curcumin has been researched along with Esophageal-Neoplasms* in 29 studies
4 review(s) available for curcumin and Esophageal-Neoplasms
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Unprecedented community containment measures were taken following the recent outbreak of COVID-19 in Italy. The aim of the study was to explore the self-reported future compliance of citizens with such measures and its relationship with potentially impactful psychological variables.. An online survey was completed by 931 people (18-76 years) distributed across the Italian territory. In addition to demographics, five dimensions were measured: self-reported compliance with containment measures over time (today, at 7, 14, 30, 60, 90, and 180 days from now) at three hypothetical risk levels (10, 50, 90% of likelihood of contracting the COVID-19), perceived risk, generalized anxiety, intolerance of uncertainty, and relevance of several psychological needs whose satisfaction is currently precluded.. The duration of containment measures plays a crucial role in tackling the spread of the disease as people will be less compliant over time. Psychological needs of citizens impacting on the compliance should be taken into account when planning an easing of the lockdown, along with interventions for protecting vulnerable groups from mental distress.. La apendicitis aguda (AA) es la urgencia quirúrgica abdominal más frecuente. No encontramos estudios específicos que evalúen el impacto de la pandemia causada por el coronavirus 2 (SARS-Cov-2) sobre la AA y su tratamiento quirúrgico. Analizamos la influencia de esta nueva patología sobre la AA.. Estudio observacional retrospectivo en pacientes intervenidos por AA desde enero hasta abril de 2020. Fueron clasificados según el momento de la apendicectomía, antes de la declaración del estado de alarma (Pre-COVID19) y después de la declaración del estado de alarma (Post-COVID19) en España. Se evaluaron variables demográficas, duración de la sintomatología, tipo de apendicitis, tiempo quirúrgico, estancia hospitalaria y complicaciones postoperatorias.. La pandemia por SARS-Cov-2 influye en el momento de diagnóstico de la apendicitis, así como en su grado de evolución y estancia hospitalaria. La peritonitis fue lo más frecuentemente observado. Una sospecha y orientación clínica más temprana, es necesaria para evitar un manejo inadecuado de este trastorno quirúrgico común.. The primary outcome is improvement in PaO. Findings will provide timely information on the safety, efficacy, and optimal dosing of t-PA to treat moderate/severe COVID-19-induced ARDS, which can be rapidly adapted to a phase III trial (NCT04357730; FDA IND 149634).. None.. The gut barrier is crucial in cirrhosis in preventing infection-causing bacteria that normally live in the gut from accessing the liver and other organs via the bloodstream. Herein, we characterised gut inflammation by measuring different markers in stool samples from patients at different stages of cirrhosis and comparing this to healthy people. These markers, when compared with equivalent markers usually measured in blood, were found to be very different in pattern and absolute levels, suggesting that there is significant gut inflammation in cirrhosis related to different immune system pathways to that seen outside of the gut. This provides new insights into gut-specific immune disturbances that predispose to complications of cirrhosis, and emphasises that a better understanding of the gut-liver axis is necessary to develop better targeted therapies.. La surveillance de l’intervalle QT a suscité beaucoup d’intérêt durant la pandémie de la COVID-19 en raison de l’utilisation de médicaments prolongeant l’intervalle QT et les préoccupations quant à la transmission virale par les électrocardiogrammes (ECG) en série. Nous avons posé l’hypothèse que la surveillance en continu de l’intervalle QT par télémétrie était associée à une meilleure détection des épisodes de prolongation de l’intervalle QT.. Nous avons introduit la télémétrie cardiaque en continu (TCC) à l’aide d’un algorithme de surveillance automatisée de l’intervalle QT dans nos unités de COVID-19. Les mesures automatisées quotidiennes de l’intervalle QT corrigé (auto-QTc) en fonction de la fréquence cardiaque maximale ont été enregistrées. Nous avons comparé la proportion des épisodes de prolongation marquée de l’intervalle QTc (QTc long), définie par un intervalle QTc ≥ 500 ms, chez les patients montrant une suspicion de COVID-19 ou ayant la COVID-19 qui avaient été admis avant et après la mise en place de la TCC (groupe témoin. La surveillance en continu de l’intervalle QT est supérieure à la norme de soins dans la détection des épisodes de QTc long et exige peu d’ECG. La réponse clinique aux épisodes de QTc long est sous-optimale.. Exposure to a model wildfire air pollution source modifies cardiovascular responses to HC challenge, suggesting air pollution sensitizes the body to systemic triggers.. Though the majority of HIV-infected adults who were on HAART had shown viral suppression, the rate of suppression was sub-optimal according to the UNAIDS 90-90-90 target to help end the AIDS pandemic by 2020. Nonetheless, the rate of immunological recovery in the study cohort was low. Hence, early initiation of HAART should be strengthened to achieve good virological suppression and immunological recovery.. Dust in Egyptian laying hen houses contains high concentrations of microorganisms and endotoxins, which might impair the health of birds and farmers when inhaled. Furthermore, laying hens in Egypt seem to be a reservoir for ESBL-producing Enterobacteriaceae. Thus, farmers are at risk of exposure to ESBL-producing bacteria, and colonized hens might transmit these bacteria into the food chain.. The lack of significant differences in the absolute changes and relative ratios of injury and repair biomarkers by contrast-associated AKI status suggests that the majority of mild contrast-associated AKI cases may be driven by hemodynamic changes at the kidney.. Most comparisons for different outcomes are based on very few studies, mostly low-powered, with an overall low CoE. Thus, the available evidence is considered insufficient to either support or refute CH effectiveness or to recommend one ICM over another. Therefore, further well-designed, larger RCTs are required.. PROSPERO database Identifier: CRD42016041953.. Untouched root canal at cross-section perimeter, the Hero 642 system showed 41.44% ± 5.62% and Reciproc R40 58.67% ± 12.39% without contact with instruments. Regarding the untouched area, Hero 642 system showed 22.78% ± 6.42% and Reciproc R40 34.35% ± 8.52%. Neither instrument achieved complete cross-sectional root canal debridement. Hero 642 system rotary taper 0.02 instruments achieved significant greater wall contact perimeter and area compared to reciprocate the Reciproc R40 taper 0.06 instrument.. Hero 642 achieved higher wall contact perimeter and area but, regardless of instrument size and taper, vital pulp during. The functional properties of the main mechanisms involved in the control of muscle Ca. This study showed that the anti-inflammatory effect of the iron-responsive product DHA in arthritis can be monitored by an iron-like radioactive tracer (. Attenuated vascular reactivity during pregnancy suggests that the systemic vasodilatory state partially depletes nitric oxide bioavailability. Preliminary data support the potential for MRI to identify vascular dysfunction in vivo that underlies PE. Level of Evidence 2 Technical Efficacy Stage 1 J. MAGN. RESON. IMAGING 2021;53:447-455.. La evaluación de riesgo es importante para predecir los resultados postoperatorios en pacientes con cáncer gastroesofágico. Este estudio de cohortes tuvo como objetivo evaluar los cambios en la composición corporal durante la quimioterapia neoadyuvante e investigar su asociación con complicaciones postoperatorias. MÉTODOS: Los pacientes consecutivos con cáncer gastroesofágico sometidos a quimioterapia neoadyuvante y cirugía con intención curativa entre 2016 y 2019, identificados a partir de una base de datos específica, se incluyeron en el estudio. Se utilizaron las imágenes de tomografía computarizada, antes y después de la quimioterapia neoadyuvante, para evaluar el índice de masa muscular esquelética, la sarcopenia y el índice de grasa visceral y subcutánea.. In this in vitro premature infant lung model, HF oscillation of BCPAP was associated with improved CO. Our results showed that HPC significantly promotes neurogenesis after MCAO and ameliorates neuronal injury.. Inflammatory markers are highly related to signs of systemic hypoperfusion in CS. Moreover, high PCT and IL-6 levels are associated with poor prognosis.. These findings indicate that Tetrapleura tetraptera fruit has a protective potential against stroke through modulation of redox and electrolyte imbalances, and attenuation of neurotransmitter dysregulation and other neurochemical dysfunctions. Tetrapleura tetraptera fruit could be a promising source for the discovery of bioactives for stroke therapy. Topics: 3T3-L1 Cells; A Kinase Anchor Proteins; Acetates; Achilles Tendon; Acute Kidney Injury; Acute Pain; Acyclic Monoterpenes; Adenine Nucleotides; Adhesins, Escherichia coli; Adipocytes; Adipocytes, Brown; Adipogenesis; Administration, Inhalation; Administration, Oral; Adrenal Cortex Hormones; Adsorption; Adult; Aeromonas hydrophila; Africa; Aged; Aged, 80 and over; Agrobacterium tumefaciens; Air; Air Pollutants; Air Pollution; Air Pollution, Indoor; Algorithms; Alkaloids; Alkynes; Allosteric Regulation; Amines; Amino Acid Sequence; Amino Acids; Amino Acids, Branched-Chain; Aminoisobutyric Acids; Aminopyridines; Amyotrophic Lateral Sclerosis; Anaerobic Threshold; Angiography; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animal Distribution; Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Ankle Joint; Anti-Bacterial Agents; Anti-HIV Agents; Anti-Inflammatory Agents; Antibodies, Bacterial; Antifungal Agents; 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Pyridines; Pyrrolidines; Quality of Life; Quantum Dots; Quinoxalines; Quorum Sensing; Radiopharmaceuticals; Rain; Random Allocation; Randomized Controlled Trials as Topic; Rats; Rats, Sprague-Dawley; Rats, Wistar; RAW 264.7 Cells; Reactive Oxygen Species; Receptor, Angiotensin, Type 1; Receptor, PAR-1; Receptors, CXCR4; Receptors, Estrogen; Receptors, Glucocorticoid; Receptors, Interleukin-1; Receptors, Interleukin-17; Receptors, Notch; Recombinant Fusion Proteins; Recombinant Proteins; Reducing Agents; Reflex, Startle; Regional Blood Flow; Regression Analysis; Reperfusion Injury; Reproducibility of Results; Republic of Korea; Respiratory Tract Diseases; Retrospective Studies; Reverse Transcriptase Inhibitors; Rhinitis, Allergic; Risk Assessment; Risk Factors; Rituximab; RNA, Messenger; RNA, Ribosomal, 16S; ROC Curve; Rosmarinic Acid; Running; Ruthenium; Rutin; Sarcolemma; Sarcoma; Sarcopenia; Sarcoplasmic Reticulum; SARS-CoV-2; Scavenger Receptors, Class A; Schools; Seasons; Seeds; Sequence Analysis, DNA; Severity of Illness Index; Sex Factors; Shock, Cardiogenic; Short Chain Dehydrogenase-Reductases; Signal Transduction; Silver; Singlet Oxygen; Sinusitis; Skin; Skin Absorption; Small Molecule Libraries; Smoke; Socioeconomic Factors; Soil; Soil Microbiology; Solid Phase Extraction; Solubility; Solvents; Spain; Spectrometry, Mass, Electrospray Ionization; Spectroscopy, Fourier Transform Infrared; Speech; Speech Perception; Spindle Poles; Spleen; Sporothrix; Staphylococcal Infections; Staphylococcus aureus; Stereoisomerism; Stomach Neoplasms; Stress, Physiological; Stroke Volume; Structure-Activity Relationship; Substrate Specificity; Sulfonamides; Surface Properties; Surface-Active Agents; Surveys and Questionnaires; Survival Rate; T-Lymphocytes, Cytotoxic; Tandem Mass Spectrometry; Temperature; Tenofovir; Terpenes; Tetracycline; Tetrapleura; Textiles; Thermodynamics; Thiobarbituric Acid Reactive Substances; Thrombin; Thyroid Hormones; Thyroid Neoplasms; Tibial Meniscus Injuries; Time Factors; Tissue Distribution; Titanium; Toluidines; Tomography, X-Ray Computed; Tooth; Tramadol; Transcription Factor AP-1; Transcription, Genetic; Transfection; Transgender Persons; Translations; Treatment Outcome; Triglycerides; Ubiquinone; Ubiquitin-Specific Proteases; United Kingdom; United States; Up-Regulation; Vascular Stiffness; Veins; Ventricular Remodeling; Viral Load; Virulence Factors; Virus Replication; Vitis; Voice; Voice Quality; Wastewater; Water; Water Pollutants, Chemical; Water-Electrolyte Balance; Weather; Wildfires; Wnt Signaling Pathway; Wound Healing; X-Ray Diffraction; Xenograft Model Antitumor Assays; Young Adult; Zoogloea | 2022 |
Chemopreventive and therapeutic potential of curcumin in esophageal cancer: Current and future status.
Esophageal cancer is a common malignant tumor with an increasing trend during the past three decades. Currently, esophagectomy, often in combination with neoadjuvant chemo- and radiotherapy, is the cornerstone of curative treatment for esophageal cancer. However, esophagostomy is related to significant risks of perioperative mortality and morbidity, as well as lengthy recovery. Moreover, the adjuvant therapies including chemotherapy and radiotherapy are associated with numerous side effects, limiting compliance and outcome. The dietary agent curcumin has been extensively studied over the past few decades and is known to have many biological activities especially in regard to the prevention and potential treatment of cancer. This review summarizes the chemo-preventive and chemotherapeutic potential of curcumin in esophageal cancer in both preclinical and clinical settings. Topics: Animals; Antineoplastic Agents; Carcinogenesis; Chemotherapy, Adjuvant; Curcumin; Disease Models, Animal; Esophageal Neoplasms; Esophagectomy; Humans; Incidence; Neoadjuvant Therapy; Theranostic Nanomedicine; Treatment Outcome | 2019 |
The Therapeutic and Preventive Efficacy of Curcumin and Its Derivatives in Esophageal Cancer
Esophageal cancer is the eighth most common occurring cancer type worldwide and 6th most common among\ the cancer related deaths of which the most common type is squamous cell carcinoma which comprise about 90%\ of esophageal cancer cases. The standard of care for esophageal cancer is neoadjuvant concurrent chemotherapy and\ radiation (NACRT) followed by surgery however the prognosis remains dismal with 5 year survival a meager 10-15%.\ The treatment modalities for esophageal cancer is associated with both long term and short term toxicities. Curcumin\ has been explored as a therapeutic modality as a chemo adjuvant in different cancers due to its low toxicity profile and\ potent anticancer effect however despite lot of promising preclinical data it has not progressed from bench side to bed\ side. The primary reason that has obstructed its application in clinic has been its low bioavailability which was seen\ in different clinical trials but there has been tremendous progress in developing formulations of curcumin which have\ significantly increased its bioavailability and are being tested in clinical trials. Esophageal cancer is associated with\ inflammation that’s why curcumin being a natural antioxidant offer a potential avenue to reduce toxicity of current\ therapeutic modalities in a chemo adjuvant setting while simultaneously targeting different pro oncogenic pathways.\ The present review tries to cover in depth different aspects of curcumin application in treatment of esophageal cancer\ and progress of this potent anticancer agent in its treatment and prevention. Topics: Antineoplastic Agents; Carcinoma, Squamous Cell; Curcumin; Esophageal Neoplasms; Humans; Prognosis | 2019 |
Experimental evidence for cancer preventive elements in foods.
The last decade has witnessed an incredible advance in our understanding of how fruits and vegetables work to prevent cancer. Epidemiological studies have suggested that a diet rich in fruits and vegetables is associated with reduced risk for a number of common cancers. Food chemists and natural product scientists have identified hundreds of 'phytochemicals' that are being evaluated for the prevention of cancer. Food components can modify carcinogenesis in one of five different ways. They may: (1) modify carcinogen activation by inhibiting Phase 1 enzymes; (2) modify how carcinogens are detoxified through Phase 2 pathways; (3) scavenge DNA reactive agents; (4) suppress the abnormal proliferation of early, preneoplastic lesions; and (5) inhibit certain properties of the cancer cell. Topics: Animals; Calcium; Carcinogens; Carotenoids; Cell Division; Colonic Neoplasms; Curcumin; Cytochrome P-450 CYP2E1 Inhibitors; Diet; DNA Adducts; Ellagic Acid; Esophageal Neoplasms; Fruit; Pancreatic Neoplasms; ras Proteins; Reactive Oxygen Species; Skin Neoplasms; Tea; Terpenes; Vegetables; Vitamin D | 1997 |
1 trial(s) available for curcumin and Esophageal-Neoplasms
25 other study(ies) available for curcumin and Esophageal-Neoplasms
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Curcumin inhibits esophageal squamous cell carcinoma progression through down-regulating the circNRIP1/miR-532-3p/AKT pathway.
Curcumin shows an anti-cancer role in many kinds of tumors. However, the mechanism of its anti-tumor function in esophageal squamous cell carcinoma (ESCC) remains largely unknown. Herein, we explored the therapeutic potential of curcumin for esophageal cancer. Curcumin could time- and dose-dependently inhibit ESCC cells activity. Additionally, ESCC cells exposed to 20 μM of curcumin exhibited significantly decreased proliferative and invasive capacities, as well as enhanced cell apoptosis. ESCC tissues and cells exhibited significantly increased circNRIP1 expression when compared to their counterparts. circNRIP1 knockdown markedly impaired cell proliferation, clone formation, cell migration and invasion but promoted apoptosis. Exposure to 10-20 μM of curcumin inhibited circNRIP1 expression, however, overexpression of circNRIP1 could significantly restored the biological characteristics that were inhibited by curcumin exposure in vivo and in vitro. circNRIP1 promoted the malignancy of ESCC by combining miR-532-3p, and downstream AKT3. Curcumin inhibited AKT phosphorylation by up-regulating miR-532-3p expression, thereby inhibiting the activation of the AKT pathway. In summary, curcumin is a potent inhibitor of ESCC growth, which can be achieved through the regulation of the circNRIP1/miR-532-3p/AKT pathway. This research may provide new mechanisms for curcumin to inhibit the malignant development of ESCC. Topics: Cell Line, Tumor; Cell Movement; Cell Proliferation; Curcumin; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Gene Expression Regulation, Neoplastic; Humans; MicroRNAs; Proto-Oncogene Proteins c-akt | 2023 |
Novel T7-Modified pH-Responsive Targeted Nanosystem for Co-Delivery of Docetaxel and Curcumin in the Treatment of Esophageal Cancer.
Although single-drug chemotherapy is still an effective treatment for esophageal cancer, its long-term application is limited by severe side-effects, poor bioavailability, and drug-resistance. Increasing attention has been paid to nanomedicines because of their good biological safety, targeting capabilities, and high-efficiency loading of multiple drugs. Herein, we have developed a novel T7 peptide-modified pH-responsive targeting nanosystem co-loaded with docetaxel and curcumin for the treatment of esophageal cancer.. Firstly, CM-β-CD-PEI-PEG-T7/DTX/CUR (T7-NP-DC) was synthesized by the double emulsion (W/O/W) method. The targeting capacity of the nanocarrier was then investigated by in vitro and in vivo assays using targeted (T7-NP) and non-targeted nanoparticles (NP). Furthermore, the anti-tumor efficacy of T7-NP-DC was studied using esophageal cancer cells (KYSE150 and KYSE510) and a KYSE150 xenograft tumor model.. T7-NP-DC was synthesized successfully and its diameter was determined to be about 100 nm by transmission electron microscopy and dynamic light scattering. T7-NP-DC with docetaxel and curcumin loading of 10% and 6.1%, respectively, had good colloidal stability and exhibited pH-responsive drug release. Good biosafety was observed, even when the concentration was as high as 800 μg/mL. Significant enhancement of T7-NP uptake was observed 6 hours after intravenous injection compared with NP. In addition, the therapeutic efficacy of T7-NP-DC was better than NP-DC and docetaxel in terms of growth suppression in the KYSE150 esophageal cancer model.. The findings demonstrated that T7-NP-DC is a promising, non-toxic, and controllable nanoparticle that is capable of simultaneous delivery of the chemotherapy drug, docetaxel, and the Chinese Medicine, curcumin, for treatment of esophageal cancer. This novel T7-modified targeting nanosystem releases loaded drugs when exposed to the acidic microenvironment of the tumor and exerts a synergistic anti-tumor effect. The data indicate that the nanomaterials can safely exert synergistic anti-tumor effects and provide an excellent therapeutic platform for combination therapy of esophageal cancer. Topics: Animals; Antineoplastic Agents; Curcumin; Docetaxel; Drug Carriers; Drug Liberation; Esophageal Neoplasms; Humans; Hydrogen-Ion Concentration; Nanomedicine; Nanoparticles; Polyethylene Glycols; Polyethyleneimine; Tumor Microenvironment | 2020 |
β-elemene suppresses the malignant behavior of esophageal cancer cells by regulating the phosphorylation of AKT.
Esophageal cancer is a digestive tract malignancy, ranking sixth among the world's deadliest tumor incidence. However, the pathogenesis of esophageal cancer is complex and the prognosis remains poor. Therefore, in-depth study of the pathogenesis and developing effective treatments are of great value for esophageal cancer. β-elemene is a natural monomeric compound derived from the Chinese herbal Curcuma wenyujin. β-elemene has been reported to have anti-tumor effects and used as an adjunct to clinical therapy for multiple cancers. This study aims to explore the effects of β-elemene on esophageal cancer and its related molecular mechanisms.. TE-1 and KYSE-150 cells were used to evaluate the activity of β-elemene on esophageal cancerin vitro and in vivo. Western blot was performed for protein expression assessment. CCK8 assay and cell cycle analysis were used for proliferation testing. Flow cytometry was performed for apoptosis detection. Wound healing assay was subjected to assess the migration ability. Transwell chamber assay was applied to assess the invasion ability. HE staining, TUNEL staining and immunohistochemical staining were used to evaluate the changes in tumor tissues.. We found that β-elemene treatment suppressed proliferation, as well as induced apoptosis of esophageal cancer cells. In addition, β-elemene inhibited the migration and invasion ability of esophageal cancer cells. Furthermore, β-elemene exerted its effects against esophageal cancer by specifically regulating AKT signaling, thereby controlling the expression of PD-L1.. β-elemene inhibits proliferation and metastasis of esophageal cancer cells by regulating the phosphorylation of AKT. Topics: Animals; Antineoplastic Agents, Phytogenic; Apoptosis; B7-H1 Antigen; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cell Survival; Curcuma; Esophageal Neoplasms; Humans; Mice; Mice, Nude; Neoplasm Invasiveness; Oncogene Protein v-akt; Phosphorylation; Sesquiterpenes; Signal Transduction; Wound Healing; Xenograft Model Antitumor Assays | 2020 |
Use of curcumin solution for probe-based confocal laser endomicroscopy of squamous cell carcinoma of the esophagus.
Topics: Aged; Carcinoma, Squamous Cell; Coloring Agents; Curcumin; Endoscopy; Esophageal Neoplasms; Humans; Male; Microscopy, Confocal | 2019 |
Tetrahydrocurcumin, Curcumin, and 5-Fluorouracil Effects on Human Esophageal Carcinoma Cells.
Esophageal cancer responds poorly to traditional therapies, and novel treatments are needed. The phytochemical curcumin is a potential treatment for Esophageal Squamous Cell Carcinoma (ESCC). A curcumin metabolite, tetrahydrocurcumin (THCUR), has anti-cancer effects and greater bioavailability than curcumin.. Evaluate THCUR as an anti-cancer agent relative to curcumin and a standard cancer drug, 5-fluorouracil (5-FU), along with treatment interactions.. Assay cell proliferation and viability following individual and combined delivery of the compounds to three ESSC cell lines (TE-1, TE-8, and KY-5) that have different percentages of Cancer Stem Cells (CSCs).. Curcumin was significantly more effective than 5-FU in all three cell lines. It also had the greatest effect on KY-5 cells, which have the highest CSC properties, consistent with the ability of curcumin to target CSCs. Effects on ESCC cell proliferation were not detected from 40µM THCUR, a dosage above the IC50 of curcumin and 5-FU. However, THCUR at this dosage in combination with 5-FU significantly suppressed TE-1 cell proliferation, but 5-FU alone did not. As TE-1 has low CSC properties relative to the two other cell lines, it was expected to have the least resistance to chemotherapeutic treatments. Surprisingly, TE-1 was the most resistant to inhibition by 5-FU.. These results and the greater stability and water solubility of THCUR than curcumin support further testing of THCUR in combination with standard treatments, particularly for chemoresistant ESCC. In contrast to concerns that curcuminoids taken by patients through diet or diet supplements might interfere with chemotherapy, suppression of 5-FU efficacy by curcumin was not observed. Topics: Antineoplastic Agents; Cell Proliferation; Curcumin; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Fluorouracil; Humans; Molecular Structure; Structure-Activity Relationship; Tumor Cells, Cultured | 2019 |
Combination treatment with highly bioavailable curcumin and NQO1 inhibitor exhibits potent antitumor effects on esophageal squamous cell carcinoma.
Esophageal squamous cell carcinoma (ESCC) is one of the most intractable cancers, so the development of novel therapeutics has been required to improve patient outcomes. Curcumin, a polyphenol from Curcuma longa, exhibits various health benefits including antitumor effects, but its clinical utility is limited because of low bioavailability. Theracurmin. We examined antitumor effects of THC on ESCC cells by cell viability assay, colony and spheroid formation assay, and xenograft models. To reveal its mechanisms, we investigated the levels of reactive oxygen species (ROS) and performed microarray gene expression analysis. According to those analyses, we focused on NQO1, which involved in the removal of ROS, and examined the effects of NQO1-knockdown or overexpression on THC treatment. Moreover, the therapeutic effect of THC and NQO1 inhibitor on ESCC patient-derived xenografts (PDX) was investigated.. THC caused cytotoxicity in ESCC cells, and suppressed the growth of xenografted tumors more efficiently than curcumin. THC increased ROS levels and activated the NRF2-NMRAL2P-NQO1 expressions. Inhibition of NQO1 in ESCC cells by shRNA or NQO1 inhibitor resulted in an increased sensitivity of cells to THC, whereas overexpression of NQO1 antagonized it. Notably, NQO1 inhibitor significantly enhanced the antitumor effects of THC in ESCC PDX tumors.. These findings suggest the potential usefulness of THC and its combination with NQO1 inhibitor as a therapeutic option for ESCC. Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Cell Line, Tumor; Cell Survival; Curcumin; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Gene Expression Regulation, Neoplastic; Humans; Male; Mice; Mice, Hairless; Mice, Inbred C57BL; Mice, SCID; NAD(P)H Dehydrogenase (Quinone); RNA, Small Interfering; Xenograft Model Antitumor Assays | 2019 |
Preclinical Study of Novel Curcumin Analogue SSC-5 Using Orthotopic Tumor Xenograft Model for Esophageal Squamous Cell Carcinoma.
Tumor xenograft model is an indispensable animal cancer model. In esophageal squamous cell carcinoma (ESCC) research, orthotopic tumor xenograft model establishes tumor xenograft in the animal esophagus, which allows the study of tumorigenesis in its native microenvironment.. In this study,we described two simple and reproducible methods to develop tumor xenograft at the cervical or the abdominal esophagus in nude mice by direct injection of ESCC cells in the esophageal wall.. In comparing these two methods, the cervical one presented with more clinically relevant features, i.e., esophageal stricture, body weight loss and poor survival. In addition, the derived tumor xenografts accompanied a rapid growth rate and a high tendency to invade into the surrounding structures. This model was subsequently used to study the anti-tumor effect of curcumin, which is known for its potential therapeutic effects in various diseases including cancers, and its analogue SSC-5. SSC-5 was selected among the eight newly synthesized curcumin analogues based on its superior anti-tumor effect demonstrated in an MTT cell proliferation assay and its effects on apoptosis induction and cell cycle arrest in cultured ESCC cells. Treatment of orthotopic tumor-bearing mice with SSC-5 resulted in an inhibition in tumor growth and invasion.. Taken together, we have established a clinically relevant orthotopic tumor xenograft model that can serve as a preclinical tool for screening new anti-tumor compounds, e.g., SSC-5, in ESCC. Topics: Abdomen; Animals; Catechols; Cell Line, Tumor; Cell Proliferation; Cell Survival; Cervix Uteri; Curcumin; Drug Screening Assays, Antitumor; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Female; Humans; Mice; Mice, Nude; Neoplasm Transplantation; Xenograft Model Antitumor Assays | 2018 |
The effect of curcumin on cell adhesion of human esophageal cancer cell.
Esophageal cancer is the 8th most common cancers worldwide and the 6th most common cause of death among cancers. Curcumin has been reported to have the function of anti-inflammatory, antioxidant, anti-rheumatoid, and anti-atherosclerosis role. It can also reduce lipid, eliminate free radicals and inhibit the growth of the tumor. Many reports had suggested that curcumin has shown great potential in the treatment of tumors by inducing apoptosis. Little is known about the effects of curcumin on cell adhesion of tumor cancer. Therefore, in this study, we attempted to look for a new approach to target resistant cells and improve efficacy without toxicity.. Human esophageal cancer cell line (Eca-109 cells) was cultured. Cell adhesion was detected under a microplate reader. Reactive oxygen species were measured using Fluostar Omega Spectrofluorimeter. SOD activity and GSH content in cells were detected by commercial determination kit. The expression of p-JAK, p-STAT3 and STAT3 were measured by Western blot and RT-PCR.. Cell adhesion assay showed curcumin enhances cell-cell adhesion and cell-matrix adhesion in Eca-109 cells. ROS levels, SOD activity and total GSH content were detected and the results showed curcumin decreases intracellular ROS levels but increases SOD activity and total GSH content. Then, NAC (ROS inhibitor) and ICI (ER inhibitor) were pre-treated. Results showed ICI reversed the decreasing of intracellular ROS levels and the increasing of SOD activity and total GSH content affected by curcumin, but NAC had no such impact. Taken together, ER rather than ROS involves in cell adhesion affected by curcumin. Meanwhile, the downregulating of p-JAK, p-SATA3 and total STAT3 were caused by curcumin but NAC had no such influence. They were reversed by ICI, but NAC had no such influence.. Curcumin could increase cell adhesion through inhibiting JAK/STAT3 mediated by ER in Eca-109. Topics: Acetylcysteine; Apoptosis; Cell Adhesion; Cell Line, Tumor; Curcumin; Esophageal Neoplasms; Fulvestrant; Glutathione; Humans; Reactive Oxygen Species; Signal Transduction; STAT3 Transcription Factor; Superoxide Dismutase | 2018 |
Response to TNF-α Is Increasing Along with the Progression in Barrett's 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 | 2017 |
Curcumin inhibits Ec109 cell growth via an AMPK-mediated metabolic switch.
Glycolytic enzymes are always greatly increased in cancer cells. Whether metabolic reprogramming is involved in curcumin-mediated inhibition of cancer cell growth is unknown.. In this study, cell viability was assayed with MTS analysis; cell cycle was measured with flow cytometry analysis. RT-PCR and western blotting were used to analyse the mRNA and protein expression, respectively.. Here we demonstrated that curcumin inhibited cancer cell growth, especially for Ec109 cells. Curcumin induced cell cycle arrest at G2/M phase. Curcumin caused a significant down-regulation of glycolytic enzymes expressions in a dose-dependent manner. Our results further indicated that the AMPK was required for curcumin-mediated down-regulation of glycolytic enzymes. AMPK-mediated down-regulation of glycolytic enzymes blocked Ec109 cell growth.. Taken together, our results revealed that the AMPK-mediated metabolic switch plays an important role in esophageal cancer cell growth. Topics: AMP-Activated Protein Kinases; Curcumin; Down-Regulation; Enzyme Inhibitors; Esophageal Neoplasms; G2 Phase Cell Cycle Checkpoints; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Glycolysis; HeLa Cells; Humans; M Phase Cell Cycle Checkpoints | 2015 |
[Curcumin induces apoptosis by PTEN/PI3K/AKT pathway in EC109 cells].
To study the molecular mechanism of curcumin in human esophageal carcinoma cell line (EC109).. EC109 cells were cultivated in vitro. When 80%-90% confluence was reached, they were treated with curcumin in different concentrations (15-120 µmol/L). The effects on cell proliferation were examined by CCK-8 colorimetry. The ultrastructure of EC109 cells were detected with transmission electron microscope(TEM). The cells apoptosis was observed with laser confocal microscope(LCM) by AnnexinV-FITC/PI double staining. The proteins level of PTEN, AKT, GSK3β and Caspase 3 were tested by flow cytometry(FCM) .. CCK-8 test showed that curcumin could inhibit the proliferation of EC109 cells in a time- and concentration-dependent manner. TEM and LCM examinations indicated that curcumin could make EC109 cells apoptosis. The data of FCM showed that curcumin could increase the expression of PTEN, GSK3β and Caspase 3, decreased the expression of AKT.. The effects of curcumin on inhibiting proliferation and promoting apoptosis of EC109 cells were related with increased expression of PTEN and inhibition of PI3K/AKT signaling pathway. Topics: Apoptosis; Caspase 3; Cell Line, Tumor; Cell Proliferation; Curcumin; Esophageal Neoplasms; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Humans; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; PTEN Phosphohydrolase; Signal Transduction | 2015 |
Molecular characterization of antitumor effects of the rhizome extract from Curcuma zedoaria on human esophageal carcinoma cells.
Curcuma zedoaria has been used as a traditional agent against malignant diseases. To elucidate detailed mechanisms producing such an activity, characterization and determination of molecular mechanisms of its antitumor effects was conducted. Inhibiting activities against cell proliferation, invasion and colony formation, and expression levels of corresponding molecules were investigated using human esophageal cancer TE-8 cells treated with the rhizome extract from C. zedoaria. Antitumor effect of the extract administered orally was also examined in tumor-bearing mice. The extract possessed strong anti-proliferation and invasion activities against TE-8 cells. Further, upregulated PTEN and downregulated phosphorylated Akt, mTOR and STAT3 expressions in the cells were induced shortly after treatment with the extract, followed by attenuation of FGFR1 and MMP-2, activation of caspase-9, caspase-3 and PARP, and suppression of Bcl-2 expressions, which led the cells to apoptotic cell death. Furthermore, tumor formation in mice was significantly suppressed through the oral administration of the extract. Taken together, these results suggest that the C. zedoaria extract could be a promising agent against esophageal cancer. Topics: Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Blotting, Western; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Proliferation; Curcuma; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Female; Humans; Mice; Mice, Inbred BALB C; Mice, Nude; Plant Extracts; Rhizome; Xenograft Model Antitumor Assays | 2015 |
Suppressing the formation of lipid raft-associated Rac1/PI3K/Akt signaling complexes by curcumin inhibits SDF-1α-induced invasion of human esophageal carcinoma cells.
Stromal cell-derived factor-1α (SDF-1α) is a ligand for C-X-C chemokine receptor type 4 (CXCR4), which contributes to the metastasis of cancer cells by promoting cell migration. Here, we show that the SDF-1α/CXCR4 axis can significantly increase invasion of esophageal carcinoma (EC) cells. We accomplished this by examining the effects of CXCR4 knockdown as well as treatment with a CXCR4-neutralizing antibody and the CXCR4-specific inhibitor AMD3100. Curcumin suppressed SDF-1α-induced cell invasion and matrix metalloproteinase-2 (MMP-2) promoter activity, cell surface localization of CXCR4 at lipid rafts, and lipid raft-associated ras-related C3 botulinum toxin substrate 1 (Rac1)/phosphatidylinositol 3-kinase (PI3K) p85α/Akt signaling. Curcumin inhibited SDF-1α-induced cell invasion by suppressing the Rac1-PI3K signaling complex at lipid rafts but did not abrogate lipid raft formation. We further demonstrate that the attenuation of lipid raft-associated Rac1 activity by curcumin was critical for the inhibition of SDF-1α-induced PI3K/Akt/NF-κB activation, cell surface localization of CXCR4 at lipid rafts, MMP-2 promoter activity, and cell invasion. Collectively, our results indicate that curcumin inhibits SDF-1α-induced EC cell invasion by suppressing the formation of the lipid raft-associated Rac1-PI3K-Akt signaling complex, the localization of CXCR4 with lipid rafts at the cell surface, and MMP-2 promoter activity, likely through the inhibition of Rac1 activity. Topics: Antineoplastic Agents; Apoptosis; Blotting, Western; Carcinoma, Squamous Cell; Cell Movement; Cell Proliferation; Chemokine CXCL12; Curcumin; Esophageal Neoplasms; Flow Cytometry; Humans; Immunoprecipitation; Male; Matrix Metalloproteinase 2; Membrane Microdomains; Middle Aged; Neoplasm Invasiveness; NF-kappa B; Nuclear Proteins; Phosphatidylinositol 3-Kinases; Phosphorylation; Proto-Oncogene Proteins c-akt; rac1 GTP-Binding Protein; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Signal Transduction; Transcription Factors; Tumor Cells, Cultured | 2014 |
Suppression of esophageal cancer cell growth using curcumin, (-)-epigallocatechin-3-gallate and lovastatin.
To determine the effects of curcumin, (-)-epigallocatechin-3-gallate (EGCG), lovastatin, and their combinations on inhibition of esophageal cancer.. Esophageal cancer TE-8 and SKGT-4 cell lines were subjected to cell viability methyl thiazolyl tetrazolium and tumor cell invasion assays in vitro and tumor formation and growth in nude mouse xenografts with or without curcumin, EGCG and lovastatin treatment. Gene expression was detected using immunohistochemistry and Western blotting in tumor cell lines, tumor xenografts and human esophageal cancer tissues, respectively.. These drugs individually or in combinations significantly reduced the viability and invasion capacity of esophageal cancer cells in vitro. Molecularly, these three agents reduced the expression of phosphorylated extracellular-signal-regulated kinases (Erk1/2), c-Jun and cyclooxygenase-2 (COX-2), but activated caspase 3 in esophageal cancer cells. The nude mouse xenograft assay showed that EGCG and the combinations of curcumin, EGCG and lovastatin suppressed esophageal cancer cell growth and reduced the expression of Ki67, phosphorylated Erk1/2 and COX-2. The expression of phosphorylated Erk1/2 and COX-2 in esophageal cancer tissue specimens was also analyzed using immunohistochemistry. The data demonstrated that 77 of 156 (49.4%) tumors expressed phosphorylated Erk1/2 and that 121 of 156 (77.6%) esophageal cancers expressed COX-2 protein. In particular, phosphorylated Erk1/2 was expressed in 23 of 50 (46%) cases of esophageal squamous cell carcinoma (SCC) and in 54 of 106 (50.9%) cases of adenocarcinoma, while COX-2 was expressed in 39 of 50 (78%) esophageal SCC and in 82 of 106 (77.4%) esophageal adenocarcinoma.. The combinations of curcumin, EGCG and lovastatin were able to suppress esophageal cancer cell growth in vitro and in nude mouse xenografts, these drugs also inhibited phosphorylated Erk1/2, c-Jun and COX-2 expression. Topics: Animals; Anticarcinogenic Agents; Anticholesteremic Agents; Catechin; Cell Line, Tumor; Curcumin; Cyclooxygenase 2; Cyclooxygenase Inhibitors; Esophageal Neoplasms; Extracellular Signal-Regulated MAP Kinases; Gene Expression; Humans; JNK Mitogen-Activated Protein Kinases; Lovastatin; Mice; Mice, Nude; Neoplasm Transplantation; Transplantation, Heterologous | 2012 |
The association of manganese superoxide dismutase expression in Barrett's esophageal progression with MnTBAP and curcumin oil therapy.
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 | 2012 |
Curcumin induces cell death in esophageal cancer cells through modulating Notch signaling.
Curcumin inhibits the growth of esophageal cancer cell lines; however, the mechanism of action is not well understood. It is becoming increasingly clear that aberrant activation of Notch signaling has been associated with the development of esophageal cancer. Here, we have determined that curcumin inhibits esophageal cancer growth via a mechanism mediated through the Notch signaling pathway.. In this study, we show that curcumin treatment resulted in a dose and time dependent inhibition of proliferation and colony formation in esophageal cancer cell lines. Furthermore, curcumin treatment induced apoptosis through caspase 3 activation, confirmed by an increase in the ratio of Bax to Bcl2. Cell cycle analysis demonstrated that curcumin treatment induced cell death and down regulated cyclin D1 levels. Curcumin treatment also resulted in reduced number and size of esophagospheres. Furthermore, curcumin treatment led to reduced Notch-1 activation, expression of Jagged-1 and its downstream target Hes-1. This reduction in Notch-1 activation was determined to be due to the down-regulation of critical components of the γ-secretase complex proteins such as Presenilin 1 and Nicastrin. The combination of a known γ-secretase inhibitor DAPT and curcumin further decreased proliferation and induced apoptosis in esophageal cancer cells. Finally, curcumin treatment down-regulate the expressions of Notch-1 specific microRNAs miR-21 and miR-34a, and upregulated tumor suppressor let-7a miRNA.. Curcumin is a potent inhibitor of esophageal cancer growth that targets the Notch-1 activating γ-secretase complex proteins. These data suggest that Notch signaling inhibition is a novel mechanism of action for curcumin during therapeutic intervention in esophageal cancers. Topics: Amyloid Precursor Protein Secretases; Animals; Cell Death; Cell Line, Tumor; Curcumin; Dipeptides; Down-Regulation; Drug Screening Assays, Antitumor; Esophageal Neoplasms; Mice; MicroRNAs; Models, Biological; Receptors, Notch; Signal Transduction; Spheroids, Cellular; Tumor Cells, Cultured | 2012 |
Curcumin abrogates bile-induced NF-κB activity and DNA damage in vitro and suppresses NF-κB activity whilst promoting apoptosis in vivo, suggesting chemopreventative potential in Barrett's oesophagus.
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 | 2012 |
Comparison of the effect of p65 siRNA and curcumin in promoting apoptosis in esophageal squamous cell carcinoma cells and in nude mice.
The activation of the NF-κB signaling pathway plays a critical role in carcinogenesis. The role of the NF-κB pathway in esophageal squamous cell carcinoma (ESCC) remains ill-defined. The objective was to detect whether p65siRNA and curcumin could promote ESCC cell apoptosis and increase the sensitivity of ESCC cells to chemotherapeutic drugs by inhibiting the NF-κB signaling pathway, and to compared these two treatments. In the present study, the status of the NF-κB pathway, in the two ESCC cell lines Eca109 and EC9706, was analyzed and the ability of p65 siRNA and curcumin alone or in combination with 5-FU to modulate this pathway in vitro and in vivo was investigated. The results showed that the NF-κB signaling pathway in the ESCC cell lines was constitutively activated. Both p65 siRNA and curcumin mediated suppression of activation of the NF-κB signaling pathway via inhibition of the expression of p65 or IκBα phosphorylation in ESCC cell lines. The cells treated with combination of p65 siRNA or curcumin and 5-FU revealed a lower cell viability and higher apoptosis compared to those treated with 5-FU alone. In a human ESCC xenograft model, p65 siRNA or curcumin and 5-FU alone reduced the tumor volume, respectively, but their combination had the strongest anticancer effects. Curcumin was more effective than p65 siRNA in vitro and in vivo. Overall, our results indicate that the constitutively activated NF-κB signaling pathway plays a crucial role in these two ESCC cell lines and both p65siRNA and curcumin can promote ESCC cell apoptosis and enhance the sensitivity to 5-FU through suppression of the NF-κB signaling pathway. It is still a long time before RNA interference will be used in the clinic. Therefore, curcumin is proved to be useful in the treatment of ESCC as it is a pharmacologically safe compound without side effects. Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Shape; Curcumin; Cytoplasm; Esophageal Neoplasms; Fluorouracil; Gene Knockdown Techniques; Humans; Male; Mice; Mice, Nude; NF-kappa B; RNA Interference; RNA, Small Interfering; Signal Transduction; Transcription Factor RelA; Tumor Burden; Xenograft Model Antitumor Assays | 2012 |
Curcumin potentiates the antitumor effects of 5-FU in treatment of esophageal squamous carcinoma cells through downregulating the activation of NF-κB signaling pathway in vitro and in vivo.
Although constitutive activation of nuclear factor-kappaB (NF-κB) signaling pathway has been reported in multiple different human tumors, the role of NF-κB pathway in esophageal squamous cell carcinoma (ESCC) remains ill-defined. Abundant sources have provided interesting insights into the multiple mechanisms by which curcumin may mediate chemotherapy and chemopreventive effects on cancer. In this study, we first analyzed the status of NF-κB pathway in the two ESCC cell lines Eca109 and EC9706, and then further investigated whether curcumin alone or in combination with 5-fluorouracil (5-FU) could modulate NF-κB pathway in vitro and in vivo. The results showed that NF-κB signaling pathway was constitutively activated in the ESCC cell lines. Curcumin suppressed the activation of NF-κB via the inhibition of IκBα phosphorylation, and downregulated the expressions of Bcl-2 and CyclinD1 in ESCC cell lines. Curcumin combined with 5-FU led to the lower cell viability and higher apoptosis than 5-FU treated alone. In a human ESCC xenograft model, curcumin or 5-FU alone reduced the tumor volume, but their combination had the strongest anticancer effects. Besides, curcumin could also inhibit NF-κB signaling pathway through downregulation of the IκBα phosphorylation and induction of cell apoptosis in vivo. Overall, our results indicated that constitutively activated NF-κB signaling pathway exists in the two ESCC cells and the chemopreventive effects of curcumin were associated with downregulation of NF-κB signaling pathway and its downstream genes. Topics: Animals; Antineoplastic Agents; Apoptosis; Blotting, Western; Carcinoma, Squamous Cell; Cell Line, Tumor; Curcumin; Cyclin D1; Down-Regulation; Drug Synergism; Esophageal Neoplasms; Fluorouracil; Humans; I-kappa B Proteins; Immunohistochemistry; Male; Mice; Mice, Inbred BALB C; Mice, Nude; NF-kappa B; NF-KappaB Inhibitor alpha; Phosphorylation; Proto-Oncogene Proteins c-bcl-2; Signal Transduction; Tumor Burden; Xenograft Model Antitumor Assays | 2012 |
Effects of curcumin on stem-like cells in human esophageal squamous carcinoma cell lines.
Many cancers contain cell subpopulations that display characteristics of stem cells. Because these cancer stem cells (CSCs) appear to provide resistance to chemo-radiation therapy, development of therapeutic agents that target CSCs is essential. Curcumin is a phytochemical agent that is currently used in clinical trials to test its effectiveness against cancer. However, the effect of curcumin on CSCs is not well established. The current study evaluated curcumin-induced cell death in six cancer cell lines derived from human esophageal squamous cell carcinomas. Moreover, these cell lines and the ones established from cells that survived curcumin treatments were characterized.. Cell loss was assayed after TE-1, TE-8, KY-5, KY-10, YES-1, and YES-2 cells were exposed to 20-80 μM curcumin for 30 hrs. Cell lines surviving 40 or 60 μM curcumin were established from these six original lines. The stem cell markers aldehyde dehydrogenase-1A1 (ALDH1A1) and CD44 as well as NF-κB were used to compare CSC-like subpopulations within and among the original lines as well as the curcumin-surviving lines. YES-2 was tested for tumorsphere-forming capabilities. Finally, the surviving lines were treated with 40 and 60 μM curcumin to determine whether their sensitivity was different from the original lines.. The cell loss after curcumin treatment increased in a dose-dependent manner in all cell lines. The percentage of cells remaining after 60 μM curcumin treatment varied from 10.9% to 36.3% across the six lines. The cell lines were heterogeneous with respect to ALDH1A1, NF-κB and CD44 expression. KY-5 and YES-1 were the least sensitive and had the highest number of stem-like cells whereas TE-1 had the lowest. The curcumin-surviving lines showed a significant loss in the high staining ALDH1A1 and CD44 cell populations. Tumorspheres formed from YES-2 but were small and rare in the YES-2 surviving line. The curcumin-surviving lines showed a small but significant decrease in sensitivity to curcumin when compared with the original lines.. Our results suggest that curcumin not only eliminates cancer cells but also targets CSCs. Therefore, curcumin may be an effective compound for treating esophageal and possibly other cancers in which CSCs can cause tumor recurrence. Topics: Aldehyde Dehydrogenase; Carcinoma, Squamous Cell; Cell Line, Tumor; Curcuma; Curcumin; Esophageal Neoplasms; Humans; Hyaluronan Receptors; Neoplastic Stem Cells; NF-kappa B; Phytotherapy; Plant Extracts | 2012 |
[The molecular mechanisms of curcuma wenyujin extract-mediated inhibitory effects on human esophageal carcinoma cells in vitro].
To study the molecular mechanisms of Curcuma Wenyujin extract-mediated inhibitory effects on human esophageal carcinoma cells.. The Curcuma Wenyujin extract was obtained by supercritical carbon dioxide extraction. TE-1 cells were divided into 4 groups after adherence. 100 microL RMPI-1640 culture medium containing 0.1% DMSO was added in Group 1 as the control group. 100 microL 25, 50, and 100 mg/L Curcuma Wenyujin extract complete culture medium was respectively added in the rest 3 groups as the low, middle, and high dose Curcuma Wenyujin extract groups. The effects of different doses of Curcuma Wenyujin extract (25, 50, and 100 mg/L) on the proliferation of human esophageal carcinoma cell line TE-1 in vitro were analyzed by MTT assay. The gene expression profile was identified by cDNA microarrays in esophageal carcinoma TE-1 cells exposed to Curcuma Wenyujin extract for 48 h. The differential expression genes were further analyzed by Gene Ontology function analysis.. Compared with the control group, MTT results showed that Curcuma Wenyujin extract significantly inhibited the proliferation of TE-1 cells in a dose-dependent manner (P<0.05). The expression level of 88 genes changed with significance, including 66 up-regulation genes and 22 down-regulation genes. Gene Ontology analysis indicated the genes coding for proteins was involved in signal transduction (6), cell cycle (8), apoptosis (14), and cell differentiation (10).. The Curcuma Wenyujin extract could inhibit the growth of human esophageal carcinoma cell line TE-1 in vitro. The molecular mechanisms might be associated with regulating genes expressions at multi-levels. Topics: Apoptosis; Carcinoma; Cell Line, Tumor; Cell Proliferation; Curcuma; Esophageal Neoplasms; Gene Expression Regulation, Neoplastic; Humans; Plant Extracts; Transcriptome | 2012 |
Curcumin induces apoptosis-independent death in oesophageal cancer cells.
Oesophageal cancer incidence is increasing and survival rates remain extremely poor. Natural agents with potential for chemoprevention include the phytochemical curcumin (diferuloylmethane). We have examined the effects of curcumin on a panel of oesophageal cancer cell lines.. MTT (3-(4,5-dimethyldiazol-2-yl)-2,5 diphenyl tetrazolium bromide) assays and propidium iodide staining were used to assess viability and DNA content, respectively. Mitotic catastrophe (MC), apoptosis and autophagy were defined by both morphological criteria and markers such as MPM-2, caspase 3 cleavage and monodansylcadaverine (MDC) staining. Cyclin B and poly-ubiquitinated proteins were assessed by western blotting.. Curcumin treatment reduces viability of all cell lines within 24 h of treatment in a 5-50 muM range. Cytotoxicity is associated with accumulation in G2/M cell-cycle phases and distinct chromatin morphology, consistent with MC. Caspase-3 activation was detected in two out of four cell lines, but was a minor event. The addition of a caspase inhibitor zVAD had a marginal or no effect on cell viability, indicating predominance of a non-apoptotic form of cell death. In two cell lines, features of both MC and autophagy were apparent. Curcumin-responsive cells were found to accumulate poly-ubiquitinated proteins and cyclin B, consistent with a disturbance of the ubiquitin-proteasome system. This effect on a key cell-cycle checkpoint regulator may be responsible for the mitotic disturbances and consequent cytotoxicity of this drug.. Curcumin can induce cell death by a mechanism that is not reliant on apoptosis induction, and thus represents a promising anticancer agent for prevention and treatment of oesophageal cancer. Topics: Antineoplastic Agents; Apoptosis; Autophagy; Caspase 3; Cell Cycle; Cell Line, Tumor; Cell Survival; Curcumin; Cyclin B; Cyclin B1; Esophageal Neoplasms; Humans; Mitotic Index; Proteasome Endopeptidase Complex; Ubiquitin | 2009 |
Chemoprotective effects of Curcuma aromatica on esophageal carcinogenesis.
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 | 2009 |
[Curcumin promotes apoptosis of esophageal squamous carcinoma cell lines through inhibition of NF-kappaB signaling pathway].
Activation of NF-kappaB signaling pathway plays a critical role in the initiation and progression of carcinogenesis. However, the role of NF-kappaB pathway in esophageal squamous cell carcinoma (ESCC) has not been fully elucidated. Studies have shown that curcumin possesses anti-infection and anti-oxidation effects. This study was to evaluate whether curcumin could induce apoptosis through inhibition of NF-kappaB signaling pathway in ESCC cells.. Expressions of pIkappaBalpha and Bcl-2 were detected using Western blott after incubation of ESCC cells with curcumin (50 micromol/L) at different time points. Apoptosis and the number of viable ESCC cells were analyzed using flow cytometry and MTT, respectively, after the treatment of curcumin, 5-FU, or the combination of curcumin and 5-FU.. In two ESCC cell lines, EC9706 and Eca109,curcumin inhibited IkappaBalpha phosphorylation and Bcl-2 in a time-dependent manner; curcumin alone increased cell apoptosis (P<0.05), and the effect became more prominent when it was combined with 5-FU (P<0.05); curcumin plus 5-FU exerted a stronger inhibition effect on cell proliferation than curcumin alone (P<0.05) or 5-FU alone (P<0.05).. Curcumin inhibits the phosphorylation of IkappaBalpha, leading to suppression of proliferation, induction of apoptosis and an increase of the sensitivity of ESCC cell lines towards 5-FU. Topics: Antineoplastic Agents; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Proliferation; Curcumin; Esophageal Neoplasms; Fluorouracil; Humans; NF-kappa B; Proto-Oncogene Proteins c-bcl-2; Signal Transduction | 2008 |
Chemopreventive effect of curcumin on N-nitrosomethylbenzylamine-induced esophageal carcinogenesis in rats.
Modifying effects of curcumin (derived from the rhizome of Curcuma longa L.) during the initiation or post-initiation phase of N-nitrosomethylbenzylamine (NMBA)-induced esophageal carcinogenesis were investigated in male F344 rats. Five-week-old rats were divided into 5 groups, and groups 1, 2 and 3 were given intraperitoneal injections of NMBA (0.5 mg / kg body weight / injection 15 times) for 5 weeks from 7 weeks old to induce esophageal neoplasms. Groups 2 and 3 were fed the diet containing 500 ppm curcumin during the initiation and post-initiation phases, respectively. Group 4 was given the diet containing curcumin throughout the experiment, and group 5 was kept on the basal diet alone and served as an untreated control. Incidence and multiplicity of esophageal neoplasms of group 1 (NMBA alone) were 66.7% and 0.83 +/- 0.70, respectively. Those of groups 2 and 3 were significantly less than those of group 1 (39.3%, 0.46 +/- 0.64, P < 0.05; 33.3%, 0.36 +/- 0.56, P < 0.05, respectively). Furthermore, the incidence and multiplicity of esophageal preneoplastic lesions (moderate or severe epithelial dysplasia) of group 2 (57.1%, 0.61 +/- 0.57; 40%, 0.29 +/- 0.46) or 3 (56.7%, 0.67 +/- 0.66; 23.3%, 0.23 +/- 0.43) were less than those of group 1 (100%, 1.67 +/- 0.70; 70.8%, 0.92 +/- 0.72) (P < 0.05). In this experiment, feeding of curcumin significantly decreased the expression of cell proliferation biomarkers (5-bromo-2'-deoxyuridine labeling index) in the non-lesional esophageal epithelium (P < 0.01). These findings indicate that curcumin inhibits NMBA-induced esophageal carcinogenesis when given during the post initiation as well as initiation phase. This inhibition may be related to suppression of the increased cell proliferation induced by NMBA in the esophageal epithelium. Topics: Animals; Anticarcinogenic Agents; Bromodeoxyuridine; Carcinogens; Curcumin; Dimethylnitrosamine; Esophageal Neoplasms; Male; Precancerous Conditions; Rats; Rats, Inbred F344 | 2000 |