I was just asked by PM about the latest, rather strong confirmation of an elevated risk of cancer in users of folic acid supplements. The person noted that the mechanism is probably because of increased folic acid availability for nucleotide synthesis, for which many cancers have an unusually-high demand, so that the risk would be to people who already have a cancer in their body, whereas "the rest of us" wouldn't be providing 'permission' for growth to nonexistant cancers.

Thiamine deficiency frequently occurs in patients with advanced cancer and therefore thiamine supplementation is used as nutritional support. Thiamine (vitamin B1) is metabolized to thiamine pyrophosphate, the cofactor of transketolase, which is involved in ribose synthesis, necessary for cell replication. Thus, it is important to determine whether the benefits of thiamine supplementation outweigh the risks of tumor proliferation. Using oxythiamine (an irreversible inhibitor of transketolase) and metabolic control analysis (MCA) methods, we measured an in vivo tumour growth control coefficient of 0.9 for the thiamine-transketolase complex in mice with Ehrlich's ascites tumour. Thus, transketolase enzyme and thiamine clearly determine cell proliferation in the Ehrlich's ascites tumour model. This high control coefficient allows us to predict that in advanced tumours, which are commonly thiamine deficient, supplementation of thiamine could significantly increase tumour growth through transketolase activation.

Patients with heart disease in Norway, a country with no fortification of foods with folic acid, had an associated increased risk of cancer and death from any cause if they had received treatment with folic acid and vitamin B12, according to a study in the November 18 issue of JAMA.

Most epidemiological studies have found inverse associations between folate (a B vitamin) intake and risk of colorectal cancer, although such associations have been inconsistent or absent for other cancers, according to background information in the article. "Experimental evidence suggests that folate deficiency may promote initial stages of carcinogenesis, whereas high doses of folic acid may enhance growth of cancer cells. Since 1998, many countries, including the United States, have implemented mandatory folic acid fortification of flour and grain products to reduce the risk of neural-tube birth defects," the authors write. "Recently, concerns have emerged about the safety of folic acid, in particular with respect to cancer risk."

OBJECTIVE: To examine whether antioxidant supplement use is associated with melanoma risk in light of recently published data from the Supplementation in Vitamins and Mineral Antioxidants (SUVIMAX) study, which reported a 4-fold higher melanoma risk in women randomized to receive a supplement with nutritionally appropriate doses of antioxidants. DESIGN: Population-based prospective study (Vitamins and Lifestyle [VITAL] cohort). SETTING: Western Washington State. PARTICIPANTS: A total of 69 671 men and women who self-reported (1) intake of multivitamins and supplemental antioxidants, including selenium and beta carotene, during the past 10 years and (2) melanoma risk factors on a baseline questionnaire. Main Outcome Measure Incident melanoma identified through linkage to the Surveillance, Epidemiology, and End Results (SEER) cancer registry. RESULTS: Cox proportional hazards regression models were used to estimate multivariable relative risks (RRs) and 95% confidence intervals (CIs) for multivitamin, supplemental selenium, and supplemental beta carotene use.

Prostate cancer (CaP) is a significant cause of death in American men. While men residing in Asia show a lower incidence of hormone-refractory prostate cancer (HRPC) compared to Caucasian males, Asian men who move to and live in the United States and adopt a western lifestyle have HRPC rates indistinguishable from Caucasian males. These findings suggest that Asian diets contain ingredients that might protect against the development of HRPC. The identity and mechanisms of such HRPC protective agents remain to be elucidated. An Asian diet may confer protection against HRPC owing to functional synergy between bioactive dietary agents, thus broadening the chemopreventive index, with increased distinct anticancer properties and decreased untoward effects. Here, whether or not a combination of epigallocatechin gallate (EGCG), genistein and quercetin, phytochemicals present in a traditional Asian diet, might exert synergy in controlling proliferation and gene expression was investigated in CWR22Rv1 CaP cells, an in vitro model mimicking CaP transition from AD (androgen dependence) to HRPC.

A research article to be published on September 28, 2009 in the World Journal of Gastroenterology addresses this question. The research team, led by Prof. Zong-fang Li from the Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, investigated the effects of Chrysanthemum indicum extract (CIE) on inhibition of proliferation and on apoptosis, and the underlying mechanisms, in a human HCC MHCC97H cell line.

They examined viable rat hepatocytes and human endothelial ECV304 cells by trypan blue exclusion and MTT assay, respectively, as normal controls. The proliferation of MHCC97H cells was determined by MTT assay. The cellular morphology of MHCC97H cells was observed by phase contrast microscopy. Flow cytometry was performed to analyze cell apoptosis with annexin V/propidium iodide (PI), mitochondrial membrane potential with rhodamine 123 and cell cycle with PI in MHCC97H cells. Apoptotic proteins such as cytochrome C, caspase-9, caspase-3 and cell cycle proteins, including P21 and CDK4, were measured by Western blotting.

ABSTRACT: BACKGROUND: Blueberries may lower relative risk for cancers of the gastrointestinal tract. Previous work indicated an inhibitory effect of consumed blueberry (BB) on formation of aberrant crypt foci (ACF) in colons of male Fisher F344 rats (inbred strain). However, effects of Blueberry on colon tumors and in both genders are unknown.

The cancer stem cell hypothesis suggests that, unlike most cancer cells within a tumor, cancer stem cells resist chemotherapeutic drugs and can regenerate the various cell types in the tumor, thereby causing relapse of the disease. Thus, drugs that selectively target cancer stem cells offer great promise for cancer treatment, particularly in combination with chemotherapy. Here, we show that low doses of metformin, a standard drug for diabetes, inhibits cellular transformation and selectively kills cancer stem cells in four genetically different types of breast cancer. The combination of metformin and a well-defined chemotherapeutic agent, doxorubicin, kills both cancer stem cells and non–stem cancer cells in culture. Furthermore, this combinatorial therapy reduces tumor mass and prevents relapse much more effectively than either drug alone in a xenograft mouse model. Mice seem to remain tumor-free for at least 2 months after combinatorial therapy with metformin and doxorubicin is ended.

"We have found a compound selective for cancer stem cells," said senior author Kevin Struhl, the David Wesley Gaiser professor of biological chemistry and molecular pharmacology at HMS. "What's different is that ours is a first-line diabetes drug."

The findings add to a growing body of preliminary evidence in cells, mice, and people that metformin may improve breast cancer outcomes in people. In this study, the diabetes drug seemed to work independently of its ability to improve insulin sensitivity and lower blood sugar and insulin levels, all of which are also associated with better breast cancer outcomes.

The results fit within the cancer stem cell hypothesis, an intensely studied idea that a small subset of cancer cells has a special power to initiate tumors, fuel tumor growth, and promote recurrence of cancer. Cancer stem cells appear to resist conventional chemotherapies, which kill the bulk of the tumor.

Resveratrol has been found to inhibit the proliferation of a variety of human cancer cell lines, including those from breast, prostate, stomach, colon, pancreatic, and thyroid cancers (2). In animal models, oral administration of resveratrol inhibited the development of esophageal (75), intestinal (76), and mammary (breast) cancer (20, 77) induced by chemical carcinogens. However, oral resveratrol was not effective in inhibiting the development of lung cancer induced by carcinogens in cigarette smoke (78, 79).

Researchers at Huntsman Cancer Institute at the University of Utah have uncovered new information on the notion that sugar "feeds" tumors. The findings may also have implications for other diseases such as diabetes. The research is published in the journal Proceedings of the National Academy of Sciences. "It's been known since 1923 that tumor cells use a lot more glucose than normal cells. Our research helps show how this process takes place, and how it might be stopped to control tumor growth," says Don Ayer, Ph.D., a Huntsman Cancer Institute investigator and professor in the Department of Oncological Sciences at the University of Utah. During both normal and cancerous cell growth, a cellular process takes place that involves both glucose (sugar) and glutamine (an amino acid). Glucose and glutamine are both essential for cell growth, and it was long assumed they operated independently, but Ayer's research shows they are inter-dependent. He discovered that by restricting glutamine availability, glucose utilization is also stopped.

Cells don't like to be alone. In the early stages of tumor formation, a cell might be pushed out of its normal home environment due to excessive growth. But a cell normally responds to this homeless state by dismantling its nucleus, packing up its DNA, and offering itself to be eaten by immune system cells. Simply put, the homeless cell kills itself. This process, known as apoptosis, typically stops potential cancer cells before they have a chance to proliferate. Now, researchers from the lab of Harvard Medical School professor of cell biology Joan Brugge have uncovered another mechanism that kills these precancerous, homeless cells. By studying two different types of human breast epithelial cells, the researchers found that when separated from their natural environment, these cells lose their ability to harvest energy from their surroundings. Eventually, they starve.We originally thought that in order for cells to survive outside their normal environment, they would simply need to suppress apoptosis," says Brugge, senior author on the paper, which will appear August 19 online in Nature.

The expression and signaling of the vitamin D receptor (VDR) and peroxisome proliferator-activated receptor (PPAR) alpha, delta, gamma was investigated in the melanoma cell line MeWo. Using real-time PCR, the mRNA of the nuclear receptors (NR) was detected. The strongest expression was found for the VDR, approximately 3-fold higher compared to the expression of PPARalpha or PPARdelta, and the weakest expression was for PPARgamma. After treatment with corresponding ligands, the expression of the VDR, PPARalpha and PPARdelta was elevated up to 5-fold, while the PPARgamma expression was not significantly affected. Treatment with 1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3, calcitrol) resulted in 40% inhibition of MeWo cell proliferation, that was associated with a 5-fold increase in VDR mRNA. Interestingly, cell proliferation was differentially modulated by treatment with the PPAR ligands. While docosahexaenoic acid (DHA) treatment resulted in a statistically significant increase (approximately 10%), the other PPAR ligands inhibited MeWo cell proliferation. GW501516 (PPARdelta ligand) and WY14643 (PPARalpha ligand) both had an antiproliferative effect of approximately 10%.