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Chemopreventive Properties (chemopreventive + property)
Selected AbstractsIn vitro evaluation of the chemoprotective action mechanisms of leontopodic acid against aflatoxin B1 and deoxynivalenol-induced cell damageJOURNAL OF APPLIED TOXICOLOGY, Issue 1 2009Stefano Costa Abstract Several in vitro studies showed that free radical scavengers possess chemopreventive properties against mycotoxin-induced cell damage which are at least partially associated with the induction of phase II detoxifying enzymes and antioxidant enzymes like glutathione S -transferase (GST) and glutathione peroxidase (GPx). The aim of this project was to study the chemopreventive effects of leontopodic acid (LA), a potent natural occurring free radical scavenger isolated from the aerial parts of Leontopodium alpinum. Different mycotoxins were evaluated in two different cell lines on the basis of their specific toxicity: aflatoxin B1 (AFB1) on HepG2 cells and deoxynivalenol (DON) on U937 cells. Cell viability and reactive oxygen species concentration were determined, and the effects of pre-treatment with LA on these parameters were investigated together with the GST and GPx activity as well as the concentration of reduced glutathione. The results show that LA protects U937 cells from DON-induced cell damage but not HepG2 cells from AFB1. Moreover LA is able to enhance GPx activity in U937, but not GST activity in HepG2. We hypothesize that the increase in detoxifying enzymes is probably the main mechanism of antioxidant mediated chemoprevention. Copyright © 2008 John Wiley & Sons, Ltd. [source] Antiproliferative, cytotoxic and antitumour activity of coumarins isolated from Calophyllum brasilienseJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 5 2007César Ruiz-Marcial Among the eight Calophyllum species found on the American continent, Calophyllum brasiliense is the most widely distributed. Chemical analysis of this species has shown the presence of xanthones with cancer chemopreventive properties and antifungal activity. Recently, three new coumarins with antineoplastic properties have been found. In this study, we have evaluated the biological effects of the antiproliferative activity of coumarins isolated from C. brasiliense on the survival, cell cycle and apoptosis of cells in-vitro and their antitumour effects in mice. The cytological study showed that coumarins from C. brasiliense reduce the survival of BMK cells (baby mouse kidney cells) by inducing apoptosis and, to a lesser degree, necrosis. The cell cycle was arrested in S-phase and the division of BMK cells was inhibited. Coumarins had caused a reduction of experimental tumours in 83% of animals by the end of the treatment. Therefore, coumarins have the potential to be used alone or in combination with other antineoplastic drugs, and they might increase the effectiveness of other treatments for cancer. [source] Inhibitory effect of apigenin on benzo(a)pyrene-mediated genotoxicity in Swiss albino miceJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 12 2006Tajdar Husain Khan Apigenin, a bioflavonoid, is abundantly present in fruits and vegetables and possesses potential chemopreventive properties against a wide variety of chronic diseases. In this study we investigated the anti-genotoxic effects of apigenin against a known genotoxicant, benzo(a)pyrene (B(a)P) (125 mg kg,1 orally) toxicity in Swiss albino mice. B(a)P administration led to induction of cytochrome P-450 (CYP), aryl hydrocarbon hydroxylase (AHH) and DNA strand breaks (P < 0.001), which was suppressed by apigenin (2.5 and 5 mg kg,1 orally) dose dependently (P < 0.001). B(a)P-induced depletion in the level of reduced glutathione (GSH), quinone reductase (QR) and glutathione-S-transferase (GST) was also shown to be restored by apigenin pre-treatment (P < 0.001). A simultaneous significant and dose-dependent reduction was noted in DNA strand breaks and in-vivo DNA damage (P < 0.001), which gives some insight into restoration of DNA integrity in modulator groups. These results strongly support the protective nature of apigenin against B(a)P-induced toxicity. [source] Systematic review: molecular chemoprevention of colorectal malignancy by mesalazineALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2010A. LYAKHOVICH Summary Background, Mesalazine (mesalamine) (5-ASA) is considered an anti-inflammatory drug for the treatment of inflammatory bowel disease. It is well tolerated by most patients and induces mucosal healing specifically in ulcerative colitis. Besides its anti-inflammatory properties, 5-ASA has been studied for cancer inhibitory activities as it seems to reduce colorectal cancer incidence in patients using this drug for long periods of time. However, detailed molecular mechanisms of drug action are vague. Aims, To evaluate known molecular mechanisms of 5-ASA on chemoprevention of colorectal malignancy. Methods, Systematic review with search terms ,5 aminosalicylic acid, mesalazine, 5-ASA, mesalazine, molecular mechanisms, chemoprevention' between 2006 and August 2009. Results, A total of 48 studies were retrieved that link 5-ASA chemopreventive properties to five distinct pathways. These include interference with cell cycle progression (12 references), scavenging of reactive oxygen- or nitrogen-derived metabolites (16 references), TNF-,/TGF-ß signalling (11 references), WNT/,-catenin signalling (5 references) and anti-bacterial properties (4 references). Conclusions, In the recent years, a large amount of molecular data has accumulated supporting the notion that 5-ASA biological effects interfere with colorectal cancer development. These molecular pathways are of special interest in the search for 5-ASA's molecular target(s) and development of novel chemopreventive compounds. Aliment Pharmacol Ther,31, 202,209 [source] Evaluation of chemopreventive action of Ginsenoside Rp1BIOFACTORS, Issue 1 2006Ashok Kumar Abstract We evaluated the chemopreventive properties of Ginsenoside Rp1 on 7,12-Dimethyl benz (a) anthracene (DMBA) skin papillomagenesis in Swiss albino mice. A significant reduction in values of tumor incidence, tumor burden, and cumulative number of papilloma was observed in mice treated orally with Ginsenoside Rp1 continuously at pre-, peri- and post-initiational stages of papillomagenesis as compared to the control group. Chemopreventive potential of Ginsenoside Rp1 was also observed on the skin metabolizing enzymes in Swiss albino mice. Ginsenoside Rp1 produced a significant elevation in the skin microsomal cytochrome p-450 and cytochrome b5, glutathione S-transferase (GST), reduced glutathione (GSH), glutathione peroxidase (GPX), glutathione reductase (GR), DT-diaphorase, superoxide dismutase (SOD) and catalase levels in the group of mice treated with Ginsenoside Rp1 for seven consecutive days. However, there was significant decrease in lipid peroxidation (LPO) level in Ginsenoside Rp1 treated group. [source] Pitavastatin inhibits azoxymethane-induced colonic preneoplastic lesions in C57BL/KsJ- db/db obese miceCANCER SCIENCE, Issue 7 2010Yoichi Yasuda Obesity and related metabolic abnormalities are risk factors for colorectal cancer. A state of chronic inflammation and adipocytokine imbalance may play a role in colorectal carcinogenesis. Statins, which are commonly used for the treatment of hyperlipidemia, are known to possess anti-inflammatory effects. Statins also exert chemopreventive properties against various cancers. The present study examined the effects of pitavastatin, a recently developed lipophilic statin, on the development of azoxymethane (AOM)-initiated colonic premalignant lesions in C57BL/KsJ- db/db (db/db) obese mice. Male db/db mice were administrated weekly subcutaneous injections of AOM (15 mg/kg body weight) for 4 weeks and then were subsequently fed a diet containing 1 ppm or 10 ppm pitavastatin for 8 weeks. Feeding with either dose of pitavastatin significantly reduced the number of colonic premalignant lesions, ,-catenin accumulated crypts, by inhibiting proliferation and the surrounding inflammation. Pitavastatin increased the serum levels of adiponectin while conversely decreasing the serum levels of total cholesterol, tumor necrosis factor-, (TNF-,), interleukin (IL)-6, IL-18, and leptin. Pitavastatin also caused a significant increase in the expression of phosphorylated form of the AMP-activated kinase (AMPK) protein on the colonic mucosa of AOM-treated mice. In addition, the expression levels of TNF-,, IL-6, IL-18, and COX-2 mRNAs on the colonic mucosa of AOM-treated mice were decreased by treatment with this agent. These findings suggest that pitavastatin attenuates chronic inflammation and improves the imbalance of adipocytokines, both of which are caused by the presence of excess adipose tissues, thereby preventing the development of colonic premalignancies in an obesity-related colon cancer model. Therefore, some types of statins, including pitavastatin, may be a useful chemoprevention modality for colon cancer in obese individuals. (Cancer Sci 2010) [source] Targeting the development of resveratrol as a chemopreventive agent,DRUG DEVELOPMENT RESEARCH, Issue 6 2010Nian-Guang Li Abstract Tumor development consists of several separate, but closely linked, stages: tumor initiation, promotion, and progression. This long and complex process provides opportunities for intervention both in preventing cancer initiation and in treating the neoplasm during its premalignant stages. Resveratrol, a polyphenolic compound found in many plant species, including grapes, peanuts, and various herbs, has recently been investigated intensely for its cancer chemopreventive property. The present work is an overview of the chemopreventive mechanisms of resveratrol in anti-initiation, anti-promotion, and anti-progression. These, together with the low toxicity of resveratrol, suggest promise for novel chemopreventive agents. However, the low bioavailability and rapid clearance of resveratrol from the circulation require the design of new resveratrol-like chemopreventive agents, the structural modifications and the structure,activity relationship of which are also discussed in this review. Drug Dev Res 71:335,350, 2010. © 2010 Wiley-Liss, Inc. [source] Cell death induction by isothiocyanates and their underlying molecular mechanismsBIOFACTORS, Issue 2 2006Yoshimasa Nakamura Abstract An important and promising group of compounds that have a chemopreventive property are organosulfur compounds, such as isothiocyanates (ITCs). In recent years, it has been shown that ITCs induce apoptosis in various cancer cell lines and experimental rodents. During the course of apoptosis induction by ITC, multiple signal-transduction pathways and apoptosis intermediates are modulated. We have also clarified the molecular mechanism underlying the relationship between cell cycle arrest and apoptosis induced by benzyl isothiocyanate (BITC), a major ITC compound isolated from papaya. The exposure of cells to BITC resulted in the inhibition of the G2/M progression that coincided with not only the up-regulated expression of the G2/M cell cycle arrest-regulating genes but also the apoptosis induction. The experiment using the phase-specific synchronized cells demonstrated that the G2/M phase-arrested cells are more sensitive to undergoing apoptotic stimulation by BITC than the cells in other phases. We identified the phosphorylated Bcl-2 as a key molecule linking the p38 MAPK-dependent cell cycle arrest with the JNK activation by BITC. We also found that BITC induced the cytotoxic effect more preferentially in the proliferating normal human colon epithelial cells than in the quiescent cells. Conversely, treatment with an excessive concentration of BITC resulted in necrotic cell death without DNA ladder formation. This review addresses the biological impact of cell death induction by BITC as well as other ITCs and the involved signal transduction pathways. [source] | ||||||||||