Inhibitory effect of vitamin K1 on growth and polyamine biosynthesis of human gastric and colon carcinoma cell lines.

Gastric and colon cancers remain the leading cause of cancer mortality throughout the world. Since the gastrointestinal tract works in a constant link with the external environment, chemoprevention by dietary constituents could represent a possible approach to reduce cancer risk. Dietary vitamin K1 (VK1) has been shown to prevent the growth of many types of cancer cells. However, no data are available on possible different susceptibility to VK1 by gastric or colon neoplastic cell lines. Moreover, the exact mechanism of action of VK1 is still object of investigation, even if it has been reported that VK1 may induce cell cycle arrest and apoptosis. Therefore, molecules affecting cell growth such as the natural polyamines could be of interest in VK1 action. The aim of the present study was to investigate the effects of increasing concentrations of VK1 (from 10 to 200 µM) administered up to 72 h, on the cell proliferation and apoptosis of a gastric (HGC-27) and a colon (SW480) cancer cell line. Additionally, the polyamine biosynthesis and the MAPK pathway were also examined. VK1 treatments caused an inhibition of cell proliferation and an induction of apoptosis in both cell lines, with a concomitant significant decrease of the polyamine biosynthesis, increased phospho-ERK 1/2 expression was also observed. A different proliferative behavior and a different response to VK1 by gastric and colon cancer cells was evident, with colon cells showing a more pronounced susceptibility to VK1 action. VK1 is safe and without known toxicities in adult humans, consequently it could be effective in prevention and treatment of selected gastrointestinal neoplasms. Protocols based on the use of VK1, along with polyamine inhibitors and/or analogues, could represent a suitable alternative option for improving the efficacy of chemoprevention and treatment in future strategies for gastrointestinal cancer management.

Gut peptide profile and chemotherapy-associated dyspepsia syndrome in patients with breast cancer undergoing FEC60 chemotherapy.

AIM: The association of motilin, ghrelin, leptin, gastrin, pepsinogen (PG) I and II with cancer chemotherapy-associated dyspepsia syndrome (CADS) was investigated in 35 patients with breast cancer receiving first cycle of 5-fluorouracil, cyclophosphamide, epirubicin (FEC60) chemotherapy. PATIENTS AND METHODS: The onset of dyspeptic symptoms on days 3 and 10 after chemotherapy identified patients with and without CADS. Gastrointestinal symptoms were scored with the Gastrointestinal Symptom Scoring Rate (GSRS) questionnaire. Gastrointestinal peptides were evaluated by enzyme-linked immunosorbent assay. RESULTS: Twenty-one patients (60%) had CADS. The area under the curve (AUC) of ghrelin was higher, whereas that of PGI, PGII and motilin were lower in patients with CADS compared to those without. In patients with CADS, the AUC of PGI and PGII negatively correlated with the GSRS indigestion cluster. CONCLUSION: Impairment of gastrointestinal motility suggested by low motilin concentrations and mucosal damage mirrored by an increase of ghrelin seem to be involved in the onset of CADS in patients during chemotherapy for breast cancer.

The effects of fluorouracil, epirubicin, and cyclophosphamide (FEC60) on the intestinal barrier function and gut peptides in breast cancer patients: an observational study.

BACKGROUND: Several GI peptides linked to intestinal barrier function could be involved in the modification of intestinal permeability and the onset of diarrhea during adjuvant chemotherapy. The aim of the study was to evaluate the circulating levels of zonulin, glucagon-like peptide-2 (GLP-2), epidermal growth factor (EGF) and ghrelin and their relationship with intestinal permeability and chemotherapy induced diarrhea (CTD). METHODS: Sixty breast cancer patients undergoing an FEC60 regimen were enrolled, 37 patients completed the study. CTD(+) patients were discriminated by appropriate questionnaire and criteria. During chemotherapy, intestinal permeability was assessed by lactulose/mannitol urinary test on day 0 and day 14. Zonulin, GLP-2, EGF and ghrelin circulating levels were evaluated by ELISA tests at five time-points (days 0, 3, 10, 14, and 21). RESULTS: During FEC60 administration, the lactulose/mannitol ratio was significantly higher on day 14 than at baseline. Zonulin levels were not affected by chemotherapy, whereas GLP-2 and EGF levels decreased significantly. GLP-2 levels on day 14 were significantly lower than those on day 0 and day 3, while EGF values were significantly lower on day 10 than at the baseline. In contrast, the total concentrations of ghrelin increased significantly at day 3 compared to days 0 and 21, respectively. Ten patients (27%) suffered from diarrhea. On day 14 of chemotherapy, a significant increase of the La/Ma ratio occurred in CTD(+) patients compared to CTD(-) patients. With regards to circulating gut peptides, the AUCg of GLP-2 and ghrelin were significantly lower and higher in CTD(+) patients than CTD(-) ones, respectively. Finally in CTD(+) patients a significant and inverse correlation between GLP-2 and La/Ma ratio was found on day 14. CONCLUSIONS: Breast cancer patients undergoing FEC60 showed alterations in the intestinal permeability, which was associated with modifications in the levels of GLP-2, ghrelin and EGF. In CTD(+) patients, a different GI peptide profile and increased intestinal permeability was found in comparison to CTD(-) patients. This evidence deserves further studies for investigating the potentially different intestinal luminal and microbiota conditions. TRIAL REGISTRATION: Clinical trial NCT01382667.