Vitamin D3 and beta-carotene deficiency is associated with risk of esophageal squamous cell carcinoma - results of a case-control study in China.

OBJECTIVE: The aim was to evaluate roles of vitamin D3 (VD3) and beta-carotene (BC) in the development of esophageal squamous cell carcinoma (ESCC) in a high-risk area, Huai'an District, Huai'an City, China. METHODS: 100 new ESCC diagnosed cases from 2007 to 2008 and 200 residency- age-, and sex-matched healthy controls were recruited. Data were collected from questionnaires, including a food frequency questionnaire (FFQ) to calculate the BC intake, and reversed phase high-performance liquid chromatography (RP-HPLC) was used to measure the serum concentrations of BC and VD3. Odds ratios (OR) and 95% confidence intervals (CI) were calculated in conditional logistic regression models. RESULTS: The average dietary intake of BC was 3322.9 µg (2032.4- 5734.3) in the case group and 3626.8 µg (1961.9-5827.9) in control group per capita per day with no significant difference by Wilcoxon test (p>0.05). However, the levels of VD3 and BC in the case group were significantly lower than in the control group (p<0.05). The OR values of the highest quartile and the lowest quartile of VD3 and BC in serum samples were both 0.13. CONCLUSION: Our results add to the evidence that high circulating levels of VD3 and BC are associated with a reduced risk of ESCC in this Chinese population.

Stimulation of the proliferation of human normal esophageal epithelial cells by fumonisin B1 and its mechanism.

Previous epidemiological studies have demonstrated a correlation between fumonisin B1 (FB1) and human esophageal cancer in China, Iran and South Africa. The purpose of this study was to investigate the effects of FB1 on the proliferation, cell-cycle and apoptosis of normal human esophageal epithelial cells (HEECs) and to explore the molecular mechanisms of these effects. The proliferation of HEECs treated with FB1 was assessed using a colorimetric assay, while analyses of the cell cycle and apoptosis were performed using flow cytometry and the measurement of the protein expressions of genes associated with the cell cycle was conducted using western blotting. The results showed that FB1 stimulated the proliferation of HEECs, decreased the percentage of cells in the G0/G1 phase and reduced apoptosis. The western blotting results showed that FB1 significantly increased the protein expression of cyclin D1 and significantly decreased the protein expression of cyclin E, p21 and p27. The results indicated that FB1 stimulated the proliferation of HEECs by affecting the cell cycle and apoptosis. This mechanism was associated with changes in cyclin D1, cyclin E, p21 and p27 expression.

Serum folate, MTHFR C677T polymorphism and esophageal squamous cell carcinoma risk.

This study examined associations between MTHFR C677T polymorphism and serum folate concentrations with the risk of esophageal precancerous lesions (EPL) and esophageal squamous cell carcinoma (ESCC). The highest quartile of serum folate concentration significantly decreased the risk of ESCC compared with the lowest quartile (OR=0.11; 95% Cl, 0.04-0.33; P<0.05). MTHFR 677 C>T polymorphism was associated with the risk of ESCC by using chi-square tests (P<0.05). For the CT genotype, the risk of ESCC significantly increased in study participants with low serm folate concentrations (≤26.92 µg/L) compared with participants with high serum folate concentrations (>26.92 µg/L) by using multinomial logistic regression models. The MTHFR genotype may further modify associations between serum folate concentrations and the risk of ESCC, but it was not significantly associated with the risk of EPL.

Inhibition of proliferation and induction of apoptosis by the combination of ß-carotene and 1,25-dihydroxyvitamin D3 in human esophageal cancer EC9706 cells.

Esophageal cancer is a common malignant tumor occurring in human esophageal epithelial tissue. The primary purpose of this paper was to define the effects of ß-carotene and 1,25-dihydroxyvitamin D3, alone and in combination, on cell proliferation, cell cycle and apoptosis of human esophageal cancer EC9706 cells. Treatment with different concentrations of ß-carotene and/or 1,25-dihydroxyvitamin D3. MTT assay showed that ß-carotene and 1,25-dihydroxyvitamin D3 significantly inhibited proliferation of EC9706 cells in a dose- and time-dependent manner. Further studies also demonstrated that ß-carotene alone or 1,25-dihydroxyvitamin D3 alone caused a marked increase on the induction of apoptosis in EC9706 cells. The percentage of G0/G1-phase cells significantly increased on addition of 1,25-dihydroxyvitamin D3 alone, but there were no significant changes with ß-carotene alone. These two agents in combination synergistically inhibited cell growth and induced apoptosis. Therefore, our results indicate that ß-carotene and 1,25-dihydroxyvitamin D3 in combination may provide a novel strategy for preventing and treating esophageal cancer.

Luteolin induced-growth inhibition and apoptosis of human esophageal squamous carcinoma cell line Eca109 cells in vitro.

Luteolin is a plant flavonoid which exhibits anti-oxidative, anti-inflammatory and anti-tumor effects. However, the antiproliferative potential of luteolin is not fully understood. In this study, we investigated the effect of luteolin on cell cycling and apoptosis in human esophageal squamous carcinoma cell line Eca109 cells. MTT assays showed that luteolin had obvious cytotoxicity on Eca109 with an IC50 of 70.7±1.72 µM at 24 h. Luteolin arrested cell cycle progression in the G0/G1 phase and prevented entry into S phase in a dose- and time-dependent manner. as assessed by FCM. Luteolin induced apoptosis of Eca109 cells was demonstrated by AO/EB staining assay and annexin V-FITC/PI staining. Moreover, luteolin downregulated the expression of cyclin D1, survivin and c-myc, and it also upregulated the expression of p53, in line with the fact that luteolin was able to inhibit Eca109 cell proliferation.