Many cancers contain cell subpopulations that display characteristics of stem cells. These cells are characterised by their ability to self-renew, form differentiated progeny and develop resistance to chemotherapeutic strategies. Cancer stem cells may utilise many of the same signalling pathways as normal stem cells including Wnt, Notch and Hedgehog. The dietary agent curcumin exerts a plethora of anti-carcinogenic effects both in vitro and in vivo, and can also inhibit many of the signalling pathways associated with stem cell biology. Emerging evidence suggests that curcumin can exert its anti-carcinogenic activity via targeting cancer stem cells through the disruption of stem cell signalling pathways. In this review we summarise the ability of curcumin to interfere with signalling pathways Wnt, Hedgehog, Notch, Signal Transducers and Activator (STAT) and interleukin-8, and report curcumin-induced changes in function and properties of cancer stem cells. We present evidence that the effects of curcumin on cancer stem cells mediate, or contribute to, its anti-carcinogenic activity.
There is strong epidemiological evidence indicating that consumption by humans of whole-grain foods including rice bran may be associated with a low incidence of cancer, especially in the colorectum. Molecular processes associated with cancer development may be retarded by fibre consumption. Consequently intervention with dietary fibre might be suitable as a cancer chemoprevention strategy in high-risk populations. Here we searched for putative molecular mechanism-based efficacy biomarkers of rice fibre consumption in the plasma of mice characterised by a genetic propensity to develop gastrointestinal adenomas. The hypothesis was tested that metabolic and proteomic changes in blood reflect the chemopreventive activity of rice bran. Methods and Results:ApcMin mice received diet supplemented with rice bran at 5, 15 and 30%. Blood and tissue samples were taken. Plasma was subjected to mass spectrometry-based proteomic and metabolic profiling analyses as well as assessment of haematocrit values. Gastrointestinal tracts were removed and adenomas were counted and their size was measured so that total tumour burden could be calculated. The hypothesis was tested that metabolic and proteomic changes in blood reflect chemopreventive activity. Conclusion:Rice bran consumption reduced adenoma burden and number in a dose-related fashion when compared to controls. Metabolic profiling data demonstrated strong clustering of the groups indicating that metabolic pathways are perturbed. Proteomic analysis identified adiponectin as a molecule that was significantly altered, which may play a role in tumour suppression. IntroductionEpidemiological evidence suggests that human consumption of whole-grain foods is associated with a low incidence of cancer, especially in the colorectum [1]. Rice is the staple food of over half the world's population. Whilst the unpolished brown (bran-containing) variety possesses special dietary importance in Asia, rice consumed in the Western world is generally white, obtained from brown rice by bran removal. Dietary differences such as this may explain why the incidence of certain cancers, including those in the colorectum, is much lower in Asia than in the West [2]. A stabilised rice bran preparation containing 25-35% fibre, when added at 30% to the diet, interfered with adenoma development in the Apc Min min mouse, a model of colorectal carcinogenesis [3]. These mice possess a heritable Apc gene mutation which is responsible for adenoma formation [4]. Importantly, the fibre content was pivotal for the adenoma retarding activity of the rice bran, as a rice bran formulation from which most of the fibre had been removed was devoid of efficacy in this model [3]. Three types of mechanism have been proffered by which dietary fibre including that from rice is thought to potentially interfere with colorectal carcinogenesis. Firstly, fibre is thought to exert 'physical' effects such as increasing faecal bulk, hastening faecal transit and binding potentially cocarcinogenic bile salts. Secondly, fibre may benef...
3',4',5'-Trimethoxyflavonol (TMFol) is a synthetic flavonol with preclinical cancer chemopreventive properties. The hypothesis was tested that, in mice, p.o. administration of TMFol results in measureable levels of the parent in target tissues. A single oral dose (240 mg/kg) was administered to mice (n = 4 per time point) with time points ranging from 5 to 1440 min. TMFol and its metabolites were identified and quantitated in all tissues by high-performance liquid chromatography (HPLC). Plasma levels of TMFol were at the limit of quantification or below, although metabolites were identified. Peak levels of TMFol in the gastrointestinal tract and the prostate averaged 1671 ± 265 µg/g (5.3 µmol/g) and 6.0 ± 1.6 µg/g (18.4 nmol/g), and occurred 20 and 360 min post-dose, respectively. The area under the tissue concentration-time curve (AUC) for TMFol was greater than those of the metabolites, indicating that TMFol is relatively metabolically stable. Micromolar TMFol levels are easily achieved in the prostate and gastrointestinal tract, suggesting that TMFol might exert chemopreventive efficacy at these tissue sites. Further investigations are warranted to elucidate the potential chemopreventive potency of TMFol.
Pancreatic cancer is a disease with a significantly poor prognosis. Despite modern advances in other medical, surgical, and oncologic therapy, the outcome from pancreatic cancer has improved little over the last 40 years. To improve the management of this difficult disease, trials investigating the use of dietary and parenteral fish oils rich in omega-3 (ω-3) fatty acids, exhibiting proven anti-inflammatory and anticarcinogenic properties, have revealed favorable results in pancreatic cancers. Proteomics is the large-scale study of proteins that attempts to characterize the complete set of proteins encoded by the genome of an organism and that, with the use of sensitive mass spectrometric-based techniques, has allowed high-throughput analysis of the proteome to aid identification of putative biomarkers pertinent to given disease states. These biomarkers provide useful insight into potentially discovering new markers for early detection or elucidating the efficacy of treatment on pancreatic cancers. Here, our review identifies potential proteomic-based biomarkers in pancreatic cancer relating to apoptosis, cell proliferation, angiogenesis, and metabolic regulation in clinical studies. We also reviewed proteomic biomarkers from the administration of ω-3 fatty acids that act on similar anticarcinogenic pathways as above and reflect that proteomic studies on the effect of ω-3 fatty acids in pancreatic cancer will yield favorable results.
Angiosarcomas of the small intestine are rare and present non-specifically. They usually manifest with abdominal discomfort, altered bowel habits, anaemia and gastrointestinal bleeding. Diagnosis is often challenging and occurs at an advanced tumour stage. We describe a case of a terminal ileum angiosarcoma masquerading as an appendiceal abscess, and discuss salient clinicopathological features in diagnosing and managing this disease.
Consumption of dietary bran has been considered to be beneficial to health. It has also been linked to a lower risk of developing malignancies, most notably, colorectal cancer. Rice bran (containing 23-35% dietary fiber) at 30% in the diet interfered with adenoma development in the ApcMin mouse, a preclinical model of colorectal cancer (Verschoyle et al., Br J Cancer 2007). Here we used a high fiber rice bran extract (Nutracea, USA), with a fiber content of 40-50% to explore whether an increase in fiber imparts higher efficacy in the ApcMin mouse. The bran was mixed in with the diet at three concentrations: 5, 15 and 30% (n=19-22 per group) and administered to ApcMin mice from 4 weeks of age until termination of study at 16 weeks. Adenoma numbers were reduced by 12, 26, 74 % and adenoma burden by 30, 26 and 84 %, respectively, in the treatment groups in comparison to control mice, with reduction being significant only at the highest dose (p<0.05). The high fiber rice bran seems to be more efficacious than the rice bran used in the previous study in which 30% rice bran reduced adenoma numbers by 51% (Verschoyle et al., Br J Cancer 2007). Plasma samples from each experimental group were collected and undergo proteomic analysis using liquid chromatography-mass spectrometry to identify potential biomarkers of efficacy. This study highlights the potential health benefit of high-fiber rice bran, but further investigations are warranted to better understand the role of fiber in colorectal cancer prevention. Citation Information: Cancer Prev Res 2010;3(12 Suppl):A98.
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