Anti-CSC Effects in Human Esophageal Squamous Cell Carcinomas and Eca109/9706 Cells Induced by Nanoliposomal Quercetin Alone or Combined with CD 133 Antiserum

Abstract

CD133 was recently reported to be a cancer stem cell and prognostic marker. Quercetin is considered asa potential chemopreventive agent due to its involvement in suppression of oxidative stress, proliferation andmetastasis. In this study, the expression of CD133/CD44 in esophageal carcinomas and Eca109/9706 cells wasexplored. In immunoflurorescence the locations of CD133+ and multidrug resistance 1 (MDR 1)+ in the sameE-cancer cells were coincident, mainly in cytomembranes. In esophageal squamous cell carcinomas detected bydouble/single immunocytochemistry, small CD133+ cells were located in the basal layer of stratified squamousepithelium, determined as CSLC (cancer stem like cells); CD44+ surrounding the cells appeared in diffuse pattern,and the larger CD44+ (hi) cells were mainly located in the prickle cell layer of the epithelium, as progenitor cells.In E-cancer cells exposed to nanoliposomal quercetin (nLQ with cytomembrane permeability), down-regulationof NF-κBp65, histone deacetylase 1 (HDAC1) and cyclin D1 and up-regulation of caspase-3 were shown byimmunoblotting, and attenuated HDAC1 with nuclear translocation and promoted E-cadherin expression weredemonstrated by immunocytochemistry. In particular, enhanced E-cadherin expression reflected the reversedepithelial mesenchymal transition (EMT) capacity of nLQ, acting as cancer attenuator/preventive agent. nLQacting as an HDAC inhibitor induced apoptotic cells detected by TUNEL assay mediated via HDAC-NF-κBsignaling. Apoptotic effects of liposomal quercetin (LQ, with cytomembrane-philia) combined with CD133antiserum were also detected by CD133 immunocytochemistry combined with TUNEL assay. The combinationcould induce greater apoptotic effects than nLQ induced alone, suggesting a novel anti-CSC treatment strategy.