Inhibitory Effect Of Curcumin Research Articles

Curcumin regulates the miR-21/PTEN/Akt pathway and acts in synergy with PD98059 to induce apoptosis of human gastric cancer MGC-803 cells.

ObjectivePD98059 is a potent and selective inhibitor of mitogen-activated protein kinase. Substantial preclinical evidence has shown an anti-tumor effect of curcumin on various solid tumors. This study aimed to investigate whether curcumin synergistically acts with PD98059 in exerting anti-gastric cancer effects.MethodsThe cell counting kit-8 assay was used to detect cell proliferation of the human gastric cancer MGC-803 cell line. Flow cytometry was performed to detect apoptosis. Western blotting was used to detect phosphatase and tensin homolog (PTEN) and phosphorylated Akt (p-Akt) expression levels. Quantitative reverse transcription-polymerase chain reaction was used to determine microRNA-21 (miR-21).ResultsA dose of 5 to 40 µM curcumin inhibited proliferation of MGC-803 cells in a dose- and time-dependent manner. A high dose of curcumin strongly inhibited p-Akt protein expression. With increasing curcumin levels, PTEN expression increased and miR-21 levels decreased. These results suggest that curcumin negatively modulated the miR-21/PTEN/Akt pathway. Moreover, after pretreatment with PD98059, cell apoptosis induced by curcumin was significantly increased. Additionally, the inhibitory effects of curcumin on the miR-21/PTEN/Akt pathway were significantly enhanced.ConclusionPD98059 combined with curcumin may be a potential strategy for managing gastric cancer.

FLT3-specific curcumin micelles enhance activity of curcumin on FLT3-ITD overexpressing MV4-11 leukemic cells

Curcumin, a major active compound in the turmeric rhizome, has many biological properties, especially anti-leukemia activity. The overexpression of FMS-like tyrosine kinase 3 protein with internal tandem duplication (FLT3-ITD) mutation protein was related to the poor prognosis and disease progression of leukemia. In this study, the cytotoxicity and inhibitory effect of curcumin on cell cycle of FLT3-ITD overexpressing MV4-11 leukemic cells were evaluated. Moreover, curcumin polymeric micelles conjugated with FLT3-specific peptide (FLT3-Cur-micelles) were prepared using a film hydration method to increase curcumin solubility and the inhibitory effect on MV4-11 cells was evaluated. Cytotoxicity and cell cycle analysis were performed using an MTT assay and flow cytometry, respectively. Physical properties of FLT3-Cur-micelles, including particle size, size distribution, morphology, and entrapment efficiency (EE), were evaluated. Cellular uptake of the micelles on MV4-11 cells was determined by flow cytometry and fluorescence microscopy. FLT3-Cur-micelles were observed with size less than 50 nm and high EE of >75%. In addition, FLT3-Cur-micelles demonstrated excellent internalization and increased curcumin accumulation in leukemic cells when compared to free curcumin. Furthermore, FLT3-Cur-micelles exhibited a strong cytotoxic effect on MV4-11 cells with IC50 value of 1.1 µM, whereas the blank micelles showed no effect. Furthermore, FLT3-Cur-micelles showed no significant effect on normal human PBMCs with IC50 value >25 µM. In summary, FLT3-Cur-micelles are a promising nanocarrier system for enhancing anti-leukemic activity of curcumin and suitable for further preclinical studies.

The Inhibitory Effect of Curcumin on Ornithine Decarboxylase against Hepatic Carcinoma

Curcumin the active component of turmeric is widely used as an anticancer agent for treating many human cancers. This study aimed at the extraction of curcumin from Curcuma Longa and investigates its therapeutic effect as ornithine decarboxylase (ODC) inhibitor in HepG2 cells. The proliferation of HepG2 cells was carried out by using the MTT assay. In addition, cell cycle analysis was evaluated by using the flow-cytometric technique. Our results showed that curcumin has the ability to inhibit the proliferation of HepG2 cells with IC50 of 24.79 μg/ml and induced G2/M cell cycle arrest. Moreover, it caused an elevation in the intracellular concentration of Ca2+. Moreover, in the curcumin administration the downregulation expression level of ODC and Bcl-2 genes (p ≤ 0.05) was significant found. On the other hand, upregulation in the expression level of P53, Bax, and caspase-3 genes (p ≤ 0.05). This study concluded that curcumin may be considered as a new saving candidate for the future progress of antitumor agents.

Curcumin alleviates DSS-induced colitis via inhibiting NLRP3 inflammsome activation and IL-1β production

BackgroundNLRP3 inflammasome mediates IL-1β maturation, therefore plays a vital role in the development of IBD. Curcumin is known for possessing strong anti-inflammatory property. ObjectiveThe present study was to investigate the protective effects of curcumin on dextran sulfate sodium (DSS)-induced colitis through inhibiting NLRP3 inflammasome activation and IL-1β production. MethodsLPS-primed macrophages were treated with curcumin prior to DSS triggering NLRP3 inflammasome activation, IL-1β secretion and ASC oligomerization were observed. The mechanisms of curcumin in the inhibition of DSS-induced inflammasome activation were explored. Curcumin or caspase-1/NLRP3 inhibitor was administrated respectively in DSS-induced colitis mouse model. The changes of body weight, disease activity index, colon length were measured. Additionally, mature IL-1β and other inflammatory cytokines, MPO activity and histopathological damage were analyzed for the evaluation of colitis severity. ResultsNLRP3 inflammasome activation was dramatically inhibited by curcumin in DSS-stimulated macrophages, as evidenced by decreased IL-1β secretion, less caspase-1 activation and ASC specks. Mechanistically, curcumin prevented DSS-induced K+ efflux, intracellular ROS formation and cathepsin B release, three major cellular events mediating NLRP3 inflammasome activation. In DSS-induced colitis, curcumin administration significantly ameliorated colitis symptoms by reducing weight loss, DAI and colon length shortening. Meanwhile, curcumin significantly decreased the expression of multiple inflammatory cytokines (including mature IL-1β, IL-6, MCP-1), MPO activity, caspase-1 activity as well as histopathological damage. Furthermore, blockage of NLRP3 inflammasome activation in vivo with specific NLRP3 inhibitor abrogated the further inhibitory effect of curcumin on DSS-induced colitis. ConclusionCurcumin could strongly suppress DSS-induced NLRP3 inflammsome activation and alleviate DSS-induced colitis in mice, thus it may be a promising candidate drug in clinical application for IBD therapy.

Curcumin induces apoptosis and inhibits angiogenesis in murine malignant mesothelioma.

Malignant pleural mesothelioma (MPM) is a rare form of cancer that is associated with asbestos exposure. Unfortunately, current therapies have limited efficacy. Previous studies have indicated that curcumin exerts antiproliferative and antitumor effects, and has low toxicity. The present study aimed to evaluate the anticancer effects of curcumin on the RN5 MPM cell line. The inhibitory effects of curcumin on cell viability were determined using the sulforhodamine B assay. In addition, cell cycle progression was analyzed by propidium iodide (PI) staining and flow cytometry, and curcumin-induced apoptosis was measured by Annexin V/PI double staining. The translocation of apoptosis-inducing factor (AIF) was assessed by western blotting and immunofluorescence, and the expression levels of the phosphoinositide 3-kinase (PI3K)-AKT serine/threonine kinase (Akt)-mammalian target of rapamycin (mTOR) signaling pathway proteins and mitochondria-associated proteins were evaluated by western blotting. In vivo antitumor effects were evaluated in a subcutaneous murine model. Briefly, tumors were harvested from the mice, and immunohistochemistry was conducted to evaluate cell proliferation, apoptosis and angiogenesis. The results indicated that curcumin inhibited RN5 cell viability and induced apoptotic cell death. In addition the findings suggested that curcumin-induced cell apoptosis occurred via the mitochondrial pathway, and caspase-independent and AIF-dependent pathways. Further analysis revealed that curcumin may act as a PI3K-Akt-mTOR signaling pathway inhibitor by downregulating PI3K, p-Akt, p-mTOR and p-p70 ribosomal protein S6 kinase. Furthermore, curcumin inhibited tumor angiogenesis in vivo. In conclusion, curcumin may be potent enough to be developed as a novel therapeutic agent for the treatment of MPM.

Curcumin inhibition of the effects of Tip α induced cytokine expression in gastric cancer patients

Helicobacter pylori (H. pylori) is a major risk factor for gastric cancer. TNF-α inducing protein (Tip α) is an inflammatory factor of H. pylori. It can induce inflammatory cytokine secretion via the NF-kB signaling pathway. The aim of this study is to investigate whether curcumin, a natural NF-kB inhibitor, can reverse the effects of Tip α-induced cytokine expression in gastric cancer subjects both in vitro and ex vivo. The inhibitory effects of curcumin on cytokine expression were detected by Real time RT-PCR and ELISA. NF-kB activation was detected by immunocytochemistry and western blotting. Treatment of MKN-1 and KATOIII cell lines with Tip α showed significantly increased levels of TNF-α, IL-6 and IL-8 in a dose-dependent manner. Tip α could significantly upregulate NF-kB nuclear translocation in both time-dependent and dose-dependent manners. Treatment of the cells with curcumin was able to block the effects of Tip α-induced cytokine expression along with NF-kB nuclear translocation. The ex vivo study using the primary culture obtained from tumor samples taken from patients also showed the same pattern with gastric cancer cell lines. This result suggests that curcumin can be used as chemopreventive agent for gastric cancer in H. pylori infected patients.

Curcumin Suppresses IL-1β Secretion and Prevents Inflammation through Inhibition of the NLRP3 Inflammasome.

Turmeric is traditionally used as a spice and coloring in foods. Curcumin is the primary active ingredient in the turmeric, and compelling evidence has shown that it has the ability to inhibit inflammation. However, the mechanism mediating its anti-inflammatory effects are not fully understood. We report that curcumin inhibited caspase-1 activation and IL-1β secretion through suppressing LPS priming and the inflammasome activation pathway in mouse bone marrow-derived macrophages. The inhibitory effect of curcumin on inflammasome activation was specific to the NLRP3, not to the NLRC4 or the AIM2 inflammasomes. Curcumin inhibited the NLRP3 inflammasome by preventing K+ efflux and disturbing the downstream events, including the efficient spatial arrangement of mitochondria, ASC oligomerization, and speckle formation. Reactive oxygen species, autophagy, sirtuin-2, or acetylated α-tubulin was ruled out as the mechanism by which curcumin inhibits the inflammasome. Importantly, in vivo data show that curcumin attenuated IL-1β secretion and prevented high-fat diet-induced insulin resistance in wide-type C57BL/6 mice but not in Nlrp3-deficient mice. Curcumin also repressed monosodium urate crystal-induced peritoneal inflammation in vivo. Taken together, we identified curcumin as a common NLRP3 inflammasome activation inhibitor. Our findings reveal a mechanism through which curcumin represses inflammation and suggest the potential clinical use of curcumin in NLRP3-driven diseases.

Curcumin Suppresses Pro‐Inflammatory Response through Interference of NF‐κB Activation in Human Umbilical Vein Endothelial Cells

Oxidative stress and redox‐sensitive transcription factors are involved in the process of inflammation which plays a central role in the pathophysiology of atherosclerosis. NF‐κB is a redox‐sensitive transcription factor which was activated secondary to excessive mitochondrial ROS production in the endothelium, participating in a various of proinflammatory and prothrombotic reactions in the endothelial cells. In the present study, we found that the production of ROS was induced by IL‐1 β and pretreatment with curcumin could decrease the induction of ROS by IL‐1 β in human umbilical vein endothelial cells (HUVECs). Since atherosclerosis is a chronic inflammatory disease associated with increased oxidative stress in the vascular endothelium, we proposed that the inhibitory effect of curcumin on NF‐κB activation may be due to its antioxidant and anti‐inflammatory properties. We also measured the nuclear translocation of p65 and p50 protein of the NF‐κB family to examined whether the inhibitory effect of curcumin on the cytokine‐induced expression of pro‐inflammatory response is medicated via NF‐κB. Our results indicated that the nuclear translocation of p65 and p50 were induced by IL‐1 β, whereas the pretreatment with curcumin could inhibit the induction of translocation by IL‐1 β in HUVECs. Therefore, we confirmed that curcumin has an anti‐inflammatory effect through the partial interference of NF‐κB activation.Support or Funding InformationThis study was supported by NSC 100‐2313‐B‐309‐003 to A‐C Cheng and NSC 95‐2815‐C‐039‐019‐B to Y‐M Yu.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Inhibitory Effects of Curcumin on the Expression of NorA Efflux Pump and Reduce Antibiotic Resistance in Staphylococcus aureus

Inhibitory Effects of Curcumin on the Expression of NorA Efflux Pump and Reduce Antibiotic Resistance in Staphylococcus aureus

Curcumin induces apoptosis and cell cycle arrest via the activation of reactive oxygen species–independent mitochondrial apoptotic pathway in Smad4 and p53 mutated colon adenocarcinoma HT29 cells

Curcumin is a natural dietary polyphenol compound that has various pharmacological activities such as antiproliferative and cancer-preventive activities on tumor cells. Indeed, the role reactive oxygen species (ROS) generated by curcumin on cell death and cell proliferation inhibition in colon cancer is poorly understood. In the present study, we hypothesized that curcumin-induced ROS may promote apoptosis and cell cycle arrest in colon cancer. To test this hypothesis, the apoptosis-inducing potential and cell cycle inhibition effect of ROS induced by curcumin was investigated in Smd4 and p53 mutated HT-29 colon adenocarcinoma cells. We found that curcumin treatment significantly increased the level of ROS in HT-29 cells in a dose- and time-dependent manner. Furthermore, curcumin treatment markedly decreased the cell viability and proliferation potential of HT-29 cells in a dose- and time-dependent manner. Conversely, generation of ROS and inhibitory effect of curcumin on HT-29 cells were abrogated by N-acetylcysteine treatment. In addition, curcumin treatment did not show any cytotoxic effects on HT-29 cells. Furthermore, curcumin-induced ROS generation caused the DNA fragmentation, chromatin condensation, and cell nuclear shrinkage and significantly increased apoptotic cells in a dose- and time-dependent manner in HT-29 cells. However, pretreatment of N-acetylcysteine inhibited the apoptosis-triggering effect of curcumin-induced ROS in HT-29 cells. In addition, curcumin-induced ROS effectively mediated cell cycle inhibition in HT-29 cells. In conclusion, our data provide the first evidence that curcumin induces ROS independent apoptosis and cell cycle arrest in colon cancer cells that carry mutation on Smad4 and p53.

Anti-neuroinflammatory effect of curcumin on Pam3CSK4-stimulated microglial cells.

Curcumin is the main curcuminoid present in Curcumalonga and it has been previously reported to exhibit a wide range of pharmacological activities. In the present study, the inhibitory effects of curcumin on the inflammatory mediators released by Pam3CSK4-stimulated BV-2 microglial cells were investigated. The production of pro-inflammatory mediators and cytokines, including tumor necrosis factor-α(TNF-α) and prostaglandinE2(PGE2), were measured by enzyme‑linked immunosorbent assay(ELISA). The expression of inflammatory genes, including inducible nitric oxide synthase and cyclooxygenase-2, were further investigated using reverse transcription-quantitative polymerase chain reaction. The effects of curcumin on heme oxygenase-1(HO-1), nuclear factor (erythroid-derived2)-like2(Nrf2), mitogen-activated protein kinase(MAPK) and nuclear factor-κB(NF-κB) signaling pathways were analyzed by western blotting. The results revealed that curcumin dose-dependently inhibited Pam3CSK4-induced nitric oxide, PGE2, and TNF-α secretion. Curcumin suppressed the secretion of inflammatory mediators through an increase in the expression of HO-1. Curcumin induced HO-1 transcription and translation through the Nrf2/antioxidant response element signaling pathway. Inhibitory experiments revealed that HO-1 was required for the anti-inflammatory effects of curcumin. Further mechanistic studies demonstrated that curcumin inhibited neuroinflammation by suppressing NF-κB and MAPK signaling pathways in Pam3CSK4-activated microglial cells. The results of the present study suggest that curcumin may be a novel treatment for neuroinflammation-mediated neurodegenerative disorders.

Curcumin inhibits bladder cancer stem cells by suppressing Sonic Hedgehog pathway

Cancer stem cells (CSCs) is responsible for the recurrence of human cancers. Thus, targeting CSCs is considered to be a valid way for human cancer treatment. Curcumin is a major component of phytochemicals that exerts potent anticancer activities. However, the effect of curcumin on bladder cancer stem cells (BCSCs) remains to be elucidated. In this study, we investigated the mechanism of curcumin suppressing bladder cancer stem cells. In this study, UM-UC-3 and EJ cells were cultured in serum-free medium (SFM) to form cell spheres that was characterized as BCSCs. Then cell spheres were separately treated with different concentrations of curcumin and purmorphamine. Cell cycle analysis were used to determine the percentage of cells in different phases. Western blot and quantitative real-time PCR analysis were used to detect the expression of relative molecules. Immunofluorescence staining analysis were also utilized to measure the protein level of CD44. We found that CSC markers, including CD44, CD133, ALDH1-A1, OCT-4 and Nanog, were obviously highly expressed in cell spheres. Moreover, we observed that curcumin reduced the cell spheres formation, decreased the expression of CSC markers, suppressed cell proliferation and induced cell apoptosis. We also found that curcumin inhibited the activation of Shh pathway, while the inhibitory effects of curcumin on BCSCs could be weakened by upregulation of Sonic Hedgehog (Shh) pathway. Altogether, these data suggested that curcumin inhibited the activities of BCSCs through suppressing Shh pathway, which might be an effective chemopreventive agent for bladder cancer intervention.

Inhibitory effect of curcumin in human endometriosis endometrial cells via downregulation of vascular endothelial growth factor.

Endometriosis, which affects up to 10% of women of reproductive age, is defined as endometrial-like gland and stroma tissue growths outside the uterine cavity. Despite increasing research efforts, there are no current effective treatment methods for this disease, therefore investigations for therapeutic strategies are of primary concern. In preliminary work, the authors demonstrated that curcumin inhibits endometriosis invivo. The present invitro study aimed to investigate the association between endometriotic stromal cells and curcumin and to clarify the underlying mechanism of action. A total of 14patients with endometriosis were enrolled in the present study. The purity of endometrial stromal cell cultures was proven by standard immunofluorescent staining of vimentin. The cell proliferation and curcumin effects on endometrial stromal cells were assessed by the MTT assay and Hematoxylin and Eosin staining. For cell cycle analysis, phase distribution was detected by flow cytometry. Vascular endothelial growth factor (VEGF) protein expression was examined using immunohistochemistry staining. Apoptosis was assessed using Annexin V‑fluorescein isothiocyanate staining. The results indicated that the treatment of curcumin decreased human ectopic and eutopic stromal cell growth. Following treatment with curcumin, human endometriotic stromal cells demonstrated an increased percentage of G1‑phase cells and decreased percentages of S‑phase cells, particularly in the group treated with 50µmol/l curcumin. Treatment with curcumin additionally decreased expression of VEGF. The data provide evidence that curcumin reduces cell survival in human endometriotic stromal cells, and this may be mediated via downregulation of the VEGF signaling pathway.

Inhibitory effects of curcumin on high glucose-induced damages: Implications for alleviating diabetic complications

Hyperglycemia found in diabetes mellitus causes several physiological abnormalities including the formation of advanced glycation end products (AGEs) and oxidative stress. Accumulation of AGEs and elevation of oxidative stress plays major roles in the development of diabetic complications. Adiponectin secreted from adipocytes is known to improve insulin sensitivity and blood glucose level. Curcumin (CCM), a bioactive component of turmeric, has been reported as a potent antioxidant. Present work aimed to elucidate the roles of CCM in high glucose-induced protein glycation and intracellular events in mature adipocytes. The results demonstrated that CCM inhibited the formation of fluorescent AGEs by approximated 52% at 3 weeks of bovine serum albumin (BSA) glycation with glucose. Correspondingly, CCM decreased the levels of fructosamine and α-dicarbonyl compounds during BSA glycation with glucose. These data suggested that CCM might be a new promising anti-glycation agent. Also, CCM reduced high glucose-induced oxidative stress in a dose dependent manner, whereas CCM treatment time-dependently elevated the expression of adiponectin gene in 3T3-L1 adipocytes. The findings from this study suggested the possibility of therapeutic use of CCM for the prevention of diabetic complications and obesity-related diseases.

Curcumin induced autophagy anticancer effects on human lung adenocarcinoma cell line A549

To investigate the anticancer effects of curcumin-induced autophagy and its effects on the human lung adenocarcinoma A549 cell line, inverted phase contrast microscopy was used to observe alterations to the cytomorphology of cells. An MTT assay was used to measure cell viability. Autophagy was detected using acridine orange (AO) staining and 3-methyladenine (3-MA) was used as an autophagy-specific inhibitor. Dose- and time-dependent A549 cell viability inhibition was observed following curcumin treatment. A dose-dependent increase in the red fluorescent structures in A549 cells was identified following curcumin treatment for 48 h through AO staining. In addition, the activation of autophagy was determined through changes in the number of autophagic vesicles (AVs; fluorescent particles) infected with monodansylcadaverine (MDC). The fluorescence intensity and density of AVs in the curcumin-treated groups were higher at 48 h compared with the control group. Finally, the MTT assay demonstrated that the survival rates of the curcumin-treated cells were increased when pretreated with 3-MA for 3 h, indicating that the inhibitory effect of curcumin on A549 cells is reduced following the inhibition of autophagy. Furthermore, AO and MDC staining confirmed that 3-MA does inhibit the induction of autophagy. Thus, it was hypothesized that the induction of autophagy is partially involved in the reduction of cell viability observed following curcumin treatment. The anticancer effects of curcumin on A549 cells can be reduced using autophagy inhibitors. This suggests a possible cancer therapeutic application of curcumin through the activation of autophagy. These findings have improved the understanding of the mechanism underlying the anticancer property of curcumin.

Inhibition effect of curcumin on UVB-induced secretion of pro-inflammatory cytokines from corneal limbus epithelial cells.

To study the effects of curcumin on the secretion of interleukin (IL)-6 and IL-8 by corneal limbus epithelial cells. Human corneal limbus epithelial cells were isolated and cultured from donor eyes and irradiated by UVB at different dosages with or without curcumin. MTT test was used for studying the effects of UVB and curcumin on the cell viability. The role of mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) pathways on the UVB-induced secretion of IL-6 and IL-8 were tested by addition of their inhibitors to the culture with or without UVB-radiation. Levels of various signal pathways, IL-6 and IL-8 in the cells and in the conditioned culture medium were measured by ELISA analysis. UVB at 20 mJ/cm2 or less and curcumin at 20 µmol/L or less did not affect the cell viability of cultured limbus epithelial cells (P>0.05). UVB irradiation at 10 and 20 mJ/cm2 induced a significant increase of secretion of IL-6 and IL-8 and upregulated NF-κB and phosphorylated MAPK pathways of cultured limbus epithelial cells (P<0.05). Various signal pathway inhibitors, including SP600125 (JNK inhibitor), SB203580 (p38 MAPK inhibitor) and BAY11-7082 (NF-κB inhibitor) significantly decreased the UVB-induced secretion of IL-6 and IL-8 secretion (P<0.05). Curcumin at 5-20 µmol/L significantly inhibited UVB-induced secretion of IL-6 and IL-8 by limbus epithelial cells in a dose-dependent manner; while curcumin alone did not affect the secretion of IL-6 and IL-8. The upregulation of NF-κB and MAPK pathways induced by UVB treatment was significantly inhibited by curcumin, suggesting that NF-κB and MAPK pathways are involved in the inhibitory effect of curcumin on UVB-induced production of IL-6 and IL-8. Curcumin may be a promising agent to be explored for the prevention and treatment of pterygium.

Curcumin Suppresses the Activity of Inhibitor-κB Kinase in an in vitro Inflamed Human Intestinal Mucosa Model by S -nitrosylation

In previous study, we found curcumin to possess anti-inflammatory properties in lipopolysaccharide (LPS)-induced macrophage cells due to the involvement of curcumin and S-nitrosylation in the NF-κB pathway. However, the role of curcumin on regulation of NF-κB signaling pathway through S-nitrosylation in an in vitro inflamed human intestinal mucosa model has not yet been elucidated. This study aimed to concern inhibitory effects of curcumin on NF-κB pathway in two type of inflamed human intestinal cells, Caco-2 and HT-29. Western blot presented the protein expression of iNOS can be reduced by treated curcumin with 30 μM for 12h. Consistently, pro-inflammatory cytokines, such as IL-1β, IL-6, TNFα and IFN-γ was also repressed. The results also shows curcumin reduced the amount of nitrite and nitrate in inflamed human intestinal cells, Caco-2 and HT-29, maintained total S-nitrosylation level on proteins. Furthermore, the protection of S-nitrosylation on IKKβ in inflamed Caco-2 and HT-29 cells by curcumin caused the repression of IκB phosphorylation and NF-κB activation. In conclusion, this study verified that curcumin-mediated S-nitrosylation may be as an important regulator for anti-inflammation in an in vitro inflamed human intestinal mucosa model.

The role of autophagy in the curcumin induced proliferation in human laryngeal cancer Hep2 cell

Objective:The aim of this study is to study the effect of 3-methyladenine (3-MA) on the autophagy and apoptosis of human laryngeal cancer Hep 2 cells induced by curcumin. Method:The proliferation of human laryngeal cancer Hep2 cells was observed by MTT assay. The autophagy level was detected by AO acridine orange staining. Annexin VFITC/PI double staining was used to detect the apoptosis of Hep2 cells. The expression of LC3, Beclin1, Bcl-2 and Bax protein were detected by Western blot. Result:MTT assay showed that curcumin inhibited the proliferation of Hep2 cells in a dose/time dependent manner. The apoptosis rate of curcumin combined with 3-MA increased (P<0.05). Acridine orange staining showed that 3-MA combined with curcumin could significantly reduce the autophagy level of laryngeal carcinoma Hep2 cells. The expression of Bcl-2, Bclin-1 and LC3 Ⅱ was decreased, while the expression of Bax protein was increased (P<0.05). Conclusion:Curcumin can induce apoptosis of Hep 2 cells and induce the development of protective autophagy. The inhibitory effect of curcumin on the apoptosis of laryngeal carcinoma Hep2 cell line was significantly enhanced by 3-MA.

Effect of Curcumin on Fatty Acid Synthase Expression and Enzyme Activity in Breast Cancer Cell Line SKBR3

Background: Fatty acid synthase is a multifunctional protein that catalyzes de novo synthesis of long-chain fatty acids. FASN expression is higher in HER2-positive cells, such as SKBR3 and MCF-7/HER2 cells, than in MCF-7 cells, which express lower HER2 levels. Curcumin, a yellow-colored hydrophobic polyphenol derived from the rhizome turmeric, significantly suppressed growth of human breast cancer cells. In this study, we assessed the effect of curcumin on expression and activity of fatty acid synthase in SK-BR-3 breast cancer cells. Objectives: In this study, we decided to determine the effects of Curcumin on Fatty Acid Synthase expression and enzyme activity in breast cancer cell line SKBR3. Methods: We assessed the cytotoxicity effect of curcumin in SK-BR-3 cells by MTT. Apoptosis was performed by flow cytometry. FAS activity was measured by a spectrophotometer at 340 nm of NADPH absorption. Fatty acid synthase gene expression was analyzed by real-time PCR. Results: Curcumin could decrease cell viability and induce apoptosis in SK-BR-3 cells. Curcumin also reduces the enzyme activity and expression of fatty acid synthase. Conclusions: It is possible that inhibitory effects of curcumin on FAS may induce apoptosis in SK-BR-3 breast cancer cells.

Curcumin inhibits urothelial tumor development by suppressing IGF2 and IGF2-mediated PI3K/AKT/mTOR signaling pathway

We have previously reported that curcumin inhibits urothelial tumor development in a rat bladder carcinogenesis model. In this study, we report that curcumin inhibits urothelial tumor development by suppressing IGF2 and IGF2-mediated PI3K/AKT/mTOR signaling pathway. Curcumin inhibits IGF2 expression at the transcriptional level and decreases the phosphorylation levels of IGF1R and IRS-1 in bladder cancer cells and N-methyl-N-nitrosourea (MNU)-induced urothelial tumor tissue. Ectopic expression of IGF2 and IGF1R, but not IGF1, in bladder cancer cells restored this process, suggesting that IGF2 is a target of curcumin. Moreover, introduction of constitutively active AKT1 abolished the inhibitory effect of curcumin on cell proliferation, migration, and restored the phosphorylation levels of 4E-BP1 and S6K1, suggesting that curcumin functions via suppressing IGF2-mediated AKT/mTOR signaling pathway. In summary, our results reveal that suppressing IGF2 and IGF2-mediated PI3K/AKT/mTOR signaling pathway is one of the mechanisms of action of curcumin. Our findings suggest a new therapeutic strategy against human bladder cancer caused by aberrant activation of IGF2, which are useful for translational application of curcumin.