Folate and its synthetic form, folic acid (FA), are essential vitamins for the regeneration of S-adenosyl methionine molecules, thereby maintaining adequate cellular methylation. The deregulation of DNA methylation is a contributing factor to carcinogenesis, as alterations in genetic methylation may contribute to stem cell reprogramming and dedifferentiation processes that lead to a cancer stem cell (CSC) phenotype. Here, we investigate the potential effects of FA exposure on DNA methylation and colonosphere formation in cultured human colorectal cancer (CRC) cell lines. We show for the first time that HCT116, LS174T, and SW480 cells grown without adequate FA demonstrate significantly impaired colonosphere forming ability with limited changes in CD133, CD166, and EpCAM surface expression. These differences were accompanied by concomitant changes to DNA methyltransferase (DNMT) enzyme expression and DNA methylation levels, which varied depending on cell line. Taken together, these results demonstrate an interaction between FA metabolism and CSC phenotype in vitro and help elucidate a connection between supplemental FA intake and CRC development.

Dichloroacetate (DCA) is a metabolic reprogramming agent that reverses the Warburg effect, causing cancer cells to couple glycolysis to oxidative phosphorylation. This has been shown to induce apoptosis and reduce the growth of various types of cancer but not normal cells. Colorectal cancer cells HCT116, HCT116 p53(-/-), and HCT116 Bax(-/-), were treated with DCA in vitro. Response to treatment was determined by measuring PDH phosphorylation, apoptosis, proliferation, and cell cycle. Molecular changes associated with these responses were determined using western immunoblotting and quantitative PCR. Treatment with 20 mM DCA did not increase apoptosis, despite decreasing levels of anti-apoptotic protein Mcl-1 after 6 h, in any of the cell lines observed. Mcl-1 expression was stabilized with MG-132, an inhibitor of proteasomal degradation. A decrease in Mcl-1 correlated with a decrease in proliferation, both of which showed dose-dependence in DCA treated cells. Cells showed nuclear localization of Mcl-1, however cell cycle was unaffected by DCA treatment. These data suggest that a reduction in the prosurvival Bcl-2 family member Mcl-1 due to increased proteasomal degradation is correlated with the ability of DCA to reduce proliferation of HCT116 human colorectal cancer cells without causing apoptosis.

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Background Inexperience and forgetting perioperative care instruction are significant drivers of parental stress during pediatric tonsillectomy care. With the widespread use of mobile technology, parents now desire a system that provides them with information that is timely, accessible, and comprehensive. Tonsil-Text-To-Me (TTTM) is a text messaging system that sends out automated and timed texts to parents of children who are undergoing tonsillectomy. Objective The objective of this study was to pilot-test TTTM to assess for feasibility and usability and collect suggestions for system improvements desired by parents from a pediatric otolaryngology text message service. Methods Parents of pediatric patients who were being scheduled for tonsillectomy with or without adenoidectomy were prospectively enrolled. An exploratory qualitative study using a semistructured interview guide was performed after parents received the automated texts 2 weeks before and 1 week after their child’s surgery. Results A total of 7 parents were interviewed (data saturation was reached). Participants were all of maternal relation to the patient. Overall, all parents felt that the TTTM service was an improvement to the current standard model of information delivery. Parents also reported that the text messages reduced their anxiety and improved their performance when caring for their children during the perioperative period. No parents expressed privacy concerns about receiving texts and regarding the information included in the messages. Service suggestions showed that parents were eager for more information and had a high threshold for message reception regarding their child’s surgical care. Conclusions All parents expressed enthusiasm for a text message service during their child’s tonsillectomy perioperative period. The care instructions and reminders provided to parents via automated and timed text messages may be a strategy to improve information delivery in a simple and accessible format that could empower families in their own health care.

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