Abstract
Pancreatic cancer is an aggressive malignancy with high metastatic potential. There are several lifestyle-related determinants in its etiology, including diet. Methyl donors are dietary micronutrients which play an important role in fueling vital metabolic pathways, and as bioactive food components provide methyl groups as substrates and cofactors. The imbalanced nutritional status of methyl donors has recently been linked to pathological conditions. Therefore, we hypothesized that dietary methyl donors may improve the physiology of cancer patients, including those with pancreatic cancer, and could be used for intervention therapy. In this study, methyl-donor treatment (L-methionine, choline chloride, folic acid and vitamin B12) of an aggressive pancreatic adenocarcinoma cell line (Panc-1) resulted in significantly increased p21WAF1/Cip1 cyclin-dependent kinase inhibitor levels, along with apoptotic SubG1 fractions. At the same time, phospho-Erk1/2 levels and proliferation rate were significantly reduced. Though methyl-donor treatments also increased the pro-apoptotic protein Bak, Puma and Caspase-9, it failed to elevate cleaved Caspase-3 levels. In addition, the treatment significantly reduced the production of the pro-inflammatory cytokine IL-17a and the transcription factor NFkB. Similarly, a significant decrease in VEGF and SDF-1a levels were detected, which may indicate reduced metastatic potential. As expected, E-cadherin expression was inversely associated with these changes, showing elevated expression after methyl-donor treatment. In summary, we found that methyl donors may have the potential to reduce aggressive and proliferative phenotype of Panc-1 cells. This suggests a promising role of dietary methyl donors for complementing relevant cancer therapies, even in treatment-resistant pancreatic adenocarcinomas.
Highlights
The incidence and mortality rate of pancreatic cancer is growing worldwide, and it is expected that it will be ranked the third leading cause of cancer death by 2025 [1].Pancreatic cancer is an aggressive disease with poor prognosis because of the early presence of metastases, treatment resistance, multiple genetic and epigenetic changes, as well as the fact that it is usually diagnosed at advanced stages [2,3]
Methyl donors Affect Tumor Cell Proliferation is associated with Nuclear factor kappa-B (NFkB)-related inflammation and high metastatic potential [26], as well as MTS proliferation assay was used to detect the effect of methyl-donor treatments on chemoresistance [34], we aimed to examine whether methyl donors could affect: the growth of Panc-1 cancer cell line
We described thatwe methyl donors aremethyl able to donors induce apoptosis attenuate
Summary
Pancreatic cancer is an aggressive disease with poor prognosis because of the early presence of metastases, treatment resistance, multiple genetic and epigenetic changes, as well as the fact that it is usually diagnosed at advanced stages [2,3]. All of these contribute to the only 10% 5-year survival rate. The imbalanced nutritional status of vitamin B2, B6 and B12 can alter the function of folate and methionine cycles and can cause pathological changes [9]. Several studies have discussed the importance of dietary methyl donors in the prevention of and reduction in the risk of cancer development such as breast, colorectal, lung, and pancreatic cancer [10–19]
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