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Chemopreventive Efficacy (chemopreventive + efficacy)
Selected AbstractsAntiangiogenetic Effects of 4 Varieties of Grapes,In VitroJOURNAL OF FOOD SCIENCE, Issue 6 2010Ming Liu Abstract:, The purpose of this study was to investigate the inhibitory effects of grapes on the human umbilical vein endothelial (HUVE) cells' capillary tube formation and matrix metalloproteinase-2 (MMP-2) expression secreted into the medium. Four different grape varieties (Concord, Niagara, Chardonnay, and Pinot Noir) were extracted using 80% acetone and the extracts were stored at ,80 °C. The total amount of phenolics and flavonoids for each of the 4 grape varieties were determined by spectrophotometry. Grape extracts were co-cultured with HUVE cells on Matrigel and inhibitory effects on tube formation were observed under a microscope. The inhibitory effects of grape extracts on MMP-2 expression were examined by zymogram. All 4 grape varieties inhibited the tube formation of HUVE cells in a dose-dependent manner on Matrigel. Except for Chardonnay, the other 3 grape varieties completely inhibited secretion of MMP-2 at 20 mg/mL. There was a significant positive relationship between the total phenolics and flavonoids and antiangiogenetic activities. The grapes tested have the potential to inhibit angiogenesis mainly by their phenolics and flavonoids contents, which partly contribute to their cancer chemopreventive efficacy. [source] Mesalazine inhibits the , -catenin signalling pathway acting through the upregulation of ,-protocadherin gene in colo-rectal cancer cellsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2010S. PARENTI Summary Background, Several reports indicate that mesalazine (5-aminosalicylic acid, 5-ASA) is a promising candidate for the chemoprevention of colo-rectal cancer because of its ability to reach the purpose avoiding the unwanted side effects usually associated with prolonged administration of nonsteroidal anti-inflammatory drugs. This activity of 5-ASA is probably the consequence of a number of effects determined on colo-rectal cancer cells, consisting of reduced proliferation, increased apoptosis and activation of cell cycle checkpoints and DNA repair processes. A recent observation has suggested that inhibition of ,-catenin signalling could induce these cellular effects. Aim, To characterize better the capacity of 5-ASA to inhibit the ,-catenin signalling pathway. Methods, Genes belonging to the ,-catenin signalling pathway were analysed in colo-rectal cancer cell lines treated with 5-ASA using a combination of laboratory assays that are able to detect their phenotypic expression and functional activity. Results, The results obtained indicated that 5-ASA induces the expression of a protein called ,-protocadherin that belongs to the cadherin superfamily and is able to sequester ,-catenin on the plasmatic membrane of treated cells hampering its function. Conclusion, These findings suggest that ,-protocadherin might be employed as a biological marker to monitor the chemopreventive efficacy of 5-ASA. [source] Dietary-feeding of grape seed extract prevents azoxymethane-induced colonic aberrant crypt foci formation in fischer 344 ratsMOLECULAR CARCINOGENESIS, Issue 7 2010Balaiya Velmurugan Abstract Chemoprevention by dietary agents/supplements has emerged as a novel approach to control various malignancies, including colorectal cancer (CRC). This study assessed dietary grape seed extract (GSE) effectiveness in preventing azoxymethane (AOM)-induced aberrant crypt foci (ACF) formation and associated mechanisms in Fischer 344 rats. Six-week-old rats were injected with AOM, and fed control diet or the one supplemented with 0.25% or 0.5% (w/w) GSE in pre- and post-AOM or only post-AOM experimental protocols. At 16,wk of age, rats were sacrificed and colons were evaluated for ACF formation followed by cell proliferation, apoptosis, and molecular analyses by immunohistochemistry. GSE-feeding caused strong chemopreventive efficacy against AOM-induced ACF formation in terms of up to 60% (P,<,0.001) reduction in number of ACF and 66% (P,<,0.001) reduction in crypt multiplicity. Mechanistic studies showed that GSE-feeding inhibited AOM-induced cell proliferation but enhanced apoptosis in colon including ACF, together with a strong decrease in cyclin D1, COX-2, iNOS, and survivin levels. Additional studies showed that GSE-feeding also decreased AOM-caused increase in ,-catenin and NF-,B levels in colon tissues. Compared to control animals, GSE alone treatment did not show any considerable change in these biological and molecular events in colon, and was nontoxic. Together, these findings show the chemopreventive efficacy of GSE against the early steps of colon carcinogenesis in rats via likely targeting of ,-catenin and NF-,B signaling, and suggest its potential usefulness for the prevention of human CRC. © 2010 Wiley-Liss, Inc. [source] Antiangiogenic and Chemopreventive Activities of Celecoxib in Oral Carcinoma Cell,,THE LARYNGOSCOPE, Issue 5 2002Zhi Wang MD Abstract Objectives Chemoprevention is a promising strategy to inhibit carcinoma before invasive tumors develop, but a new molecular target is desirable. Celecoxib is a newly developed cyclo-oxygenase (COX)-2 inhibitor with significantly less toxicity. The study was conducted to determine whether celecoxib is effective and safe in prevention of oral cancer. The antiangiogenic activity of celecoxib was studied to explore the potential mechanism involved. Study Design Randomized animal study. Methods The study consisted of two phases. In the phase 1, 10 mice were used to determine the efficacy and safety of celecoxib with intradermal inoculation with oral carcinoma cells. The 10 mice were equally divided into two groups 5 mice (30 inoculated sites) in each group to receive 1,500 parts per million (ppm) celecoxib mixed in with the diet or to eat a normal diet, respectively, for 21 days. In phase 2, 10 more mice were inoculated to determine the effect of celecoxib on angiogenesis. Five mice received 3,000 ppm celecoxib in the diet, with the other five mice as control animals. The antiangiogenic activity was evaluated by comparing the density of newly growing microvessels after the inoculation. Results The results indicated that celecoxib significantly delayed cell growth and reduced tumor volume. There was statistical significance in the quantity of new vasculature in the tumor sites between the two groups. No toxic effect was found by means of measurement of body weight loss and microscopic dissection of organs. Conclusions The study provided the first evidence to show the chemopreventive efficacy of celecoxib on oral cancer in a nude mouse model. Clinical trials are warranted to determine the efficacy in humans. [source] Tephrosia purpurea Ameliorates N-Diethylnitrosamine and Potassium Bromate-Mediated Renal Oxidative Stress and Toxicity in Wistar RatsBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 6 2001Naghma Khan 1999). The present study was designed to investigate a chemopreventive efficacy of T. purpurea against N-diethylnitrosamine-initiated and potassium bromate-mediated oxidative stress and toxicity in rat kidney. A single intraperitoneal dose of N-diethylnitrosamine (200 mg/kg body weight) one hr prior to the dose of KBrO3 (125 mg/kg body weight) increases microsomal lipid peroxidation and the activity of xanthine oxidase and decreases the activities of renal antioxidant enzymes viz., catalase, glutathione peroxidase, glutathione reductase and glucose-6-phosphate dehydrogenase, phase II metabolizing enzymes such as glutathione-S-transferase and quinone reductase and causes depletion in the level of renal glutathione content. A sharp increase in blood urea nitrogen and serum creatinine has also been observed. Prophylactic treatment of rats with T. purpurea at doses of 5 mg/kg body weight and 10 mg/kg body weight prevented N-diethylnitrosamine-initiated and KBrO3 promoted renal oxidative stress and toxicity. The susceptibility of renal microsomal membrane for iron ascorbate-induced lipid peroxidation and xanthine oxidase activities were significantly reduced (P<0.01). The depleted levels of glutathione, the inhibited activities of antioxidant enzymes, phase II metabolizing enzymes and the enhanced levels of serum creatinine and blood urea nitrogen were recovered to a significant level (P<0.01). All the antioxidant enzymes were recovered dose-dependently. Our data indicate that T. purpurea besides a skin antioxidant can be a potent chemopreventive agent against renal oxidative stress and carcinogenesis induced by N-diethylnitrosamine and KBrO3. [source] | ||||||||||