Synthetic Cannabinoid Activity Against Colorectal Cancer Cells
Wesley M. Raup-Konsavage, Megan Johnson, Christopher A. Legare, Gregory S. Yochum, Daniel J. Morgan, and Kent E. Vrana
Introduction: Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide, and new therapeutic strategies are still required. Here we screened a synthetic cannabinoid library to identify compounds that uniformly reduce the viability of seven CRC cell lines.
Material and Methods: Seven distinct CRC cell lines were treated with 10 μM cannabinoid compounds (from a library of 370 molecules) for 48 h, and cell viability was subsequently measured with MTS assay. Dose–response curves were conducted for compounds that were found to reproducibly reduce cell viability of one or more cell lines.
Results: We identified 10 compounds from the library that were able to reduce cell viability of CRC cell lines (with an IC50 ≤ 30 μM). Of these compounds, seven were specific for CRC cells, and six were effective in all CRC cell lines tested. Treatment with traditional phytocannabinoids (THC or CBD) was either ineffective or much less potent and only partially efficacious. Treatment with antagonists for the known cannabinoid receptors (alone or in combination) failed to block the activity of the most potent of identified compounds.
Conclusion: We identified three families of cannabinoid compounds that reduce CRC cell viability through a noncanonical receptor mechanism. Future modification of these compounds may lead to the development of novel therapies to treat this disease.
Source : Journal Cannabis and Cannabinoid Research
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Identification of Synergistic Interaction Between Cannabis-Derived Compounds for Cytotoxic Activity in Colorectal Cancer Cell Lines and Colon Polyps That Induces Apoptosis-Related Cell Death and Distinct Gene Expression
Rameshprabu Nallathambi, Moran Mazuz, Dvory Namdar, Michal Shik, Diana Namintzer, Ajjampura C. Vinayaka, Aurel Ion,
Adi Faigenboim, Ahmad Nasser, Ido Laish, Fred M. Konikoff, and Hinanit Koltai
Introduction: Colorectal cancer remains the third most common cancer diagnosis and fourth leading cause of cancer-related mortality worldwide. Purified cannabinoids have been reported to prevent proliferation, metastasis, and induce apoptosis in a variety of cancer cell types. However, the active compounds from Cannabis sativa flowers and their interactions remain elusive.
Research Aim: This study was aimed to specify the cytotoxic effect of C. sativa-derived extracts on colon cancer cells and adenomatous polyps by identification of active compound(s) and characterization of their interaction.
Materials and Methods: Ethanol extracts of C. sativa were analyzed by high-performance liquid chromatography and gas chromatograph/mass spectrometry and their cytotoxic activity was determined using alamarBlue-based assay (Resazurin) and tetrazolium dye-based assay (XTT) on cancer and normal colon cell lines and on dysplastic adenomatous polyp cells. Annexin V Assay and fluorescence-activated cell sorting (FACS) were used to determine apoptosis and cell cycle, and RNA sequencing was used to determine gene expression.
Results: The unheated cannabis extracts (C2F), fraction 7 (F7), and fraction 3 (F3) had cytotoxic activity on colon cancer cells, but reduced activity on normal colon cell lines. Moreover, synergistic interaction was found between F7 and F3 and the latter contains mainly cannabigerolic acid. The F7 and F7+F3 cytotoxic activity involved cell apoptosis and cell cycle arrest in S or G0/G1 phases, respectively. RNA profiling identified 2283 differentially expressed genes in F7+F3 treatment, among them genes related to the Wnt signaling pathway and apoptosis-related genes. Moreover, F7, F3, and F7+F3 treatments induced cell death of polyp cells.
Conclusions:C. sativa compounds interact synergistically for cytotoxic activity against colon cancer cells and induce cell cycle arrest, apoptotic cell death, and distinct gene expression. F3, F7, and F7+F3 are also active on adenomatous polyps, suggesting possible future therapeutic value.
Source : Cannabis and Cannabinoid Research
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Alcohol consumption and survival of colorectal cancer patients: a population-based study from Germany
- Viola Walter3,*,
- Lina Jansen3,
- Alexis Ulrich8,
- Wilfried Roth4,9,
- Hendrik Bläker10,
- Jenny Chang-Claude5,
- Michael Hoffmeister3, and
- Hermann Brenner
Background: Studies on the association between alcohol consumption and colorectal cancer (CRC) prognosis have yielded inconsistent results.
Objective: The associations of lifetime and 1-y prediagnostic alcohol consumption with relevant prognostic outcomes were evaluated in a large population-based cohort of CRC patients.
Design: In 2003–2010, 3121 patients diagnosed with CRC were interviewed on sociodemographic and lifestyle factors, medication, and comorbidities. Cancer recurrence, vital status, and cause of death were documented for a median follow-up time of 4.8 y. With the use of Cox proportional hazard regression, associations between lifetime and recent alcohol consumption and overall, CRC-specific, recurrence-free, and disease-free survival were analyzed.
Results: In this patient cohort with a median age of 69 y at diagnosis, lifetime abstainers showed poorer overall [adjusted HR (aHR): 1.25; 95% CI: 1.03, 1.52] and CRC-specific (aHR: 1.37; 95% CI: 1.10, 1.70) survival than lifetime light drinkers (women: >0–12 g/d; men: >0–24 g/d). Lifetime heavy drinkers showed poorer overall (aHR: 1.37; 95% CI: 1.06, 1.78) and disease-free (aHR: 1.38; 95% CI: 1.09, 1.74) survival. Alcohol abstaining in the year before diagnosis was associated with poorer overall (aHR: 1.42; 95% CI: 1.20, 1.68), CRC-specific (aHR: 1.38; 95% CI: 1.13, 1.68), and disease-free (aHR: 1.23; 95% CI: 1.05, 1.44) survival. Lifetime abstainers with nonmetastatic disease showed poorer CRC-specific (aHR: 1.48; 95% CI: 1.10, 2.00) and recurrence-free (aHR: 1.32; 95% CI: 1.02, 1.70) survival. Wine abstaining but not beer or liquor abstaining was associated with poorer survival. Associations between alcohol consumption and prognosis varied according to presence of diabetes and age.
Conclusions: Prediagnostic alcohol abstaining and heavy drinking were associated with poorer survival after a CRC diagnosis than light drinking. The protective effects of light consumption might be restricted to wine, and associations might differ according to age and presence of diabetes mellitus.
Source : American Journal of Clinical Nutrition
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Vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting GAPDH
Jihye Yun1, Edouard Mullarky1,2, Changyuan Lu3, Kaitlyn N. Bosch1, Adam Kavalier3, Keith Rivera4, Jatin Roper5, Iok In Christine Chio4, Eugenia G. Giannopoulou6,*, Carlo Rago7, Ashlesha Muley1, John M. Asara8, Jihye Paik9,Olivier Elemento6, Zhengming Chen10, Darryl J. Pappin4, Lukas E. Dow1, Nickolas Papadopoulos7,Steven S. Gross3, Lewis C. Cantley1,†
More than half of human colorectal cancers (CRCs) carry either KRAS or BRAF mutations, and are often refractory to approved targeted therapies. We report that cultured CRC cells harboring KRAS or BRAFmutations are selectively killed when exposed to high levels of vitamin C. This effect is due to increased uptake of the oxidized form of vitamin C, dehydroascorbate (DHA), via the GLUT1 glucose transporter. Increased DHA uptake causes oxidative stress as intracellular DHA is reduced to vitamin C, depleting glutathione. Thus, ROS accumulates and inactivates glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Inhibiting GAPDH in highly glycolytic KRAS or BRAF mutant cells leads to an energetic crisis and cell death not seen in KRAS and BRAF wild-type cells. High-dose vitamin C impaired tumor growth in Apc/KrasG12Dmutant mice. These results provide a mechanistic rationale for exploring the therapeutic use of vitamin C for CRCs with KRAS or BRAF mutations.
Source : Scence
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Colon carcinogenesis is inhibited by the TRPM8 antagonist cannabigerol, a Cannabis-derived non-psychotropic cannabinoid
- Francesca Borrelli†¶,
- Ester Pagano†¶,
- Barbara Romano¶,
- Stefania Panzera,
- Francesco Maiello1,
- Diana Coppola1,
- Luciano De Petrocellis2,¶,
- Lorena Buono2,¶,
- Pierangelo Orlando3,¶§ and
- Angelo A. Izzo*,¶
Cannabigerol (CBG) is a safe non-psychotropic Cannabis-derived cannabinoid (CB), which interacts with specific targets involved in carcinogenesis. Specifically, CBG potently blocks transient receptor potential (TRP) M8 (TRPM8), activates TRPA1, TRPV1 and TRPV2 channels, blocks 5-hydroxytryptamine receptor 1A (5-HT1A) receptors and inhibits the reuptake of endocannabinoids. Here, we investigated whether CBG protects against colon tumourigenesis. Cell growth was evaluated in colorectal cancer (CRC) cells using the 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide and 3-amino-7-dimethylamino-2-methylphenazine hydrochloride assays; apoptosis was examined by histology and by assessing caspase 3/7 activity; reactive oxygen species (ROS) production by a fluorescent probe; CB receptors, TRP and CCAAT/enhancer-binding protein homologous protein (CHOP) messenger RNA (mRNA) expression were quantified by reverse transcription–polymerase chain reaction; small hairpin RNA-vector silencing of TRPM8 was performed by electroporation. The in vivoantineoplastic effect of CBG was assessed using mouse models of colon cancer. CRC cells expressed TRPM8, CB1, CB2, 5-HT1A receptors, TRPA1, TRPV1 and TRPV2 mRNA. CBG promoted apoptosis, stimulated ROS production, upregulated CHOP mRNA and reduced cell growth in CRC cells. CBG effect on cell growth was independent from TRPA1, TRPV1 and TRPV2 channels activation, was further increased by a CB2 receptor antagonist, and mimicked by other TRPM8 channel blockers but not by a 5-HT1A antagonist. Furthermore, the effect of CBG on cell growth and on CHOP mRNA expression was reduced in TRPM8 silenced cells. In vivo, CBG inhibited the growth of xenograft tumours as well as chemically induced colon carcinogenesis. CBG hampers colon cancer progression in vivo and selectively inhibits the growth of CRC cells, an effect shared by other TRPM8 antagonists. CBG should be considered translationally in CRC prevention and cure.
Source : Journal Carcinogenesis
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Melissa officinalis extract induces apoptosis and inhibits proliferation in colon cancer cells through formation of reactive oxygen species.
Purpose: Efficient strategies for the prevention of colon cancer are extensively being explored, including dietary intervention and the development of novel phytopharmaceuticals. Safe extracts of edible plants contain structurally diverse molecules that can effectively interfere with multi-factorial diseases such as colon cancer. In this study, we describe the antiproliferative and proapoptotic effects of ethanolic lemon balm (Melissa officinalis) leaves extract in human colon carcinoma cells. We further investigated the role of extra and intracellular reactive oxygen species (ROS).
Methods: Antitumor effects of lemon balm extract (LBE) were investigated in HT- 29 and T84 human colon carcinoma cells. Inhibition of proliferation was analyzed by DNA quantification. The causal cell cycle arrest was determined by flow cytometry of propidium iodide-stained cells and by immunoblotting of cell cycle regulator proteins. To investigate apoptosis, cleavage of caspases 3 and 7 was detected by immunoblotting and fluorescence microscopy. Phosphatidylserine externalization was measured by Annexin V assays. Mechanistic insights were gained by measurement of ROS using the indicator dyes CM-H2DCFDA and Cell ROX Green.
Results: After 3 and 4 days of treatment, LBE inhibited the proliferation of HT- 29 and T84 colon carcinoma cells with an inhibitory concentration ([IC.sub.50]) of 346 and 120 [micro]g/ml, respectively. Antiproliferative effects were associated with a G2/M cell cycle arrest and reduced protein expression of cyclin dependent kinases (CDK) 2, 4, 6, cyclin D3, and induced expression of cyclin-dependent kinase inhibitor 2C (p18) and 1A (p21). LBE (600 [micro]g/ml) induced cleavage of caspases 3 and 7 and phosphatidylserine externalization. LBE-induced apoptosis was further associated with formation of ROS, whereas quenching of ROS by antioxidants completely rescued the colon carcinoma cells from LBE-induced apoptosis.
Conclusions: Lemon balm (Melissa officinalis) extract inhibits the proliferation of colon carcinoma cells and induces apoptosis through formation of ROS. Taken together, LBE or subfractions thereof could be used for the prevention of colon cancer.
Source : Intl Journal of Phytotherapy and Phytopharmacology
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Oral milk thistle extract stops colorectal cancer stem cells from growing tumors
In results presented at the American Association for Cancer Research (AACR) Annual Meeting 2015, a University of Colorado Cancer Center study shows that orally administering the chemical silibinin, purified from milk thistle, slows the ability of colorectal cancer stem cells to grow the disease. When stem cells from tumors grown in silibinin-fed conditions were re-injected into new models, the cells failed to develop equally aggressive tumors even in the absence of silibinin.
“It’s very simple: tumors from mice that were initially fed silibinin had fewer cancer stem cells, were smaller, had lower metabolisms and showed decreased growth of new blood vessels. Importantly, when these cancer stem cells from tumors in mice fed silibinin were re-injected into new mice, we found these stem cells had lost their potential to repopulate even in the absence of silibinin exposure,” says Rajesh Agarwal, PhD, co-program leader of Cancer Prevention and Control at the CU Cancer Center and professor at the Skaggs School of Pharmacy and Pharmaceutical Sciences.
Silibinin is a non-toxic, potentially chemopreventive agent derived from milk thistle seeds. Results presented by Agarwal and colleagues at last year’s AACR Annual Meeting showed that, in cell cultures, silibinin affects cell signaling associated with the formation and survival of colorectal cancer stem cells. The current study extends this promising line of research into mouse models.
Specifically, the group used sorted colorectal cancer stem cells to grow tumors in mice that were either fed or not fed with silibinin. Tumor growth was measured by visible size, MRI scan and measurement of tumor metabolism (glucose use). These tumors cells either unsorted or sorted for cancer stem cells were then re-injected in mice to measure their growth pattern in next generations in the absence of silibinin feeding.
“We have been deeply involved in this line of research that extends from silibinin to its chemopreventive properties in colorectal cancer, and the current study takes another important step: we see both a likely chemopreventive and a therapeutic mechanism and the result of this mechanism in animal models,” says Sushil Kumar, PhD, postdoctoral fellow in the Agarwal Lab.
The group continues to investigate the molecular mechanisms, cell culture, and animal model effects of silibinin toward a likely human clinical trial of silibinin in cancer preventative and/or treatment settings.
Source : University of Colorado Cancer Center
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For Survivors of Colorectal Cancer, More Exercise, Less TV May Lower Risk of Death
“Turn off the TV and go outside and play” is an admonishment heard by many children—sage advice that seems to benefit adults as well. According to a new article in the Journal of Clinical Oncology (JCO), the simple recipe of “more exercise, less TV” might be particularly beneficial for survivors of colorectal cancer (CRC).
The study, “Pre- and Post-Diagnosis Physical Activity, Television Viewing, and Mortality Among Colorectal Cancer Patients in the NIH-AARP Diet and Health Study,” published online, ahead of print, December 8, 2014, asked how time devoted to exercising and watching TV— both before and after diagnosis— affected the risk of dying among survivors of colorectal cancer. To answer this question, the researchers used data from the NIH-AARP Diet and Health Study, which provided pre-diagnosis information on 3,797 survivors of CRC and post-diagnosis information on 1,759 survivors.
In summing up the findings of the study, first author Hannah Arem, PhD, MHS, of the National Cancer Institute, said, “The takeaway message from our study is that the colorectal cancer survivors who both watched less TV and did more exercise had the lowest mortality compared to those who watched more TV and did less exercise.”
More exercise associated with lower mortality risk
The study found that survivors of CRC who exercised seven hours or more per week before their diagnosis had a 20% lower risk of dying of any cause compared to survivors who did not exercise at all. Those who exercised seven hours or more per week after their diagnosis had a 31% lower risk of dying of any cause compared to survivors who did not exercise—a similar benefit was observed among survivors who exercised as little as four hours per week both before and after diagnosis. Exercising after diagnosis was associated with a reduced risk of death independent of whether or not the survivor exercised before diagnosis. On average, survivors’ reports on exercise were given four years after diagnosis.
Four to five hours of TV watching per day associated with greater mortality risk
The study also reported that survivors of CRC who watched more than five hours of TV per day before their diagnosis had a 22% increased risk of dying of any cause, compared to survivors who watched less than two hours per day. As far as TV watching after diagnosis, survivors who watched more than four hours of TV per day had a 25% increased mortality risk compared to survivors who watched less than two hours per day; however, this post-diagnosis difference was not statistically significant.
Colorectal Cancer Survivorship: an important public health issue
Only one previous study examined the association between sedentary activity and survivorship among survivors of CRC, and this current study is the first to look specifically at TV watching. Dr. Arem said that one of the reasons the researchers chose to focus on TV watching is that it is a behavior that can be modified with relative ease.
“TV watching is the most prevalent leisure time behavior, and it is an area where individuals can intervene,” said Dr. Arem. “It’s a lot harder to ask someone to change how they sit at work or which transportation mode they use. Asking people to reduce time in front of a TV is a public health message that can be put into action.”
According to Dr. Arem, identifying behaviors that can reduce the mortality risk among survivors of CRC is an important public health issue since the population of survivors numbers one million in the United States, and is growing.
“This is a population that deserves to have more research on their specific needs,” said Dr. Arem.
And as this new research in JCO suggests, one of those specific needs may be to leave the couch and take a walk outside.
“The findings in this study add another piece of evidence that for the more than one million survivors of colorectal cancer, even moderate exercise, such as walking four hours per week and keeping TV watching to two hours a day, might improve survival in this population.”
Source ASCO Connections
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Gut Microbes May Be a Risk Factor for Colorectal Cancer
—Findings have potential implications for prevention and treatment of the second leading cause of cancer death in the U.S.--
In one of the largest epidemiological studies of human gut bacteria and colorectal cancer ever conducted, a team of researchers at NYU Langone Medical Center has found a clear association between gut bacteria and colorectal cancer. The study, published today in the Journal of the National Cancer Institute, discovered that colorectal cancer patients had fewer beneficial bacteria and more harmful bacteria than people without the disease.
"Our findings are important because identification of these microbes may open the door for colorectal cancer prevention and treatment,” says Jiyoung Ahn, PhD, assistant professor of population health, and a member of NYU Cancer Institute, who led the study.
The human gut hosts thousands of bacteria, which play an important role in regulating food digestion and inflammation. Mounting evidence links gut microbes to colorectal cancer, a condition diagnosed in 143,000 people in the U.S. each year. The disease kills an estimated 51,000 Americans, second only to lung cancer. However, it is not well understood why colorectal cancer develops.
The researchers compared the DNA composition of intestinal microbes in the stool samples of 141 colorectal cancer patients and healthy volunteers. They found that samples from colorectal-cancer patients had larger populations of Fusobacteria than healthy volunteers. Fusobacteria commonly found in the mouth and gastrointestinal track, are associated with gut inflammation.
Moreover, case samples were more likely than the controls to be depleted of Clostridia, a class of beneficial gut bacteria that help digest dietary fiber and carbohydrates.
“Our next step is to study how diet and lifestyle factors modulate these gut bacteria associated with colorectal cancer. This may lead to ways to prevent this disease” says Dr. Ahn.
Source : Newswise
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Combination of Selenium and Green Tea Improves the Efficacy of Chemoprevention in a Rat Colorectal Cancer Model by Modulating Genetic and Epigenetic Biomarkers
Ying Hu mail, Graeme H. McIntosh, Richard K. Le Leu, Laura S. Nyskohus, Richard J. Woodman,Graeme P. Young
Dietary supplementation of selenium and green tea holds promise in cancer prevention. In this study, we evaluated the efficacies of selenium and green tea administered individually and in combination against colorectal cancer in an azoxymethane (AOM)-induced rat colonic carcinogenesis model and determined the underlying mechanisms of the protection. Four-week old Sprague-Dawley male rats were fed with diets containing 0.5% green tea extract, 1ppm selenium as selenium-enriched milk protein, or combination of 1ppm selenium and 0.5% green tea extract. Animals received 2 AOM (15 mg/kg) treatments to induce colonic oncogenesis. Rats were killed 8 or 30 wk later after the last AOM to examine the effect of dietary intervention on aberrant crypt foci (ACF) formation or tumor development. On sacrifice, colons were examined for ACF and tumors, the mRNA levels of SFRP5 and Cyclin D1, and the proteins levels of ß-catenin, COX-2, Ki-67, DNMT1 and acetyl histone H3. The combination of selenium and green tea resulted in a significant additive inhibition of large ACF formation, this effect was greater than either selenium or green tea alone, P<0.01; the combination also had a significant additive inhibition effect on all tumor endpoints, the effect of the combination diet on tumor incidence, multiplicity and size was greater than selenium or green tea alone, P<0.01. Rats fed the combination diet showed marked reduction of DNMT1 expression and induction of histone H3 acetylation, which were accompanied by restoration of SFRP5 mRNA in normal-appearing colonic crypts. The combination diet also significantly reduced ß-catenin nuclear translocation, Cyclin D1 expression and cell proliferation. These data show, for the first time, that combination of selenium and green tea is more effective in suppressing colorectal oncogenesis than either agent alone. The preventive effect is associated with regulation of genetic and epigenetic biomarkers implicated in colonic carcinogenesis.
Source : Plos One
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Model Selection Approach Suggests Causal Association between 25-Hydroxyvitamin D and Colorectal Cancer
Lina Zgaga equal contributor mail, Felix Agakov equal contributor, Evropi Theodoratou, Susan M. Farrington, Albert Tenesa, Malcolm G. Dunlop,Paul McKeigue,Harry Campbell
Introduction Vitamin D deficiency has been associated with increased risk of colorectal cancer (CRC), but causal relationship has not yet been confirmed. We investigate the direction of causation between vitamin D and CRC by extending the conventional approaches to allow pleiotropic relationships and by explicitly modelling unmeasured confounders.
Methods Plasma 25-hydroxyvitamin D (25-OHD), genetic variants associated with 25-OHD and CRC, and other relevant information was available for 2645 individuals (1057 CRC cases and 1588 controls) and included in the model. We investigate whether 25-OHD is likely to be causally associated with CRC, or vice versa, by selecting the best modelling hypothesis according to Bayesian predictive scores. We examine consistency for a range of prior assumptions.
Results Model comparison showed preference for the causal association between low 25-OHD and CRC over the reverse causal hypothesis. This was confirmed for posterior mean deviances obtained for both models (11.5 natural log units in favour of the causal model), and also for deviance information criteria (DIC) computed for a range of prior distributions. Overall, models ignoring hidden confounding or pleiotropy had significantly poorer DIC scores.
Conclusion Results suggest causal association between 25-OHD and colorectal cancer, and support the need for randomised clinical trials for further confirmations.
Source : PLOS One
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Ginger: Is it Ready for Prime Time?
Gary D. Stoner
On the basis of substantial preclinical data showing the preventive efficacy of ginger and its constituents in vitro and in animal models, as well as a phase I pilot trial indicating that ginger extract is well tolerated in humans, Citronberg and colleagues conducted a pilot trial of ginger extract (2 g/day for 28 days) on biomarkers of cell proliferation [human telomerase reverse transcriptase (hTERT), MIB-1], differentiation (p21waf1/cip1), and apoptosis (Bax, Bcl-2) in colonic mucosa from individuals at high-risk for colorectal cancer. Results from the trial suggest that ginger may reduce proliferation in normal-appearing colorectal epithelium and increase apoptosis relative to proliferation, especially in the differentiation zone of colon crypts. The authors suggest that these results support a larger study to confirm the pilot data. Before proceeding with a larger trial, however, it seems prudent to confirm ginger as a chemopreventive for colorectal cancer in animals, particularly when tested in postinitiation protocols and to identify reliable molecular biomarkers of effect that could be evaluated in clinical trials. Pharmacokinetic studies to examine the distribution and localization of ginger compounds and metabolites in the differentiation and proliferative zones of colonic crypts in animals and humans would also be informative. Finally, because the effects of ginger on normal colonic mucosa seem minimal, consideration should be given to the conduct of future trials in humans with premalignant colorectal disease.
Source : cancer Prevention Research
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Could Mistletoe Give the Kiss of Death to Cancer?
Mistletoe has become an important symbol of Christmas, but it also has the potential to play a vital role as an alternative therapy for sufferers of colon cancer.
At the University of Adelaide in Australia, scientists are interested in how the extract of mistletoe could either assist chemotherapy or act as an alternative to chemotherapy as a treatment for colon cancer.
Colon cancer is the second greatest cause of cancer death in the Western world. Mistletoe extract is already authorized for use by sufferers of colon cancer in Europe, but not in some countries such as Australia and the United States due to a lack of scientific testing.
For her Honours research project recently completed at the University of Adelaide, Health Sciences student Zahra Lotfollahi compared the effectiveness of three different types of mistletoe extract and chemotherapy on colon cancer cells. She also compared the impact of mistletoe extract and chemotherapy on healthy intestinal cells.
In her laboratory studies, she found that one of the mistletoe extracts -- from a species known as Fraxini (which grows on ash trees) -- was highly effective against colon cancer cells in cell culture and was gentler on healthy intestinal cells compared with chemotherapy.
Significantly, Fraxini extract was found to be more potent against cancer cells than the chemotherapy drug.
"This is an important result because we know that chemotherapy is effective at killing healthy cells as well as cancer cells. This can result in severe side effects for the patient, such as oral mucositis (ulcers in the mouth) and hair loss," Ms Lotfollahi says.
"Our laboratory studies have shown Fraxini mistletoe extract by itself to be highly effective at reducing the viability of colon cancer cells. At certain concentrations, Fraxini also increased the potency of chemotherapy against the cancer cells.
"Of the three extracts tested, and compared with chemotherapy, Fraxini was the only one that showed a reduced impact on healthy intestinal cells. This might mean that Fraxini is a potential candidate for increased toxicity against cancer, while also reducing potential side effects. However, more laboratory testing is needed to further validate this work," Ms Lotfollahi says.
"Mistletoe extract has been considered a viable alternative therapy overseas for many years, but it's important for us to understand the science behind it," says one of Ms Lotfollahi's supervisors, the University of Adelaide's Professor Gordon Howarth, a Cancer Council Senior Research Fellow.
"Although mistletoe grown on the ash tree was the most effective of the three extracts tested, there is a possibility that mistletoe grown on other, as yet untested, trees or plants could be even more effective.
"This is just the first important step in what we hope will lead to further research, and eventually clinical trials, of mistletoe extract in Australia," Professor Howarth says.
Source : Science Daily
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Magnesium intake and colorectal tumor risk: a case-control study and meta-analysis1,2,3,4
- Petra A Wark,
- Rosa Lau,
- Teresa Norat, and
- Ellen Kampman
Background: Dietary magnesium might be related to colorectal tumor risk through the pivotal roles of magnesium in cellular metabolism, insulin resistance, and systemic inflammation.
Objective: We evaluated the hypothesis of whether higher dietary magnesium intake is associated with reduced colorectal tumor risk.
Design: A case-control study on colorectal adenomas (768 cases; 709 polyp-free control subjects) and a meta-analysis of colorectal adenomas (3 case-control studies) and carcinomas (6 prospective cohort studies) were conducted. Dietary magnesium was estimated from food-frequency questionnaires in the case-control study and most studies in the meta-analyses. Data analysis comprised multiple logistic regression analysis (case-control study) and fixed- and random-effects meta-analyses.
Results: The case-control study showed a nonsignificant inverse association between dietary magnesium intake and risk of colorectal adenomas (OR for every 100-mg/d increase: 0.81; 95% CI: 0.62, 1.06). However, inverse associations were observed only in subjects with BMI (in kg/m2) ≥25, in subjects aged ≥55 y, and for advanced adenomas. Associations did not vary by the calcium-to-magnesium intake ratio. In the meta-analysis, every 100-mg/d increase in magnesium intake was associated with 13% lower risk of colorectal adenomas (OR: 0.87; 95% CI: 0.75, 1.00) and 12% lower risk of colorectal cancer (RR: 0.88; 95% CI: 0.81, 0.97).
Conclusions: Our findings support the hypothesis that higher intakes of dietary magnesium are associated with lower risk of colorectal tumors. The consumption of magnesium-rich foods may be a new avenue to explore further in the search for cancer-prevention strategies.
Source : The AMerican Journal of Clinical Nutrition
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Fed fiber, killer cells may ward off cancer
Fiber supplements may help the body’s own killer cells fight bacterial infection and reduce inflammation, greatly decreasing the risk of colon cancer.
Prebiotics are fiber supplements that serve as food for the trillions of tiny bacteria living in the gut. When taken, they can stimulate the growth of the “good” bacteria.
The evolution of prebiotic supplements—as well as probiotics, which are actual bacteria ingested into the system—provide new therapeutic targets for researchers and physicians.
In research published in the Journal of Nutrition, Michigan State University’s Jenifer Fenton reports that mice given the prebiotic galacto-oligosaccharide, or GOS, saw the severity of their colitis, which is one of the main forms of inflammatory bowel disease, significantly reduced.
In fact, the mice fed GOS—a synthetic compound that is known to stimulate beneficial bacteria and is found in foods such as biscuits and infant formula—saw a 50 percent reduction in colitis.
Research has shown certain types of foods and fibers can reduce colon cancer risk, says Fenton, who is part of the Department of Food Science and Human Nutrition.
“There is something unique about certain types of fibers, such as GOS, and how they alter cells and influence the immune system to change disease risk, either for the good or bad,” she says. “Our overall goal is to identify either dietary patterns or diet components to reduce inflammation and cancer risk.
“In this case, we used prebiotics to stimulate changes in bacteria in the gut that may have a beneficial impact on the colon.”
Fenton worked closely on the project with Elizabeth Gardner, who previously has looked at the impact diet plays in fighting off the flu.
In applying some of the lessons learned in those studies to mice with bacterially induced colitis, the researchers found mice given GOS had significantly less inflammation and fewer abnormal cells, two precursors for colon cancer.
It appeared, Fenton says, that the positive results were linked to the significant enhancement of the body’s own natural killer cells, found in the immune system and crucial in fighting off new infections in the body.
“Our results suggest GOS may be effective in reducing colitis severity by priming the innate immune system,” she says.
The next step is to verify how that mechanism works; finding that link could help researchers apply the lessons learned to other intestinal ailments.
Source : Futurity
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