curcumin and Barrett-Esophagus

Barrett's esophagus, a metaplasia resulting from a long-standing reflux disease, and its progression to esophageal adenocarcinoma (EAC) are characterized by activation of pro-inflammatory pathways, induced by cytokines.. An in vitro cell culture system representing the sequence of squamous epithelium (EPC1 and EPC2), Barrett's metaplasia (CP-A), dysplasia (CP-B) to EAC (OE33 and OE19) was used to investigate TNF-α-mediated induction of interleukin-8 (IL-8).. IL-6 and IL-8 expressions are increasing with the progression of Barrett's esophagus, with the highest expression of both cytokines in the dysplastic cell line CP-B. IL-8 expression in EAC cells was approx. 4.4-fold (OE33) and eightfold (OE19) higher in EAC cells than in squamous epithelium cells (EPC1 and EPC2). The pro-inflammatory cytokine TNF-α increased IL-8 expression in a time-, concentration-, and stage-specific manner. Furthermore, TNF-α changed the EMT marker profile in OE33 cells by decreasing the epithelial marker E-cadherin and increasing the mesenchymal marker vimentin. The anti-inflammatory compound curcumin was able to repress proliferation and to activate apoptosis in both EAC cell lines.. The increased basal expression levels of IL-8 with the progression of Barrett's esophagus constrain NFκB activation and its contribution in the manifestation of Barrett's esophagus. An anti-inflammatory compound, such as curcumin, could create an anti-inflammatory microenvironment and thus potentially support an increase chemosensitivity in EAC cells.

Topics: Adenocarcinoma; Anti-Inflammatory Agents, Non-Steroidal; Barrett Esophagus; Cell Line; Curcumin; Disease Progression; Drug Evaluation, Preclinical; Epithelial-Mesenchymal Transition; Esophageal Neoplasms; Humans; Interleukin-6; Interleukin-8; Tumor Necrosis Factor-alpha; Vimentin

Provide an enhanced local drug delivery, nanoparticle(s) to minimize systemic effects and achieve enhanced permeability and drug retention into abnormal cells and stroma.. Here a simultaneous loading of lipophilic gold nanorods (GNRs) and curcumin into polymeric nanomicelles made of biocompatible PLGA-b-PEG copolymer through a double re-emulsification process has been developed.. Initial results in vitro on Barrett's esophagus and esophageal adenocarcinoma cell lines demonstrated a significant reduction in cell viability with curcumin and GNRs exposure (p < 0.05). In vivo Barrett's-associated animal model confirmed these results with successful in vivo demonstrated eradication of all high-grade dysplastic premalignant cancer cells.. The synthesis of this novel nanosystem containing GNRs and curcumin is safe and effective in treating and eradicating premalignant esophageal adenocarcinoma.

Topics: Animals; Barrett Esophagus; Cell Line, Tumor; Cell Survival; Curcumin; Drug Delivery Systems; Esophagus; Gold; Humans; Micelles; Nanotubes; Phototherapy; Polyethylene Glycols; Polyglactin 910; Rats

The aim of this study was to investigate the relationship between reflux induced bile insult and MnSOD expression, as well as to examine therapies to preserve MnSOD expression. Additionally, we sought to examine the relationship between MnSOD protein expression and MnSOD enzymatic activity.. MnSOD protein expression was determined by Western blot assay and enzymatic activity was determined by SOD assay. The enzymatic activity of the Het-1A and Bar-T cells were compared both before and after treatments.. MnSOD expression in Het-1A cells was decreased after bile salt exposure. The cells that received MnTBAP or curcumin oil pretreatment showed increased MnSOD expression compared with control untreated cells. The Bar-T cells showed an increase in MnSOD expression after treatment with bile salts. The cells that were pretreated with MnTBAP displayed a larger increase in MnSOD expression compared with the cells that were not pretreated prior to bile salt exposure. The MnSOD activity was significantly different between the untreated cell lines (P = 0.01) and after treatment with bile salt (P = 0.03). Additionally, Bar-T cells had significantly less MnSOD activity than Het-1A cells after each of the pretreatments.. We demonstrated preservation of MnSOD expression in Het-1A cells that were pretreated with antioxidants including MnTBAP, curcumin oil, and certain berry extracts. Additionally, we demonstrated that Bar-T cells have significantly less MnSOD activity than Het-1A cells. These finding have important implications for future studies regarding chemoprevention and the treatment of esophageal cancer.

Topics: Barrett Esophagus; Bile Acids and Salts; Cell Line, Transformed; Curcumin; Disease Progression; Enzyme Activation; Enzyme Inhibitors; Esophageal Neoplasms; Esophagus; Free Radical Scavengers; Fruit; Gastroesophageal Reflux; Humans; Metalloporphyrins; Plant Extracts; Respiratory Mucosa; Superoxide Dismutase

Curcumin has been suggested to possess anti-neoplastic properties. As oesophageal adenocarcinoma (OA) and Barrett's oesophagus (BO) represent a neoplastic series, we postulated that curcumin supplementation may slow neoplastic progression at this site. Our aim was to investigate the effects of curcumin in vitro and in vivo on markers of oesophageal cancer progression.. We investigated the in vitro ability of curcumin to prevent bile acid-induced DNA damage using micronucleus assay and nuclear factor-kappaB (NF-κB) activity in the oesophageal cell lines (OE33) using real-time PCR of the extracted RNA. We also analysed NF-κB p65 activation in curcumin-pre-treated OE33 cells exposed to deoxycholic acid (DCA) using ELISA. In another pilot study, BO patients took a daily 500 mg curcumin tablet for 7 days prior to their endoscopy. In biopsies collected from these patients (n=33, 16 curcumin, 17 control), we examined NF-κB-driven gene expression (interleukin (IL)-8, inhibitor- kappaB (I-κB)) using real-time PCR of the extracted RNA from the biopsy sample. The apoptotic frequency was assessed by counting the number of apoptotic bodies in the epithelial cells from the Barrett's tissue with and without curcumin.. In vitro, curcumin (50 μM) significantly abrogated DNA damage and NF-κB activity induced by bile. Pretreating OE33 cells with curcumin (50 μM) completely abolished the ability of DCA (300 μM) to activate NF-κB. In vivo, IL-8 expression was non-significantly suppressed in the curcumin-supplemented patients compared to the squamous control tissue, whilst also showing a doubling in the apoptotic frequency compared to non-supplemented control patients.. Curcumin abrogated bile-driven effects in vitro. The in vivo data also suggests that curcumin supplementation had beneficial effects (increased apoptosis, potentially reduced NF-κB activity) in the Barrett's tissues themselves, despite poor delivery of the curcumin to the oesophagus.

Topics: Adenocarcinoma; Aged; Anticarcinogenic Agents; Antineoplastic Agents; Apoptosis; Barrett Esophagus; Bile; Biopsy; Cell Line, Tumor; Curcumin; DNA Damage; Enzyme-Linked Immunosorbent Assay; Esophageal Neoplasms; Female; Humans; Male; Middle Aged; NF-kappa B; Pilot Projects; Real-Time Polymerase Chain Reaction

Previous studies have demonstrated a decrease in manganese superoxide dismutase (MnSOD) in both Barrett's epithelium of patients and columnar esophageal epithelium of rats after esophagoduodenal anastomosis (EDA). Curcuma aromatica, an herbal medicine, has been shown to display anti-carcinogenic properties in a wide variety of cell lines and animals. This study was designed to investigate the ability of Curcuma aromatica oil for the prevention of BE and EAC, possibly through its ability to preserve MnSOD function. EDA was performed on rats and Curcuma aromatica oil was administered by i.p. injection. Histological changes and oxidative damage were determined after EDA of 1, 3, and 6 months. MnSOD protein level and MnSOD enzymatic activity were evaluated. Lipid peroxidation was determined by TBARs assay and 8-hydroxy-deoxyguanosine for DNA oxidative damage was measured by immunohistochemical staining. In addition, the indexes of both apoptosis and proliferation were determined by PCNA staining and TUNEL assay, respectively. Severe esophagitis were seen in EDA rats, and morphological transformation within the esophageal epithelium was observed with intestinal metaplasia and EAC identified after 3 months. The EDA rats treated with Curcuma aromatica oil showed that both MnSOD enzymatic activity and protein level were similar to sham controls. Decreased incidences of intestinal metaplasia and EAC also were observed in the EDA rats with Curcuma aromatica oil treatment. Curcuma aromatica oil prevented loss of MnSOD in EDA rat esophageal epithelium, and this preservation of MnSOD is associated with the potential protective mechanism against transformation of esophageal epithelial to BE to EAC.

Topics: Animals; Apoptosis; Barrett Esophagus; Blotting, Western; Catalase; Cell Proliferation; Curcuma; Esophageal Neoplasms; Glutathione; Immunoenzyme Techniques; In Situ Nick-End Labeling; Lipid Peroxidation; Oils, Volatile; Oxidative Stress; Rats; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances