[Show abstract][Hide abstract] ABSTRACT: Anthocyanins are dietary flavonoids, which can prevent carcinogen-induced colorectal cancer in rats. Here, the hypotheses were tested that Mirtoselect, an anthocyanin mixture from bilberry, or isolated cyanidin-3-glucoside (C3G), the most abundant anthocyanin in diet, interfere with intestinal adenoma formation in the Apc(Min) mouse, a genetic model of human familial adenomatous polyposis, and that consumption of C3G or Mirtoselect generates measurable levels of anthocyanins in the murine biophase. Apc(Min) mice ingested C3G or Mirtoselect at 0.03, 0.1 or 0.3% in the diet for 12 weeks, and intestinal adenomas were counted. Plasma, urine and intestinal mucosa were analyzed for presence of anthocyanins by high-pressure liquid chromatography with detection by UV spectrophotometry (520 nm) or tandem mass spectrometry (multiple reaction monitoring). Ingestion of either C3G or Mirtoselect reduced adenoma load dose-dependently. At the highest doses of C3G and Mirtoselect adenoma numbers were decreased by 45% (p < 0.001) or 30% (p < 0.05), respectively, compared to controls. Anthocyanins were found at the analytical detection limit in the plasma and at quantifiable levels in the intestinal mucosa and urine. Anthocyanin glucuronide and methyl metabolites were identified in intestine and urine. Total anthocyanin levels in mice on C3G or Mirtoselect were 43 ng and 8.1 microg/g tissue, respectively, in the intestinal mucosa, and 7.2 and 12.3 microg/ml in the urine. The efficacy of C3G and Mirtoselect in the Apc(Min) mouse renders the further development of anthocyanins as potential human colorectal cancer chemopreventive agents worthwhile.
International Journal of Cancer 12/2006; 119(9):2213-20. · 6.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: DMU-135 (3,4-Methylenedioxy-3',4',5'-trimethoxy chalcone) is a novel anticancer prodrug designed to be activated into a potent tyrosine kinase inhibitor by the tumour selective enzyme activity of the cytochrome P450 enzyme CYP1B1. CYP1B1 is selectively expressed in a wide variety of tumours including colon. The hypothesis was tested that DMU-135 would inhibit Apc(Min/+) mouse gastrointestinal adenoma formation. From 4-18 weeks of age animals received DMU-135 (0.2% w:w) in AIN93G diet. DMU-135 was well tolerated, induced no systemic side-effects and reduced adenoma multiplicity by 46 +/- 18.3% compared to controls (p < 0.001). Further characterisation of this promising chemopreventive agent is required.
Investigational New Drugs 12/2006; 24(6):459-64. · 3.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The flavone apigenin occurs in many leafy vegetables and fruits. It has been reported to have cancer chemopreventive efficacy in rodents. An HPLC method described previously for the determination of tricin, the dimethoxy cogener of apigenin, was modified and validated for measurement of apigenin in mouse tissues. Separation was carried out on a Hypersil-BDS C(18) column (4.6 x 250 mm) with an isocratic mobile phase of 55% methanol in 0.1 m ammonium acetate, pH 5.10, containing 0.27 mm disodium ethylenediamine tetraacetic acid. UV detection was at 336 nm, without interference from endogenous tissue compounds. The assay was linear in the range 25-400 ng/mL, 0.25-4 microg/mL and 2.5-40 microg/mL, with r(2) > 0.99 in all cases, for mouse plasma, liver and intestinal mucosa, respectively. Apigenin in mouse plasma, liver and intestinal mucosa was efficiently extracted with 0.1 m acetic acid in acetone. The assay recovery at low, medium and high concentrations was between 94.6 and 131.7% for all biomatrices, with a relative standard deviation of <10%. The lower limit of quantification for plasma was 25 ng/mL with a relative standard deviation of <15%. The method was used to measure the steady-phase apigenin levels in tissues of mice receiving apigenin in their diet.
[Show abstract][Hide abstract] ABSTRACT: Anthocyanins are potent antioxidants that may possess chronic disease preventive properties. Here, rapid, reliable, and reproducible solid-phase extraction, high-performance liquid chromatography (HPLC), and mass spectrometry techniques are described for the isolation, separation, and identification of anthocyanins in human plasma and urine. Recoveries of cyanidin-3-glucoside (C3G) were 91% from water, 71% from plasma, and 81% from urine. Intra- and interday variations for C3G extraction were 9 and 9.1% in plasma and 7.1 and 9.1% in urine and were less than 15% for all anthocyanins from a standardized bilberry extract (mirtoselect). Analysis of mirtoselect by HPLC with UV detection produced spectra with 15 peaks compatible with anthocyanin components found in mirtoselect within a total run time of 15 min. Chromatographic analysis of human urine obtained after an oral dose of mirtoselect yielded 19 anthocyanin peaks. Mass spectrometric analysis employing multiple reaction monitoring suggests the presence of unchanged anthocyanins and anthocyanidin glucuronide metabolites.
Journal of Agricultural and Food Chemistry 10/2006; 54(19):7009-13. · 3.11 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Trabectedin is a marine-derived cytoxic alkaloid which has shown promising antitumour activity in a variety of human malignancies including sarcoma. Fifty-four patients with advanced sarcoma (age 43 yrs, range 18-70), all pretreated with prior chemotherapy, were enrolled on a named individual basis for treatment with trabectedin. Diagnosis was adult soft tissue sarcoma (STS) in 46 patients, Ewing's family tumour (EFT) in 4, and osteosarcoma (OS) in 4. The initial 23 patients (total number of courses administered: 68) did not receive premedication prior to trabectedin, while the other 31 patients (total number of courses administered: 134) received premedication with dexamethasone 4 mg po bid 24 hours before therapy. Incidence of toxicity (grade 3-4), expressed as percentage of courses, was as follows: in patients without dexamethasone, elevation of transaminases 34%, neutropenia 24% and thrombocytopenia 25%; in patients with prior dexamethasone, elevation of transaminases 2%, neutropenia 2% and no thrombocytopenia. The median received dose intensity of trabectedin was superimposable in the two groups (404 microg and 400 microg per week, respectively), as well as progression-free survival (19% at 6 months). Among STS patients, 9% had objective responses. In this unselected patient series, premedication with dexamethasone strongly reduced drug-induced hepatotoxicity and myelosuppression.
European Journal of Cancer 08/2006; 42(10):1484-90. · 5.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Agents that prevent cancer, delay its onset, or revert premalignant conditions could have dramatic beneficial impacts on human health. Although there is an urgent need to develop cancer chemopreventive agents, researchers in the field suspect that this area of scientific endeavour in Europe leads a Cinderella existence, both in terms of perception of importance and research funding. In order to review current activities in this prevention field and to seek a consensus position, an exploratory workshop was held in September 2005 at the German Cancer Research Center (DKFZ) in Heidelberg, Germany, sponsored mainly by the European Science Foundation (ESF), and also supported by the European Association for Cancer Research (EACR) and the German Cancer Society (DKG). The 35 experts from European countries and the United States of America assessed state-of-the-art cancer chemoprevention research in Europe. The aims that the workshop organizers had pre-defined were: i) assessment of the usefulness of animal models for agent identification; ii) review of ongoing preclinical and clinical work on novel agents; iii) discussion of potential biomarkers predictive for cancer preventive efficacy; and finally iv) the potential role that European pharmaceutical industries could play in furthering chemopreventive agent development. Overall the workshop aimed at raising awareness among European clinical and laboratory researchers of the importance of the development of novel, efficacious and safe cancer preventive agents.
European Journal of Cancer 08/2006; 42(10):1338-43. · 5.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Oxidative stress is induced in the liver by application of the Pringle manoeuvre. Malondialdehyde is a carbonyl compound formed during lipid peroxidation and prostaglandin biosynthesis, which combines with DNA to form a number of adducts. Among them is the DNA adduct; 3-(2-deoxybeta-dierythropentafuranosyl) pyr [1, 2-alpha]-purin-10 (3H) one or M1G. This study was undertaken to determine the suitability of M1G as a novel marker of ischemia-reperfusion injury in the liver and its correlation with both the length of Pringle clamp application and the overall length of the operation.
Normal and colorectal liver metastatic tissues were obtained in 12 patients before and after application of the Pringle manoeuvre. All samples were snap-frozen in liquid nitrogen at -80 degree centigrade. DNA was extracted and M1G quantification was performed by immunoslotblot analysis.
M1G levels in normal liver tissue were 4.0+/-1.0 per 10(7) nucleotides before the Pringle manoeuvre and 7.4 +/-1.0 per 10(7) nucleotides after the Pringle manoeuvre (mean+/-standard deviation) (P<0.05 by ANOVA). M1G levels in malignant liver tissue were 2.5+/-1.4 per 10(7) nucleotides before the Pringle manoeuvre and 6.5+/-1.9 adducts per 10(7) nucleotides after the Pringle manoeuvre (P<0.05). Adduct levels in normal liver tissue showed a significant correlation with cumulative period of Pringle application.
This is the first time that the tissue levels of M1G before and after application of the Pringle manoeuvre have been studied. The results show that the Pringle manoeuvre exerts significant oxidative stress in human hepatocytes, which is Pringle-time dependent. The results highlight the potential for oxidative DNA adducts levels as a tool for measuring the severity of ischemia-reperfusion injury.
[Show abstract][Hide abstract] ABSTRACT: Silibinin, a flavonolignan from milk thistle, has intestinal cancer chemopreventive efficacy in rodents. It is a strong antioxidant and modulates the insulin-like growth factor (IGF) system by increasing circulating levels of IGF-binding protein 3 (IGFBP-3) and decreasing levels of IGF-I. Here, the hypothesis was tested that administration of oral silibinin generates agent levels in human blood and colorectal and hepatic tissues consistent with pharmacologic activity. Patients with confirmed colorectal adenocarcinoma received silibinin formulated with phosphatidylcholine (silipide) at dosages of 360, 720, or 1,440 mg silibinin daily for 7 days. Blood and biopsy samples of normal and malignant colorectum or liver were obtained before dosing, and blood and colorectal or hepatic tissues were collected at resection surgery after the final silipide dose. Levels of silibinin were quantified by high-pressure liquid chromatography-UV, and plasma metabolites were identified by liquid chromatography-mass spectrometry. Blood levels of IGFBP-3, IGF-I, and the oxidative DNA damage pyrimidopurinone adduct of deoxyguanosine (M1dG) were determined. Repeated administration of silipide was safe and achieved levels of silibinin of 0.3 to 4 micromol/L in the plasma, 0.3 to 2.5 nmol/g tissue in the liver, and 20 to 141 nmol/g tissue in colorectal tissue. Silibinin monoglucuronide, silibinin diglucuronide, silibinin monosulfate, and silibinin glucuronide sulfate were identified in the plasma. Intervention with silipide did not affect circulating levels of IGFBP-3, IGF-I, or M1dG. The high silibinin levels achieved in the human colorectal mucosa after consumption of safe silibinin doses support its further exploration as a potential human colorectal cancer chemopreventive agent.
Clinical Cancer Research 06/2006; 12(9):2944-50. · 7.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The natural polphenol, curcumin, retards the growth of intestinal adenomas in the Apc(Min+) mouse model of human familial adenomatous polyposis. In other preclinical models, curcumin downregulates the transcription of the enzyme cyclooxygenase-2 (COX-2) and decreases levels of two oxidative DNA adducts, the pyrimidopurinone adduct of deoxyguanosine (M1dG) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG). We have studied COX-2 protein expression and oxidative DNA adduct levels in intestinal adenoma tissue from Apc(Min+) mice to try and differentiate between curcumin's direct pharmacodynamic effects and indirect effects via its inhibition of adenoma growth. Mice received dietary curcumin (0.2%) for 4 or 14 weeks. COX-2 protein, M1dG and 8-oxo-dG levels were measured by Western blot, immunochemical assay and liquid chromatography-mass spectrometry, respectively. In control Apc(Min+) mice, the levels of all three indices measured in adenoma tissue were significantly higher than levels in normal mucosa. Lifetime administration of curcumin reduced COX-2 expression by 66% (P = 0.01), 8-oxo-dG levels by 24% (P < 0.05) and M1dG levels by 39% (P < 0.005). Short-term feeding did not affect total adenoma number or COX-2 expression, but decreased M1dG levels by 43% (P < 0.01). COX-2 protein levels related to adenoma size. These results demonstrate the utility of measuring these oxidative DNA adduct levels to show direct antioxidant effects of dietary curcumin. The effects of long-term dietary curcumin on COX-2 protein levels appear to reflect retardation of adenoma development.
European Journal of Cancer 02/2006; 42(3):415-21. · 5.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Therapeutic regulation of PPARdelta activity using selective agonists has been proposed for various disorders. However, the consequences of altered peroxisome proliferator-activated receptor delta (PPARdelta) activity in the context of intestinal tumourigenesis remain somewhat unclear. Contradictory evidence suggesting PPARdelta either attenuates or potentiates intestinal neoplasia. To further investigate the PPARdelta dependency of intestinal tumourigenesis, we have analysed the consequences of PPARdelta deficiency upon intestinal neoplasia occurring in mice with impaired mismatch DNA repair.
Mice deficient for both PPARdelta and the mismatch repair gene Mlh1 were produced and the incidence and severity of intestinal neoplasia recorded.
No significant differences between the control genotypes and the double mutant genotypes were recorded indicating that deficiency of PPARdelta does not modify impaired mismatch repair induced neoplasia.
In contrast with the previously observed acceleration of intestinal neoplasia in the context of the ApcMin/+ mouse, PPARdelta deficiency does not alter the phenotype of mismatch repair deficiency. This data supports the notion that PPARdelta is not required for adenoma formation and indicate that any pro-tumourigenic effect of PPARdelta inactivation may be highly context dependent.
[Show abstract][Hide abstract] ABSTRACT: Naturally occurring flavonoids such as quercetin and genistein possess cancer chemopreventive properties in experimental models. However, adverse effects such as their mutagenicity confound their potential clinical usefulness. Furthermore in leukaemia cells some flavonoids cleave the breakpoint cluster region of the mixed lineage leukaemia (MLL) gene as a consequence of inhibition of topoisomerase II. The choice of flavonoids to be developed as cancer chemopreventive agents depends crucially on their safety. Here, we explored safety aspects of the novel flavone tricin, a constituent of rice bran and other grass species, which has recently been found to interfere with murine gastrointestinal carcinogenesis.
Evidence of pathological or morphological changes in liver, lung, heart, spleen, kidney, adrenal gland, pancreas or thymus tissues was studied in mice which received tricin, genistein or quercetin 1,000 mg/kg daily by the oral route on five consecutive days. The ability of tricin (50 microM) to cleave the MLL gene was studied in human leukaemia cells by Southern blotting, and its effect on human topoisomerase II activity was investigated in incubations with supercoiled DNA. The mutagenicity of tricin was assessed in the Salmonella/Escherichia coli assay, and its clastogenicity was adjudged by chromosomal aberrations in Chinese hamster ovary cells and occurrence of micronuclei in bone marrow erythrocytes in Swiss-Webster mice.
Neither tricin, quercetin, or genistein caused pathological or morphological changes in any of the murine tissues studied. Tricin (50 microM) failed to cause MLL gene breakage, and it inhibited topoisomerase II only at 500 microM, but not at 10, 50 or 100 microM. Tricin lacked genotoxic properties in the systems studied here.
The results tentatively suggest that tricin may be considered safe enough for clinical development as a cancer chemopreventive agent.
Cancer Chemotherapy and Pharmacology 02/2006; 57(1):1-6. · 2.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To study the biological effects of quercetin, authentic products of quercetin metabolism are required as standards. The synthesis of quercetin sulfate standards is thus described. Quercetin was reacted with a 10-fold molar excess of sulfur trioxide-N-triethylamine, and the products were analyzed by HPLC and mass spectrometry. Four monosulfates and three disulfates were identified, and structural inferences were drawn by 1H NMR spectrometry of HPLC peak isolates. Analysis of the urine of rats that had received quercetin (1.9 g/kg po) yielded a single peak, which by comparison with the products of the reaction between quercetin and sulfur trioxide-N-triethylamine was identified as quercetin 3'-O-sulfate.
[Show abstract][Hide abstract] ABSTRACT: A lot of information has been gathered on cellular mechanisms by which chemopreventive phytochemicals, such as curcumin (a spice in curry) or epigallocatechin gallate (extracted from tea), interfere with carcinogenesis. A comparison of this knowledge with what we know about molecularly targeted chemotherapeutic agents suggests that it might be worthwhile to investigate the usefulness of such phytochemicals in the treatment of established malignant diseases. Phytochemicals use a plethora of antisurvival mechanisms, boost the host's anti-inflammatory defence, and sensitise malignant cells to cytotoxic agents. The restricted systemic availability of agents such as curcumin and epigallocatechin gallate, needs to be taken into account if they are to be developed as cochemotherapeutic drugs.
The Lancet Oncology 12/2005; 6(11):899-904. · 25.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The concept of delaying or preventing epithelial transformation remains a viable and attainable goal for the future. Drug-based strategies for chemoprevention of the future may predominantly rely upon targeted therapies with tolerable but defined toxicities for treatment of individuals diagnosed with intraepithelial neoplasias. Foods, diet manipulation strategies, or nutraceuticals may be more appropriate to delay or prevent carcinogenesis progression in healthy populations with genetic or epidemiologic evidence of risk for future transformation.
British Journal of Cancer 11/2005; 93(7):735-9. · 5.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Curcumin is a polyphenol derived from the herbal remedy and dietary spice turmeric. It possesses diverse anti-inflammatory and anti-cancer properties following oral or topical administration. Apart from curcumin's potent antioxidant capacity at neutral and acidic pH, its mechanisms of action include inhibition of several cell signalling pathways at multiple levels, effects on cellular enzymes such as cyclooxygenase and glutathione S-transferases, immuno-modulation and effects on angiogenesis and cell-cell adhesion. Curcumin's ability to affect gene transcription and to induce apoptosis in preclinical models is likely to be of particular relevance to cancer chemoprevention and chemotherapy in patients. Although curcumin's low systemic bioavailability following oral dosing may limit access of sufficient concentrations for pharmacological effect in certain tissues, the attainment of biologically active levels in the gastrointestinal tract has been demonstrated in animals and humans. Sufficient data currently exist to advocate phase II clinical evaluation of oral curcumin in patients with invasive malignancy or pre-invasive lesions of the gastrointestinal tract, particularly the colon and rectum.
European Journal of Cancer 10/2005; 41(13):1955-68. · 5.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Consumption of fruits and berries has been associated with decreased risk of developing cancer. The most abundant flavonoid constituents of fruits and berries are anthocyans (i.e. anthocyanins, glycosides, and their aglycons, anthocyanidins) that cause intense colouration. In this review, we describe epidemiological evidence hinting at the cancer preventive activity of anthocyan-containing foods in humans, results of chemoprevention studies in rodent models with anthocyans or anthocyan-containing fruit/vegetable extracts, and pharmacological properties of anthocyans. Anthocyanidins have been shown to inhibit malignant cell survival and confound many oncogenic signalling events in the 10(-6)-10(-4) M concentration range. Studies of the pharmacokinetics of anthocyanins after their consumption as single agents, anthocyanin mixtures or berry extracts suggest that anthocyanins reach levels of 10(-8)-10(-7) M in human blood. It is unclear whether such concentrations are sufficient to explain anticarcinogenic effects, and whether anthocyanins exert chemopreventive efficacy themselves, or if they need to undergo hydrolysis to their aglyconic counterparts. The currently available literature provides tantalising hints of the potential usefulness of anthocyans or anthocyan mixtures as cancer chemopreventive interventions. Nevertheless further studies are necessary to help adjudge the propitiousness of their clinical development.
European Journal of Cancer 10/2005; 41(13):1931-40. · 5.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: While brown rice is a staple dietary constituent in Asia, rice consumed in the Western world is generally white, obtained from brown rice by removal of the bran. Rice bran contains the flavone tricin, which has been shown to inhibit colon cancer cell growth. We tested the hypothesis that tricin interferes with adenoma formation in the Apc(Min) mouse. Mice received tricin (0.2%) in their American Institute of Nutrition 93G diet throughout their postweaning life span (4-18 weeks). Consumption of tricin reduced numbers of intestinal adenomas by 33% (P < 0.05) compared with mice on control diet. We explored whether tricin may exert its effect via inhibition of cyclooxygenase (COX) enzymes. Its effect on COX activity was assessed in purified enzyme preparations in vitro and its ability to reduce prostaglandin E(2) (PGE(2)) levels in human colon-derived human colon epithelial cell (HCEC) and HCA-7 cells in vitro and in Apc(Min) mice in vivo. Tricin inhibited activity of purified COX-1 and COX-2 enzyme preparations with IC(50) values of approximately 1 micromol/L. At 5 micromol/L, it reduced PGE(2) production in HCEC or HCA-7 cells by 36% (P < 0.01) and 35% (P < 0.05), respectively. COX-2 expression was reduced by tricin weakly in HCEC and unaffected in HCA-7 cells. PGE(2) levels in the small intestinal mucosa and blood of Apc(Min) mice that had received tricin were reduced by 34% (P < 0.01) and 40% (P < 0.05), respectively, compared with control mice. The results suggest that tricin should be further evaluated as a putative colorectal cancer chemopreventive agent.
Molecular Cancer Therapeutics 09/2005; 4(9):1287-92. · 5.60 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: AHPLC method developed and validated for the determination of tricin in human plasma published previously was cross-validated to allow measurement of the flavone tricin in plasma and tissues of mice. Blank samples of plasma, liver or intestinal mucosa were spiked with tricin at 0.5--4.0, 1.0--8.0 and 5.0--40 microg/mL, respectively. These tricin concentration ranges covered the tricin levels achieved in the mouse tissues in the dose-escalating experiments. Analysis afforded linear calibration curves with regression coefficients of >0.99. Endogenous compounds did not interfere with tricin detection when the detection wavelength was set at 355 nm, the maximum absorbance of tricin. Accuracy and precision were <15% for all concentrations in all matrices except for the precision at the lower limit of quantification (0.5 microg/mL) in mouse plasma, which was 18.4%. Consumption of diet mixed with tricin at 0.05, 0.2 or 0.5% for one week furnished steady-state levels in plasma, liver and small intestine in the 1--3 x 10(-7), 4--22 x 10(-7) and 3--46 x 10(-5) m ranges, respectively.
[Show abstract][Hide abstract] ABSTRACT: Naturally occurring molecules with putative cancer chemopreventive properties such as the phytoalexin resveratrol (3,5,4'-trihydroxystilbene) are lead molecules that guide the design of novel agents with improved pharmacologic properties. The synthetic resveratrol analog 3,4,5,4'-tetramethoxystilbene (DMU-212) has been shown to possess stronger antiproliferative properties in human colon cancer cells than resveratrol. We tested the hypothesis that DMU-212 is also a more potent inhibitor of adenoma development in the Apc(Min+) mouse, a model of human intestinal carcinogenesis. Apc(Min+) mice received either stilbene derivative with the diet (0.2%), and adenomas were counted after experiments were terminated. Resveratrol and DMU-212 decreased adenoma load by 27% and 24%, respectively, compared to untreated controls. Cyclooxygenase (COX) enzymes are important mechanistic targets of resveratrol, and we investigated whether DMU-212 interferes with the expression and activity of COX in human colon cells. Incubation of HCA-7 cancer cells for 24-96 hr with either stilbene derivative (1-50 microM) decreased prostaglandin E-2 (PGE-2) production, but only resveratrol decreased COX-2 protein expression. In mice, which received either stilbene derivative (0.2%) for 3 weeks with their diet, PGE-2 levels in the intestinal mucosa were reduced by between 45% and 62% compared to mice on control diet. While resveratrol inhibited enzyme activity in purified COX preparations, DMU-212 failed to do so. The PGE-2 decrease seen with DMU-212 in cells and in vivo is probably mediated via its metabolites. The results suggest that alteration of the resveratrol molecule to generate DMU-212 does not abrogate its ability to decrease adenoma number in Apc(Min+) mice or to interfere with PGE-2 generation in cells.
International Journal of Cancer 07/2005; 115(2):194-201. · 6.20 Impact Factor