3-Bromopyruvate inhibits cell proliferation and induces apoptosis in CD133+ population in human glioma.

The study was aimed to investigate the role of 3-bromopyruvate in inhibition of CD133+ U87 human glioma cell population growth. The results demonstrated that 3-bromopyruvate inhibited the viability of both CD133+ and parental cells derived from U87 human glioma cell line. However, the 3-bromopyruvate-induced inhibition in viability was more prominent in CD133+ cells at 10 µM concentration after 48 h. Treatment of CD133+ cells with 3-bromopyruvate caused reduction in cell population and cell size, membrane bubbling, and degradation of cell membranes. Hoechst 33258 staining showed condensation of chromatin material and fragmentation of DNA in treated CD133+ cells after 48 h. 3-Bromopyruvate inhibited the migration rate of CD133+ cells significantly compared to the parental cells. Flow cytometry revealed that exposure of CD133+ cells to 3-bromopyruvate increased the cell population in S phase from 24.5 to 37.9 % with increase in time from 12 to 48 h. In addition, 3-bromopyruvate significantly enhanced the expression of Bax and cleaved caspase 3 in CD133+ cells compared to the parental cells. Therefore, 3-bromopyruvate is a potent chemotherapeutic agent for the treatment of glioma by targeting stem cells selectively.

Overexpression of hERG1 in resected esophageal squamous cell carcinomas: a marker for poor prognosis.

BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the expression and prognostic roles of human ether à go-go related gene (hERG1) potassium channels in resected esophageal squamous cell carcinoma. METHODS: Expression of hERG1 protein and mRNA was detected by immunohistochemistry and reverse transcription PCR in resected esophageal squamous cell carcinomas (ESCCs) and non-cancerous matched tissues, and the correlation was examined between expression of hERG1 protein and clinicopathological factors and prognosis of ESCC patients. RESULTS: Frequency of positive expression of hERG1 protein was 77.9% (53/68), mRNA was 81.8% (9/11). hERG1 protein and mRNA were negatively expressed in all non-cancerous matched tissues. There was no significant correlation between hERG1 protein expression and lymph node metastases, depth of penetration, stage, and other clinicopathological factors. Completeness was 92.5% for hERG1-positive group and 92.0% for hERG1-negative group. ESCC patients with positive expression of hERG1 protein had a significantly shorter postoperative survival time than those with negative expression (median, 30 vs. 56 months). Survival rates at each time-point for hERG1-positive group were lower than that for hERG1-negative group, and hERG1 was identified as an independent prognostic factor of long-term survival by multivariate analysis. CONCLUSION: In ESCC, hERG1 was aberrantly expressed and correlated with poor prognosis after surgery.