspects of insulin signaling and AMP-activated protein kinase signaling. In cultured RIN-5F cells, we examined whether resveratrol would protect the pancreas-derived β-cells from oxidative stress. Resveratrol significantly suppressed the elevation in the fasting blood glucose level and the serum triglyceride and lipid peroxide levels in db/db mice. Resveratrol stimulated glucose uptake and glucose transporter 4 translocation by activating both insulin signaling and AMP-activated protein kinase signaling. Moreover, resveratrol could protect pancreatic β-cells from advanced glycation end products-induced oxidative stress and apoptosis. From these results, resveratrol is suggested to show anti-diabetic effect by stimulating both insulin-dependent and -independent glucose uptake in muscles and by protecting pancreatic β-cells from advanced glycation end products-induced oxidative stress and apoptosis

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

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

Suppression of growth, migration and invasion of highly-metastatic human breast cancer cells by berbamine and its molecular mechanisms of action

<p>Abstract</p> <p>Background</p> <p>Breast cancer is the second leading cause of cancer related deaths among females worldwide. Berbamine (BER), a kind of bis-benzylisoquinoline alkaloid, has been used to treat clinical patients with inflammation and cancer for many years in China. The purpose of this study is to investigate the activity of BER against highly-metastatic human breast cancer and its molecular mechanisms of action.</p> <p>Results</p> <p>In our study, we found that BER inhibits growth of highly-metastatic human breast cancer cell lines MDA-MB-231 and MDA-MB-435S cells dose-dependently and time-dependently. The sera from BER-treated rats suppress the growth of MDA-MB-231 cells. BER shows synergistic effects with some existing anticancer agents such as trichostatin A (TSA, the histone deacetylase inhibitor), celecoxib (the inhibitor of COX-2), and carmofur against the growth of MDA-MB-231 cells. BER also displays the strong activity of inducing apoptosis in both estrogen receptor-negative MDA-MB-231 cells and estrogen receptor-alpha-positive MCF-7 breast cancer cells, but not in normal human mammary epithelial cell line MCF10A. BER down-regulates anti-apoptotic protein Bcl-2 levels and up-regulates pro-apoptotic protein Bax expressions in MDA-MB-231 and MDA-MB-435S cells. BER also has synergistic effects with anticancer agents trichostatin A, celecoxib and/or carmofur on reducing Bcl-2/Bax ratios and VEGF secretions in MDA-MB-231 cells. In addition, BER significantly suppresses cell migration and invasion, as well as decreases pro-MMP-9/pro-MMP-2 activation in breast cancer cells. Furthermore, BER suppresses Akt and nuclear factor <it>κ</it>B signaling by reducing the phosphorylation of c-Met and Akt, and inhibiting their downstream targets such as nuclear factor <it>κ</it>B p-65, Bcl-2/Bax, osteopontin, VEGF, MMP-9 and MMP-2 on protein and/or mRNA levels in breast cancer cells.</p> <p>Conclusion</p> <p>Our findings have showed that BER suppresses the growth, migration and invasion in highly-metastatic human breast cancer cells by possibly inhibiting Akt and NF-<it>κ</it>B signaling with their upstream target c-Met and downstream targets Bcl-2/Bax, osteopontin, VEGF, MMP-9 and MMP-2. BER has synergistic effects with anticancer agents trichostatin A, celecoxib and carmofur on inhibiting the growth of MDA-MB-231 cells and reducing the ratio of Bcl-2/Bax and/or VEGF expressions in the cancer cells. These findings suggest that BER may have the wide therapeutic and/or adjuvant therapeutic application in the treatment of human breast cancer and other cancers.</p

The Effect of Phytochemicals and Food Bioactive Compounds on Diabetes

There are three main types of diabetes, namely, type 1 diabetes, type 2 diabetes (T2D), and diabetes in pregnancy (gestational diabetes) [...

Hyperuricemia in type 2 diabetic model KK-Ay/Ta mice: a potent animal model with positive correlation between insulin resistance and plasma high uric acid levels

Abstract Objective Hyperuricemia is recognized as a main cause of gout. Accumulating clinical evidence suggests that hyperuricemia is strongly associated with insulin resistance and abnormal glucose metabolism. However, there seem no proper animal models for investigating such associations. Ideal animal model is considered to be hyperuricemic as well as diabetic. Selecting the KK-Ay/Ta mouse model, the relationship between hyperuricemia and insulin resistance has been studied to characterize such an animal model. Results Male type 2 diabetic KK-Ay/Ta and age-matched normal C57BL/6J mice were maintained on a basal 20% casein diet for 35 days. Food intake, body weight gain, levels of plasma uric acid, glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and triglyceride in KK-Ay/Ta mice were significantly higher than those in normal mice. Plasma uric acid levels showed significant positive correlations with plasma glucose, insulin, HOMA-IR and triglyceride levels. These results suggest that the KK-Ay/Ta mouse strain is useful for studies on correlation between hyperuricemia and insulin resistance, and for those on effects of foods and their components on the relations