Barrett's Esophagus and β-carotene Therapy: Symptomatic Improvement in GERD and Enhanced HSP70 Expression in Esophageal Mucosa

Abstract

Introduction: Epidemiological studies suggest a protective role for β-carotene with several malignancies. Esophageal adenocarcinoma frequently arises from Barrett's esophagus (BE). We postulated that β-carotene therapy maybe protective in BE. Materials and Method: We conducted a prospective study in which 25 mg of β-carotene was administered daily for six-months to six patients. Each patient underwent upper endoscopy before and after therapy and multiple mucosal biopsies were obtained. Additionally, patients completed a gastroesophageal reflux disease (GERD) symptoms questionnaire before and after therapy and severity score was calculated. To study the effect of β-carotene at molecular level, tissue extracts of the esophageal mucosal biopsy were subjected to assessment of heat-shock protein 70 (HSP70). Results: A significant (p<0.05) reduction in mean GERD symptoms severity score from 7.0±2.4 to 2.7±1.7 following β-carotene therapy was noted. Measurement of Barrett's segment also revealed a significant reduction in mean length after therapy. In fact, two patients had complete disappearance of intestinal metaplasia. Furthermore, marked enhancement of HSP70 expression was demonstrated in biopsy specimens from Barrett's epithelium in four cases that were tested. Conclusions: Longterm β-carotene therapy realizes amelioration of GERD symptoms along with restitution of the histological and molecular changes in esophageal mucosa of patients with BE, associated with concurrent increase in mucosal HSP70 expression.

Oral Microbiome Composition Reflects Prospective Risk for Esophageal Cancers

“…Higher fruit and vegetable intake and higher beta-carotene intake have been associated with reduced EAC risk (4,45). Additionally, beta-carotene therapy was shown to ameliorate GERD symptoms (46). Bacterial biosynthesis of siderophores (iron-chelating compounds) was associated with higher EAC risk.…”

Cross-talk among metabolic parameters, esophageal microbiota, and host gene expression following chronic exposure to an obesogenic diet

“…Studies have shown that carotenoids have antioxidant, anti-apoptotic, and anti-inflammatory properties27. In the esophagus, long-term β-carotene therapy has been shown to be beneficial in both patients with GERD and BE28. Further, epidemiological studies have found that an increased intake of β-carotene was associated with a decreased risk of BE629.…”

Marked Inhibition of Cellular Proliferation in the Normal Human Esophageal Epithelial Cells and Human Esophageal Squamous Cancer Cells in Culture by Carotenoids: Role for Prevention and Early Treatment of Esophageal Cancer

“…Barret's esophagus. In fact we have previously demonstrated in our study that β-carotene therapy reduced the mean length of Barret's segment and also caused restoration of histological and molecular changes in esophageal mucosa of patients with Barret's esophagus (Dutta et al, 2012). Thus, by targeting the HEE cells, carotenes may serve as an important preventive modality for esophageal cancer.…”

“…3HTdR uptake was performed using a modification of the method described previously (Dutta et al, 2012). On the day of the experiment, HEE/HESC cells were incubated with or without various concentrations of α-carotene, β-carotene, or a combination of α-and β-carotene, respectively, for 20 h at 37 o C in a CO 2 incubator for different periods of time (Days 1,3,5,7,9,11,15).…”