Resveratrol And VDR

Resveratrol is purported to have a number of health benefits; this paper explains one possible mechanism of action, abstract:

The 1,25-dihydroxyvitamin D3 (1,25D) hormone is derived from vitamin D generated in skin or obtained from the diet, and binds to and activates the vitamin D receptor (VDR) in target tissues including kidney, colon/small intestine, and bone/muscle. We tested resveratrol for its ability to modulate VDR signaling, using vitamin D responsive element (VDRE) and mammalian 2-hybrid (M2H) transcriptional system technology. Via VDRE-based assays in kidney, colon and myoblast cells, VDR-mediated transcription was activated by resveratrol, and a cooperative effect on transactivation was observed with resveratrol plus 1,25D. The M2H assay revealed a modest, resveratrol-induced dimerization of VDR with its retinoid X receptor (RXR) heteropartner. Cells treated with both resveratrol and 1,25D displayed synergistic stimulation of VDR-RXR heterodimerization, while resveratrol antagonized rexinoid-mediated RXR-RXR homodimerization. Increased transactivation in response to resveratrol was also observed with a subset of other nuclear receptors and their respective cognate responsive elements. Evaluation of wild-type versus a ligand-binding domain mutant VDR revealed that hormone-responsiveness to 1,25D was severely depressed, while the response to resveratrol was only moderately attenuated. Moreover, radiolabeled 1,25D-displacement assays demonstrated an increase in VDR-bound 1,25D in the presence of resveratrol. Thus, resveratrol may affect VDR and other nuclear receptors indirectly, likely via the ability of resveratrol to: (1) potentiate 1,25D binding to VDR; (2) activate RXR; and/or (3) stimulate SIRT1, an enzyme known to deacetylate nuclear receptors. The results of this study elucidate a possible pathway for crosstalk between two nutritionally derived lipids, vitamin D and resveratrol, both of which converge on VDR signaling.

Vitamin D and vitamin D signaling continuously proves to be extremely important for human health and disease prevention.

Coffee And Cancer Risk

Here is a paper on coffee consumption and cancer risk from several years ago,  Bottom like is that there doesn't seem to be a big effect either way; coffee can cause decreased risk for some cancers, but possibly increased risk for childhood leukemia with maternal coffee drinking during pregnancy. The data are "limited and inconsistent" in some cases; overall it seems like a "wash" based on these findings, no big effect. Abstract:

We reviewed available evidence on coffee drinking and the risk of all cancers and selected cancers updated to May 2016. Coffee consumption is not associated with overall cancer risk. A meta-analysis reported a pooled relative risk (RR) for an increment of 1 cup of coffee/day of 1.00 [95% confidence interval (CI): 0.99-1.01] for all cancers. Coffee drinking is associated with a reduced risk of liver cancer. A meta-analysis of cohort studies found an RR for an increment of consumption of 1 cup/day of 0.85 (95% CI: 0.81-0.90) for liver cancer and a favorable effect on liver enzymes and cirrhosis. Another meta-analysis showed an inverse relation for endometrial cancer risk, with an RR of 0.92 (95% CI: 0.88-0.96) for an increment of 1 cup/day. A possible decreased risk was found in some studies for oral/pharyngeal cancer and for advanced prostate cancer. Although data are mixed, overall, there seems to be some favorable effect of coffee drinking on colorectal cancer in case-control studies, in the absence of a consistent relation in cohort studies. For bladder cancer, the results are not consistent; however, any possible direct association is not dose and duration related, and might depend on a residual confounding effect of smoking. A few studies suggest an increased risk of childhood leukemia after maternal coffee drinking during pregnancy, but data are limited and inconsistent. Although the results of studies are mixed, the overall evidence suggests no association of coffee intake with cancers of the stomach, pancreas, lung, breast, ovary, and prostate overall. Data are limited, with RR close to unity for other neoplasms, including those of the esophagus, small intestine, gallbladder and biliary tract, skin, kidney, brain, thyroid, as well as for soft tissue sarcoma and lymphohematopoietic cancer.

I don't drink coffee myself, but based on these data overall it seems not do any harm taking all risks together - although pregnant women may want to ask their doctor about the risk in that specific case.

Warburg Effect And Some Possible Cancer Treatments

The Warburg effect is important in cancer, since cancer cells rely more heavily than do normal cells on glycolysis for energy production.  This may point at therapies targeting this effect for patient benefit.  A paper is here, abstract:

As stated by Otto Warburg nearly a century ago, cancer is a metabolic disease, a fermentation caused by malfunctioning mitochondria, resulting in increased anabolism and decreased catabolism. Treatment should, therefore, aim at restoring the energy yield. To decrease anabolism, glucose uptake should be reduced (ketogenic diet). To increase catabolism, the oxidative phosphorylation should be restored. Treatment with a combination of α-lipoic acid and hydroxycitrate has been shown to be effective in multiple animal models. This treatment, in combination with conventional chemotherapy, has yielded extremely encouraging results in glioblastoma, brain metastasis and lung cancer. Randomized trials are necessary to confirm these preliminary data. The major limitation is the fact that the combination of α-lipoic acid and hydroxycitrate can only be effective if the mitochondria are still present and/or functional. That may not be the case in the most aggressive tumors. The increased intracellular alkalosis is a strong mitogenic signal, which bypasses most inhibitory signals. Concomitant correction of this alkalosis may be a very effective treatment in case of mitochondrial failure.

Note that a ketogenic diet is considered one mechanism whereby the Warburg effect can be leveraged for anti-cancer treatment.

Vitamin D Against Colon Cancer

Roles of vitamin D in colon cancer prevention, abstract:

Colorectal cancer (CRC) is the neoplasia that is most frequently associated with vitamin D deficiency in epidemiological and observational studies in terms of incidence and mortality. Many mechanistic studies show that the active vitamin D metabolite (1α,25-dihydroxyvitamin D3 or calcitriol) inhibits proliferation and promotes epithelial differentiation of human colon carcinoma cell lines that express vitamin D receptor (VDR) via the regulation of a high number of genes. A key action underlining this effect is the multilevel inhibition of the Wnt/β-catenin signaling pathway, whose abnormal activation in colon epithelial cells initiates and promotes CRC. Recently, our group has shown that calcitriol modulates gene expression and inhibits protumoral properties of patient-derived colon cancer-associated fibroblasts (CAFs). Accordingly, high VDR expression in tumor stromal fibroblasts is associated with longer survival of CRC patients. Moreover, many types of immune cells express VDR and are regulated by calcitriol, which probably contributes to its action against CRC. Given the role attributed to the intestinal microbiota in CRC and the finding that it is altered by vitamin D deficiency, an indirect antitumoral effect of calcitriol is also plausible at this level. In summary, calcitriol has an array of potential protective effects against CRC by acting on carcinoma cells, CAFs, immune cells and probably also the gut microbiota.

Mushrooms Against Cancer

Factors from edible and medicinal mushrooms seem to have anti-cancer properties.  These sort of food-based therapies need to be studied better.  Abstract:

Cancer is the leading cause of morbidity and mortality around the globe. For certain types of cancer, chemotherapy drugs have been extensively used for treatment. However, severe side effects and the development of resistance are the drawbacks of these agents. Therefore, development of new agents with no or minimal side effects is of utmost importance. In this regard, natural compounds are well recognized as drugs in several human ailments, including cancer. One class of fungi, "mushrooms," contains numerous compounds that exhibit interesting biological activities, including antitumor activity. Many researchers, including our own group, are focusing on the anticancer potential of different mushrooms and the underlying molecular mechanism behind their action. The aim of this review is to discuss PI3K/AKT, Wnt-CTNNB1, and NF-κB signaling pathways, the occurrence of genetic alterations in them, the association of these aberrations with different human cancers and how different nodes of these pathways are targeted by various substances of mushroom origin. We have given evidence to propose the therapeutic attributes and possible mode of molecular actions of various mushroom-originated compounds. However, anticancer effects were typically demonstrated in in vitro and in vivo models and very limited number of studies have been conducted in the human population. It is our belief that this review will help the research community in designing concrete preclinical and clinical studies to test the anticancer potential of mushroom-originated compounds on different cancers harboring particular genetic alteration(s).

Dietary Influences On The Plasma Membrane: Cancer Implications

Diet can affect the cell plasma membrane and hence decrease caner risk, through modulation of cell signaling. Abstract:

The cell plasma membrane serves as a nexus integrating extra- and intracellular components, which together enable many of the fundamental cellular signaling processes that sustain life. In order to perform this key function, plasma membrane components assemble into well-defined domains exhibiting distinct biochemical and biophysical properties that modulate various signaling events. Dysregulation of these highly dynamic membrane domains can promote oncogenic signaling. Recently, it has been demonstrated that select membrane-targeted dietary bioactives (MTDBs) have the ability to remodel plasma membrane domains and subsequently reduce cancer risk. In this review, we focus on the importance of plasma membrane domain structural and signaling functionalities as well as how loss of membrane homeostasis can drive aberrant signaling. Additionally, we discuss the intricacies associated with the investigation of these membrane domain features and their associations with cancer biology. Lastly, we describe the current literature focusing on MTDBs, including mechanisms of chemoprevention and therapeutics in order to establish a functional link between these membrane-altering biomolecules, tuning of plasma membrane hierarchal organization, and their implications in cancer prevention.

Natural Product Polyphenols Against Cancer

Natural product polyphenols that can be obtained through diet can have anti-cancer properties, particularly with respect to cancer driven by chronic inflammation.  Modulation of signaling pathways and transcription factors may be involved in this anti-cancer effect. Abstract:

Inflammation is one of the major causative factor of cancer and chronic inflammation is involved in all the major steps of cancer initiation, progression metastasis and drug resistance. The molecular mechanism of inflammation driven cancer is the complex interplay between oncogenic and tumor suppressive transcription factors which include FOXM1, NF-kB, STAT3,Wnt/β- Catenin, HIF-1α,NRF2, androgen and estrogen receptors. Several products derived from natural sources modulate the expression and activity of multiple transcription factors in various tumor models as evident from studies conducted in cell lines, pre-clinical models and clinical samples. Further combination of these natural products along with currently approved cancer therapies added an additional advantage and they considered as promising targets for prevention and treatment of inflammation and cancer. In this review we discuss the application of multi-targeting natural products by analyzing the literature and future directions for their plausible applications in drug discovery.

Legumes And Colorectal Adenoma Risk

An unsurprising finding is that legume consumption is associated with deceased risk for colorectal adenoma.  More investigations are required because such “meta-analysis” can have confounding variables.  Still, the conclusion is consistent with all else we know about dietary recommendations regarding colorectal cancer prevention. Prevent the adenoma (poly), prevent the carcinoma (cancer). Fiber helps.  Abstract:

Background

The anticancer effects of legumes have been explored extensively, but evidence from epidemiologic studies on colorectal adenoma is controversial. We performed a meta-analysis to assess these issues.

Methods

A systemic search of several databases was conducted for relevant studies evaluating the relationship between legume intake and adenoma risk, with no language restriction, from January 1, 1966, to April 1, 2013.

Results

Three cohort and eleven case control studies with 8,380 cases and a total of 101,856 participants were included in the analysis; the pooled odds ratio (95% confidence interval) for the highest vs. lowest consumption categories was 0.83 (0.75–0.93), with moderate level of heterogeneity (I2 = 25.9% and P = 0.146) based on a random effects model. A decreased risk of adenoma was also observed in most of our subgroup meta-analyses.

Conclusions

Higher intake of legumes significantly reduced the risk of colorectal adenoma in our meta-analysis. Nevertheless, due to possible confounders and bias, further investigations are warranted to confirm this relationship.

Western Diet And Inflammation

A Western diet can not only promote cancer in mice, it also causes inflammation, and even after the mice are switched back to their normal diet, myeloid cells show enhanced immune response.  This change seems dependent on the product of the NLRP3 gene.  Thus, the high fat, calorie-dense Western diet can contribute to long-term, pro-inflammatory, negative alterations in the immune system and this likely is relevant for humans as well as mice.

Long-term epigenetic reprogramming of innate immune cells in response to microbes, also termed "trained immunity," causes prolonged altered cellular functionality to protect from secondary infections. Here, we investigated whether sterile triggers of inflammation induce trained immunity and thereby influence innate immune responses. Western diet (WD) feeding of Ldlr-/- mice induced systemic inflammation, which was undetectable in serum soon after mice were shifted back to a chow diet (CD). In contrast, myeloid cell responses toward innate stimuli remained broadly augmented. WD-induced transcriptomic and epigenomic reprogramming of myeloid progenitor cells led to increased proliferation and enhanced innate immune responses. Quantitative trait locus (QTL) analysis in human monocytes trained with oxidized low-density lipoprotein (oxLDL) and stimulated with lipopolysaccharide (LPS) suggested inflammasome-mediated trained immunity. Consistently, Nlrp3-/-/Ldlr-/- mice lacked WD-induced systemic inflammation, myeloid progenitor proliferation, and reprogramming. Hence, NLRP3 mediates trained immunity following WD and could thereby mediate the potentially deleterious effects of trained immunity in inflammatory diseases.

Eating more fruits and vegetables may indeed be a good idea.

Soy, Genistein, And Prostate Cancer

The soy isoflavone genistein has a variety of antitumor effects both in cell culture (in vitro) and in animal models (in vivo).  In particular, genistein can have beneficial effects against prostate cancer cells, targeting certain cell signaling pathways as well as targeting certain microRNAs that affect gene expression.  These findings can help explain health benefits of soy as well as identify targets for other therapeutic interventions.  Abstract:

OBJECTIVE:

Genistein is a soy isoflavone that has antitumor activity both in vitro and in vivo. It has been shown that genistein inhibits many type of cancers including prostate cancer (PCa) by regulating several cell signaling pathways and microRNAs (miRNAs). Recent studies suggest that the long non-coding RNAs (lncRNAs) are also involved in many cellular processes. At present there are no reports about the relationship between gensitein, miRNAs and lncRNAs. In this study, we focused on miRNAs, lncRNA that are regulated by genistein and investigated their functional role in PCa.

METHOD:

Microarray (SurePrint G3 Human GE 8×60K) was used for expression profiling of genistein treated and control PCa cells (PC3 and DU145). Functional assay (cell proliferation, migration, invasion, apoptosis and cell cycle assays) were performed with the PCa cell lines, PC3 and DU145. Both in vitro and in vivo (nude mouse) models were used for growth assays. Luciferase reporter assays were used for binding of miR-34a to HOTAIR.

RESULTS:

LncRNA profiling showed that HOTAIR was highly regulated by genistein and its expression was higher in castration-resistant PCa cell lines than in normal prostate cells. Knockdown (siRNA) of HOTAIR decreased PCa cell proliferation, migration and invasion and induced apoptosis and cell cycle arrest. miR-34a was also up-regulated by genistein and may directly target HOTAIR in both PC3 and DU145 PCa cells.

CONCLUSIONS:

Our results indicated that genistein inhibited PCa cell growth through down-regulation of oncogenic HOTAIR that is also targeted by tumor suppressor miR-34a. These findings enhance understanding of how genistein regulates lncRNA HOTAIR and miR-34a in PCa.

What's In The Wine?

Resveratrol, which is found in wine as well as in other foodstuffs, has been thought to have a number of positive health benefits.  Here is a study that shows some activity against bone cancer cells.  Certain signaling pathways are involved, including suppression of Wnt signaling. Abstract:

Osteosarcoma is a high-grade bone sarcoma with strong invasive ability. However, treatment with traditional chemotherapeutic drugs is limited by low tolerability and side effects. Resveratrol has been reported previously to have selective antitumor effect on various tumor cells while little is known about its effects and underlying mechanism in osteosarcoma biology. In this study, we found that resveratrol inhibits proliferation and glycolysis, induces apoptosis and reduces the invasiveness of U2-OS cells in vitro. After treatment with resveratrol, the expression of related Wnt/β-catenin signaling pathway target genes, such as β-catenin, c-myc, cyclin D1, MMP-2 and MMP-9, was downregulated and an increased E-cadherin level was observed as well. Additionally, the dual luciferase assay results also indicated that resveratrol suppressed the activity of Wnt/β-catenin signaling pathway. Interestingly, we noticed that the expression of connexin 43 (Cx43) increased with the prolongation of resveratrol treatment time. To further investigate the relationship between Cx43 and the Wnt/β-catenin signaling pathway in osteosarcoma, we used lentiviral-mediated shRNA to knockdown the expression of Cx43. Knockdown of Cx43 activated the Wnt/β-catenin signaling pathway, promoted proliferation and invasion, and inhibited apoptosis of U2-OS cells. Taken together, our results demonstrate that the antitumor activity of resveratrol against U2-OS cells in vitro occurs through up-regulating Cx43 and E-cadherin, and suppressing the Wnt/β-catenin signaling pathway. Moreover, Cx43 expression is negatively related to the activity of the Wnt/β-catenin pathway in U2-OS cells.

More On Cancer Prevention And Lifestyle

Here is recent news on yet another study linking lifestyle to cancer risk.  These are all things you, as a reader of this blog, should be well aware of by now.  The importance of curbing these behaviors to reduce cancer risk is underscored by these additional data.

Researchers with the American Cancer Society looked at data on cancer incidence and deaths, finding that 42 percent of all cancer cases in the United States -– and nearly half of all cancer deaths – are linked to preventable risk factors like cigarette smoking, exposure to secondhand smoke, excess body weight, alcohol intake and dietary choices.

Cigarette smoking, in particular, was connected to far more cancer cases and deaths than any other single risk factor, accounting for 19 percent of all cancer cases and 28.8 percent of deaths. Overweight and obesity came in second, responsible for 7.8 percent of cases and 6.5 percent of deaths, while alcohol intake was the third most important factor, leading to 5.6 percent of cancer cases and 4 percent of deaths.

Although there are some sex-specific differences as to the relative importance of various risk factors, the bottom line is that these things – smoking/overweight/obese, bad diets, certain STDs, alcohol – are bad for everyone.  Be aware and adjust your life accordingly, to the extent you are able.

Apigenin's Anti-Cancer Properties

The dietary factor apigenin has anti-cancer properties, affecting important cell signaling pathways.  Note this factor is found in many fruits and vegetables, once again showing the importance of those foodstuffs. Also note the comment: “Apigenin appears to have the potential to be developed either as a dietary supplement or as an adjuvant chemotherapeutic agent for cancer therapy.”  Abstract:

Apigenin is a common dietary flavonoid that is abundantly present in many fruits, vegetables and Chinese medicinal herbs and serves multiple physiological functions, such as strong anti-inflammatory, antioxidant, antibacterial and antiviral activities and blood pressure reduction. Therefore, apigenin has been used as a traditional medicine for centuries. Recently, apigenin has been widely investigated for its anti-cancer activities and low toxicity. Apigenin was reported to suppress various human cancers in vitro and in vivo by multiple biological effects, such as triggering cell apoptosis and autophagy, inducing cell cycle arrest, suppressing cell migration and invasion, and stimulating an immune response. In this review, we focus on the most recent advances in the anti-cancer effects of apigenin and their underlying mechanisms, and we summarize the signaling pathways modulated by apigenin, including the PI3K/AKT, MAPK/ERK, JAK/STAT, NF-κB and Wnt/β-catenin pathways. We also discuss combinatorial strategies to enhance the anti-cancer effect of apigenin on various cancers and its use as an adjuvant chemotherapeutic agent to overcome cancer drug resistance or to alleviate other adverse effects of chemotherapy. The functions of apigenin against cancer stem cells are also summarized and discussed. These data demonstrate that apigenin is a promising reagent for cancer therapy. Apigenin appears to have the potential to be developed either as a dietary supplement or as an adjuvant chemotherapeutic agent for cancer therapy.

Molecular Pathway Linking Colon Cancer To A High Fat Diet (And Obesity)

By Attributed to Charles Mellin - WgF1LrUvFdNysA at Google Cultural Institute, zoom level maximum, Public Domain, https://commons.wikimedia.org/w/index.php?curid=13334241

A study has shown a molecular pathway linking obesity and a high fat diet to colon cancer.  Excerpts from the article (italics) with some of my own comments inserted:

Scientists in the U.S. have identified a molecular pathway that appears to play a key role in the link between a high-fat diet (HFD) and the development of colorectal cancer. The research, led by the Cleveland Clinic’s Sheerlarani Karunanithi, and Matthew Kalady, suggests that it may one day be possible to develop drugs that reduce tumor growth associated with obesity and a diet that is high in fat. 

Or people can lose weight and eat lower-fat diets.  What's wrong with that approach?

Their research is published today, in Stem Cell Reports, in a paper titled, “RBP4-STRA6 Pathway Drives Cancer Stem Cell Maintenance and Mediates High-Fat Diet-Induced Colon Carcinogenesis.”

The Cleveland Clinic team’s review of published research indicated that high expression levels of two vitamin A signalling proteins—serum retinol binding protein (RPB4), stimulated by retinoic acid 6 (STRA6)—in colorectal cancer tumors is associated with poor prognosis, increased tumor metastasis and recurrence, and resistance to cancer therapy. The RBP4-STRA6 pathway triggers the JAK2-STAT3 signaling cascade…

That is useful information - perhaps the greatest utility is motivation to lose wright and change diets, as there is now more concrete evidence linking unhealthy eating habits and an unhealthy weight to colon cancer.

...Our data clearly indicate that RBP4-STRA6 pathway is necessary for the optimal expression of stem cell markers such as NANOG, SOX2, and LGR5, and thereby for maintaining the colon CSC pool,” the authors conclude in their published paper. "We have known the influence of diet on colorectal cancer,” commented Matthew Kalady, M.D., colorectal surgeon, and co-director of the Cleveland Clinic Comprehensive Colorectal Cancer Program. “However, these new findings are the first to show the connection between high-fat intake and colon cancer via a specific molecular pathway. We can now build upon this knowledge to develop new treatments aimed at blocking this pathway and reducing the negative impact of a high-fat diet on colon cancer risk."

One could reasonably reduce the risk of a high-fat diet by no longer eating the high-fat diet.

“The interesting finding here is that the high fat diet-induced effects appear to also involve the stem cell program, which is interesting for tumor growth and has implications on therapies, as tumor stem cells are also therapeutically resistant...” 

It would seem therefore if high-fat diets maintain colon cancer stem cells - cells that can "fuel" the tumor and which may be more resistant to therapy - then one can ask: should colon cancer patients be given nutritional programs that take this into account?

There's nothing wrong with developing new therapies, but those therapies should be in addition to healthy eating, not a substitute for it.

Fat, Leptin, Mice, And Colon Cancer

By The original uploader was Bigplankton at English Wikipedia Later versions were uploaded by Sunholm at en.wikipedia. - Human Genome wall for SC99 on ornl.gov. Copied from en.wikipedia; description page is/was here., Public Domain, https://commons.wikimedia.org/w/index.php?curid=1777620 

This study used mice that model colon cancer induced by azoxymethane and dextran sulfate sodium. 

The mice were fed a regular diet or a high-fat diet (HFD), and the researchers found that the HFD-fed mice had more colon inflammation, more tumors, and different gene expression compared to regular-diet mice.  

Some of the changes in the HFD mouse colon were similar to these found in human colon cancer, particularly colon cancer with inflammatory microsatellite instability.  

Leptin and Wnt signaling were altered in the HFD mice, and such alterations are also associated with colon cancer. Upregulation of the leptin pathway is associated with worse overall survival; whereas, Wnt signaling deregulation is often the initiating step in the development of colon cancer.

Taking into account the similarities to the human colon cancer, the importance of diet becomes clear.

Vegetable Extracts And Colon Cancer Cell Growth

Broccoli. By Fir0002 - Own work, GFDL 1.2, https://commons.wikimedia.org/w/index.php?curid=5772317

Here is an interesting paper about colorectal cancer (CRC) that examines the effects of extracts enriched in isothiocyanates (ITCs), which are known to have anti-CRC properties, on different cell culture models of CRC, including more advanced 3-D spheroid approaches. Spheroids are more analogous to actual tumors and represent a useful methodology for analyzing the effects of different agents.  

Abstract:

Colorectal cancer (CRC) recurrence is often attributable to circulating tumor cells and/or cancer stem cells (CSCs) that resist to conventional therapies and foster tumor progression. Isothiocyanates (ITCs) derived from Brassicaceae vegetables have demonstrated anticancer effects in CRC, however little is known about their effect in CSCs and tumor initiation properties. Here we examined the effect of ITCs-enriched Brassicaceae extracts derived from watercress and broccoli in cell proliferation, CSC phenotype and metastasis using a previously developed three-dimensional HT29 cell model with CSC-like traits. Both extracts were phytochemically characterized and their antiproliferative effect in HT29 monolayers was explored. Next, we performed cell proliferation assays and flow cytometry analysis in HT29 spheroids treated with watercress and broccoli extracts and respective main ITCs, phenethyl isothiocyanate (PEITC) and sulforaphane (SFN). Soft agar assays and relative quantitative expression analysis of stemness markers and Wnt/β-catenin signaling players were performed to evaluate the effect of these phytochemicals in stemness and metastasis. Our results showed that both Brassicaceae extracts and ITCs exert antiproliferative effects in HT29 spheroids, arresting cell cycle at G₂/M, possibly due to ITC-induced DNA damage. Colony formation and expression of LGR5 and CD133 cancer stemness markers were significantly reduced. Only watercress extract and PEITC decreased ALDH1 activity in a dose-dependent manner, as well as β-catenin expression. Our research provides new insights on CRC therapy using ITC-enriched Brassicaceae extracts, specially watercress extract, to target CSCs and circulating tumor cells by impairing cell proliferation, ALDH1-mediated chemo-resistance, anoikis evasion, self-renewal and metastatic potential.

Therefore, these vegetable extracts inhibited the growth of the CRC 3-D spheroid cultures, possibly due to damage to cell DNA induced by the ITC component of the extracts.  Other indicators of CRC cell growth and cancer-causing potential were also suppressed, particularly by the watercress extract.  These findings suggest the potential of such extracts for CRC therapeutics.

More about watercress, including possible health concerns about consumption (which need to be noted and considered) is at the link.   For me, I’ll continue eating my broccoli.

More On Diet, Gut Microbiota, And Colorectal Cancer

At left, colorectal cancer diagram, By Blausen Medical Communications, Inc. - Donated via OTRS, see ticket for details, CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=27639260

Certain bacterial species in the gut microbiota enhanced risk of colorectal cancer (CRC).  Can diet influence the risk of developing CRC associated with those bacteria?  The answer seems to be yes, as described in this paper.  Excerpts from the abstract:

Importance: Fusobacterium nucleatum appears to play a role in colorectal carcinogenesis through suppression of the hosts' immune response to tumor. Evidence also suggests that diet influences intestinal F nucleatum. However, the role of F nucleatum in mediating the relationship between diet and the risk of colorectal cancer is unknown.

Objective: To test the hypothesis that the associations of prudent diets (rich in whole grains and dietary fiber) and Western diets (rich in red and processed meat, refined grains, and desserts) with colorectal cancer risk may differ according to the presence of F nucleatum in tumor tissue.

Conclusions and Relevance: Prudent diets rich in whole grains and dietary fiber are associated with a lower risk for F nucleatum - positive colorectal cancer but not F nucleatum - negative cancer, supporting a potential role for intestinal microbiota in mediating the association between diet and colorectal neoplasms.

In summary, diets high in whole grains and fiber reduce risk of CRC associated with F nucleatum, but not for CRC not associated with that species. This is evidence that the gut microbiota plays an important role in mediating the effects of diet on CRC, and further suggests the power of diet and gut microbiota management for cancer prevention.  I’ll be eating my whole grains and fiber.

Folate Restriction And Breast Cancer

An interesting study using cell culture suggests that folate restriction may be beneficial for breast cancer.  Abstract:

Folate coenzymes are involved in biochemical reactions of one-carbon transfer, and deficiency of this vitamin impairs cellular proliferation, migration, and survival in many cell types. Here, the effect of folate restriction on mammary cancer was evaluated using three distinct breast cancer subtypes differing in their aggressiveness and metastatic potential: noninvasive basal-like (E-Wnt), invasive but minimally metastatic claudin-low (M-Wnt), and highly metastatic claudin-low (metM-Wntliver) cell lines, each derived from the same pool of MMTV-Wnt-1 transgenic mouse mammary tumors. NMR-based metabolomics was used to quantitate 41 major metabolites in cells grown in folate-free medium versus standard medium. Each cell line demonstrated metabolic reprogramming when grown in folate-free medium. In E-Wnt, M-Wnt, and metM-Wntliver cells, 12, 29, and 25 metabolites, respectively, were significantly different (P < 0.05 and at least 1.5-fold change). The levels of eight metabolites (aspartate, ATP, creatine, creatine phosphate, formate, serine, taurine and β-alanine) were changed in each folate-restricted cell line. Increased glucose, decreased lactate, and inhibition of glycolysis, cellular proliferation, migration, and invasion occurred in M-Wnt and metM-Wntliver cells (but not E-Wnt cells) grown in folate-free versus standard medium. These effects were accompanied by altered levels of several folate-metabolizing enzymes, indicating that the observed metabolic reprogramming may result from both decreased folate availability and altered folate metabolism. These findings reveal that folate restriction results in metabolic and bioenergetic changes and a less aggressive cancer cell phenotype.

IMPLICATIONS:

Metabolic reprogramming driven by folate restriction represents a therapeutic target for reducing the burden of breast cancer. Mol Cancer Res; 15(2); 1-12. ©2016 AACR.

Of course, one study using "transgenic mouse mammary tumor" cells in a tissue culture model system is not definitive for human patient treatment, and so much more work is needed to better evaluate the role of folate restriction as one therapeutic approach for breast (and other?) cancer. Nevertheless, this is a potentially useful example of the interplay between diet, nutrients, and cancer development.

Everything in moderation, but ban sugar

This is how I summarize the advice from this new article:

"Official advice on low-fat diet and cholesterol is wrong, says health charity".