Anti-CSC effects in human esophageal squamous cell carcinomas and Eca109/9706 cells induced by nanoliposomal quercetin alone or combined with CD 133 antiserum.
CD133 was recently reported to be a cancer stem cell and prognostic marker. Quercetin is considered as a potential chemopreventive agent due to its involvement in suppression of oxidative stress, proliferation and metastasis. In this study, the expression of CD133/CD44 in esophageal carcinomas and Eca109/9706 cells was explored. In immunoflurorescence the locations of CD133+ and multidrug resistance 1 (MDR 1)+ in the same E-cancer cells were coincident, mainly in cytomembranes. In esophageal squamous cell carcinomas detected by double/single immunocytochemistry, small CD133+ cells were located in the basal layer of stratified squamous epithelium, 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-regulation of NF-κBp65, histone deacetylase 1 (HDAC1) and cyclin D1 and up-regulation of caspase-3 were shown by immunoblotting, and attenuated HDAC1 with nuclear translocation and promoted E-cadherin expression were demonstrated by immunocytochemistry. In particular, enhanced E-cadherin expression reflected the reversed epithelial mesenchymal transition (EMT) capacity of nLQ, acting as cancer attenuator/preventive agent. nLQ acting as an HDAC inhibitor induced apoptotic cells detected by TUNEL assay mediated via HDAC-NF-κB signaling. Apoptotic effects of liposomal quercetin (LQ, with cytomembrane-philia) combined with CD133 antiserum were also detected by CD133 immunocytochemistry combined with TUNEL assay. The combination could induce greater apoptotic effects than nLQ induced alone, suggesting a novel anti-CSC treatment strategy.
Molecular Cell Biology Research Center, Medical College of Zhengzhou University, Zhengzhou, China E-mail : zhengng@zzu.edu.cn.
Nai-Gang
NG
Zheng
Sai-Jun
SJ
Mo
Jin-Ping
JP
Li
Jing-Lan
JL
Wu
D000071916:AC133 Antigen; D015703:Antigens, CD / Q000276:immunology*; D000975:Antioxidants / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology*; D015820:Cadherins / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000187:drug effects / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects; D004337:Drug Carriers / Q000008:administration & dosage; D004938:Esophageal Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D000077277:Esophageal Squamous Cell Carcinoma; D006023:Glycoproteins / Q000276:immunology*; D056284:Histone Deacetylase 1 / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007106:Immune Sera / Q000008:administration & dosage*; D008081:Liposomes / Q000008:administration & dosage; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D053758:Nanoparticles / Q000008:administration & dosage; D014411:Neoplastic Stem Cells / Q000378:metabolism; D010455:Peptides / Q000276:immunology*; D011794:Quercetin / Q000008:administration & dosage*; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured
D000071916:AC133 Antigen; D015703:Antigens, CD; D000975:Antioxidants; D015820:Cadherins; D004337:Drug Carriers; D006023:Glycoproteins; D007106:Immune Sera; D008081:Liposomes; D016328:NF-kappa B; C000606023:PROM1 protein, human; D010455:Peptides; D019938:Cyclin D1; D011794:Quercetin; D053148:Caspase 3; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1