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Results for “Curcumin”

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At least 289 records · Page 16Linked to original sources

PubMed2003

[Analysis of anti-proliferation of curcumin on human breast cancer cells and its mechanism].

OBJECTIVE: To study the suppressive effects of curcumin on breast carcinoma cells and the mechanism. METHODS: Estrogen receptor (ER) positive human breast cancer line MCF-7 and ER negative human breast cancer line MDA-MB-231 were cultured 17-beta estradiol and curcumin were added into the culture. Northern blot hybridization and Western blots were performed to detect the expression of mRNA and protein. The human ERE promoter activity was analyzed by transient transfection with CAT-reporter constructs. Invasion experiments were conducted with a Matrigel invasion chamber. RESULTS: Curcumin inhibit the proliferation in both estrogen receptor (ER) positive MCF-7 cells and ER negative MDA-MB-231 cells. Curcumin's antiproliferative effects are estrogen dependent in ER positive MCF-7 cells. Curcumin inhibits the expression of ER downstream genes including pS2 and TGF-alpha (transforming growth factor-alpha) in ER-positive MCF-7 cells, and this inhibition is also dependent on the presence of estrogen. In addition, curcumin exerts strong anti-invasive effects in vitro which was not estrogen dependent in the ER-negative MDA-MB-231 breast cancer cells. These anti-invasive effects appeared to be mediated through the down-regulation of MMP-2 (matrix metalloproteinase) and the up-regulation of TIMP-1 (tissue inhibitor of metalloproteinase). Curcumin inhibited the transcript levels of two major angiogenesis factors VEGF (vascular endothelial growth factor) and b-FGF (basic fibroblast growth factor) in ER-negative MDA-MB-231 cells. CONCLUSION: Curcumin exerts multiple suppressive effects on breast carcinoma cells;it's mechanism of chemoprevention is pleiotropic.

Antineoplastic Agents↗

PubMed2003

[Study on the effects of curcumin on angiogenesis].

OBJECTIVE: The effects of curcumin on angiogenesis were studied. METHODS: Proliferation of bovine aortic endothelial cells (BAECs) and cells of human cancerous cell line SGC-7901 were measured by MTT colorimetric assay after treated by various concentrations of curcumin. The effects of curcumin on BAECS proliferation promoted by tumor conditioned medium were observed by MTT colorimetric assay. The effects of various concentration of curcumin on the migration of BAECs and migration promoted by tumor conditioned medium were investigated by agorose assay. RESULTS: Curcumin can obviously inhibit the proliferation of BAECs induced by fetal bovine serum (FBS) and tumor conditioned medium. Curcumin can also obviously inhibit the migration of BAECs induced by FBS and tumor conditioned medium. CONCLUSION: Curcumin can inhibit angiogenesis by preventing proliferation and migration of endothelial cells. It also suggestes that curcumin is one kind of specific inhibitors of angiogenesis.

Adenocarcinoma↗

PubMed2004

Curcumin sensitizes prostate cancer cells to tumor necrosis factor-related apoptosis-inducing ligand/Apo2L by inhibiting nuclear factor-kappaB through suppression of IkappaBalpha phosphorylation.

Epidemiologic studies suggest that diet rich in plant-derived foods plays an important role in the prevention of prostate cancer. Curcumin, the yellow pigment in the spice turmeric, has been shown to exhibit chemopreventive and growth inhibitory activities against multiple tumor cell lines. We have shown previously that curcumin and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/Apo2L interact to induce cytotoxicity in the LNCaP prostate cancer cell line. In this study, we investigated the mechanism by which curcumin augments TRAIL-induced cytotoxicity in LNCaP cells. Subtoxic concentrations of the curcumin-TRAIL combination induced strong apoptotic response in LNCaP cells as demonstrated by the binding of Annexin V-FITC and cleavage of procaspase-3. Furthermore, LNCaP cells express constitutively active nuclear factor-kappaB (NF-kappaB), which is inhibited by curcumin. Because NF-kappaB has been shown to mediate resistance to TRAIL-induced apoptosis in tumor cells, we investigated whether there is a relationship between NF-kappaB activation and resistance to TRAIL in LNCaP prostate cancer cells. Pretreatment with curcumin inhibited the activation of NF-kappaB and sensitized LNCaP cells to TRAIL. A similar increase in the sensitivity of LNCaP cells to TRAIL-induced apoptosis was observed following inhibition of NF-kappaB by dominant negative mutant IkappaBalpha, an inhibitor of NF-kappaB. Finally, curcumin was found to inhibit NF-kappaB by blocking phosphorylation of IkappaBalpha. We conclude that NF-kappaB mediates resistance of LNCaP cells to TRAIL and that curcumin enhances the sensitivity of these tumor cells to TRAIL by inhibiting NF-kappaB activation by blocking phosphorylation of IkappaBalpha and its degradation.

Apoptosis↗

PubMed2004

[Effect of curcumin on STAT5 signaling pathway in primary CML cells].

To study the effect of curcumin on signaling pathway of signal transducers and activators of transcription (STAT5) in primary newly-diagnosed chronic myelocytic leukemia (CML) cells, and to explore the clinical significance of curcumin in the treatment of primary CML cells, the cells were randomly divided into 3 groups: normal control group, CML cells group, and curcumin group; the cellular proliferation was assayed by MTT test; the expression of cellular STAT5 mRNA in CML cells was detected by RT-PCR; the activation of STAT5 in CML cell was detected by electrophoretic mobility shift assay (EMSA). The results showed that the cellular proliferation of curcumin group (OD value 0.640 +/- 0.073) was decreased, as compared with that of the CML cells group (OD value 0.856 +/- 0.083, P <0.01). The expression levels of STAT5 mRNA in CML cells group (integral ratio of OD 1.782 +/- 0.156) were significantly greater than that in the normal control group (integral ratio of OD 0.289 +/- 0.025, P <0.01). The expression of STAT5 mRNA in curcumin group (integral ratio of OD 1.398 +/- 0.126) was significantly decreased as compared with that in the CML cells group (P <0.01). The activation of STAT5 was significantly increased in CML cells group (gray value 5323.375 +/- 515.640) as compared with that in the normal control group (gray value 2943.000 +/- 273.377, P <0.01). The activation of STAT5 of curcumin group (gray value 4331.750 +/- 398.035) was significantly decreased as compared with that of CML cells group (P <0.01). It is concluded that the cellular proliferation and the expression of STAT5 mRNA are increased in the primary CML cells. The activation of STAT5 in primary CML cells is markedly enhanced. STAT5 signaling pathway may be involved in the proliferation of primary CML cells. Curcumin can inhibit the cellular proliferation and the expression of STAT5 mRNA, and down-regulate the activation of STAT5 in primary CML cells. Curcumin may be used in treatment of leukemia.

Adult↗

PubMed2004

[Induction of apoptosis in human nasopharyngeal carcinoma cell line CNE-2Z by curcumin].

BACKGROUND & OBJECTIVE: Nasopharyngeal carcinoma (NPC) is a common malignant tumor in southern China. Radiotherapy is a major therapy for NPC in early phase,while proper chemotherapy is necessary for NPC in late phase. Some chemotherapeutic drugs have been used to treat tumors by inducing apoptosis of tumor cells. This study was to investigate effects of curcumin on proliferation,and apoptosis of NPC cell line CNE-2Z. METHODS: CNE-2Z cells were treated with different concentrations of curcumin, inhibition rates of cell proliferation,and IC(50) of curcumin were detected by MTT method. Cell apoptosis was analyzed by flow cytometry (FCM), agarose gel electrophoresis,and Hoechst33258-PI fluorescence staining. RESULTS: Proliferation of CNE-2Z cells was inhibited obviously by curcumin in dose- and time-dependent manners. IC(50) of curcumin to CNE-2Z cells at 24,48,and 72 h were (24.05+/-0.47),(19.20+/-0.17),and (7.35+/-0.50) micromol/L, respectively. After treated with 5,10,and 20 micromol/L of curcumin for 24 h, apoptotic rates of CNE-2Z cells were (4.9+/-3.2)%,(10.7+/-2.7)%, and (14.7+/-0.5)%, respectively. After treated with 10,20 micromol/L of curcumin for 24 h, morphologic changes, such as chromatin shrinkage,nuclear condensation,and chromatin fragmentation,were observed in CNE-2Z cells by fluorescent staining, a fragmented DNA ladder was detected by electrophoresis. CONCLUSION: Curcumin may induce apoptosis, and inhibit proliferation of CNE-2Z cells.

Antineoplastic Agents↗

PubMed2004

[Determination of curcumin in urine by capillary electrophoresis].

The major component of the plant curcuma longa (a widely cultivated tropical plant in Asia and Central America) is curcumin. Curcumin has been reported to have very strong anti-inflammatory, anti-carcinogenic, anti-oxidant, antiallergic, anti-bacterial, and anti-tumor activities. Little is known about the absorption, distribution, and metabolism of curcumin in human beings. The first step in in vivo physiological and pharmacokinetic studies is to develop a method to measure curcumin in body fluid. A rapid capillary electrophoretic (CE) method with diode array detection was established for the determination of curcumin in human urine. It could be rapidly determined within 2.5 min. The optimized experimental conditions were as follows: 15 mmol/L Na2B4O7 as buffer, applied voltage 20 kV, temperature 25 degrees C and detection wavelength 262 nm. The method has been validated and shows good performance with respect to selectivity, reproducibility and limit of detection. Curcumin had good linearity in the range of 10 - 300 mg/L, and the recoveries of curcumin added in urine were more than 96.3% with relative standard deviations (RSDs) less than 2.3%. The method is sensitive, fast and accurate and can be used to determine curcumin in urine.

Curcuma↗

PubMed2004

[Research of anti-proliferation of curcumin on A549 human lung cancer cells and its mechanism].

OBJECTIVE: To investigate the mechanism of anti-tumor effects of curcumin on human lung cancer cell (A549). METHOD: MTT colorimetry method, fluoroscope, FCM combine PI and Annexin V-FITC double pigmentation method and Western blot method were used. RESULT: Under the effect of the curcumin, cell grew against the wall and suspended in the culture liquid, the A549 cell nucleolus were found fragmentated into different size of apoptosis body under fluoroscopy. The cell proliferation were obvious suppressed after treated with different concentration curcumin for 72 hours. The IC50 were 18 micromol/L by using linear regression. The apoptosis induced by curcumin of A549 cell is concentration dependent. With curcumin increased from 5 micromol/L to 30 micromol/L, Annexin-FITC single positive cell (early apoptosis cell) increased from 3.4% to 59.1%. When curcumin concentration reached 40 micromol/L, PI and Annexin V-FITC double positive cell (secondary apoptosis necrosis cell) became major part of cells, and the cell showed G2 phase block. Observed with western blot method, with the increase of curcumin concentration to 10 micromol/L, the expression of PARP increased simultaneously. CONCLUSION: Curcumin can interfere cell growth cycle of A549 cell and suppress cell growth. The suppression effect is concentration dependent. The effect depends not only from the nonspecific cytotoxic but also from induced cell apoptosis.

Adenocarcinoma↗

PubMed2005

Curcumin attenuates diet-induced hypercholesterolemia in rats.

BACKGROUND: Curcumin (a component of turmeric) has long been used as a spice and food-coloring agent. In experimental animals, curcumin has shown anti-diabetic, anti-inflammatory, cytotoxic and anti-oxidant properties. MATERIAL/METHODS: The possible hypolipidemic effect of curcumin was investigated in rats fed a high-cholesterol diet (HCD). The lipid profile and activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were assessed in serum, as well as anti-oxidant parameters in liver tissues. RESULTS: Feeding the animals a high cholesterol diet (HCD) for 7 consecutive days (1 ml 100 g(-1)) resulted in marked hypercholesterolemia, increased serum level of low-density lipoprotein cholesterol (LDL-C), but a decreased serum high-density lipoprotein cholesterol (HDL-C). Curcumin admixed with the diet (0.5% w/w) decreased serum total cholesterol (TC) by about 21% and LDL-C by 42.5%, but it increased serum HDL by 50%. The atherogenic indices (LDL-C/HDL-C and TC/HDL-C) were reduced by 52% and 35%, respectively. Curcumin also decreased the enzyme activities of serum AST and ALT, which were increased in HCD animals. CONCLUSIONS: Curcumin showed an obvious hypocholesterolemic effect that could be due to an effect on cholesterol absorption, degradation or elimination, but not due to an anti-oxidant mechanism. This could be supported by the finding in our study that neither HCD nor curcumin-admixed HCD had any effects on the liver content of glutathione (GSH) or superoxide dismutase (SOD) activity. Thus one could argue that ingestion of curcumin-containing spices in the diet, especially one rich in fats, could have a lipid-lowering effect.

Alanine Transaminase↗

PubMed2005

Modulation of alpha-crystallin chaperone activity in diabetic rat lens by curcumin.

PURPOSE: A decline in the chaperone-like activity of eye lens alpha-crystallin in diabetic conditions has been reported. In this study, we investigated whether curcumin, a dietary antioxidant, can manipulate the chaperone-like activity of alpha-crystallin in diabetic rat lens. METHODS: A group of rats received ip injection of streptozotocin (STZ; 35 mg/kg body weight in buffer) to induce hyperglycemia, while another group of rats received only buffer as vehicle and served as control. STZ-treated rats were assigned to 3 groups and fed either no curcumin or 0.002% or 0.01% curcumin, respectively. Cataract progression due to hyperglycemia was monitored with a slit lamp biomicroscope. At the end of 8 weeks animals were sacrificed and lenses were collected. alphaH- and alphaL-crystallins from a set of pooled lenses in each group were isolated by gel filtration. Chaperone activity, hydrophobicity, and secondary and tertiary structure of alphaH- and alphaL-crystallins were assessed by light scattering/spectroscopic methods. RESULTS: A decrease in chaperone-like activity of alphaH- and alphaL-crystallins was observed in STZ-treated diabetic rats. The declined chaperone-like activity due to hyperglycemia was associated with reduced hydrophobicity and altered secondary and tertiary structure of alphaH- and alphaL-crystallins. Interestingly, alphaH- and alphaL-crystallins isolated from curcumin fed diabetic rat lenses had shown improved chaperone-like activity as compared to alphaH- and alphaL-crystallins from untreated diabetic rat lens. Feeding of curcumin prevented the alterations in hydrophobicity and structural changes due to STZ-induced hyperglycemia. Modulation of functional and structural properties by curcumin was found to be greater with the alphaL-crystallin than alphaH-crystallin. Loss of chaperone activity of alpha-crystallin, particularly alphaL-crystallin, in diabetic rat lens could be attributed at least partly to increased oxidative stress. Being an antioxidant, curcumin feeding has prevented the loss of alpha-crystallin chaperone activity and delayed the progression and maturation of diabetic cataract. CONCLUSIONS: We demonstrate that curcumin, at the levels close to dietary consumption, prevented the loss of chaperone-like activity of alpha-crystallin vis-a-vis cataractogenesis due to diabetes in rat lens.

Animals↗

PubMed2006

[Prophylactic effect of curcumin on hepatic fibrosis and its relationship with activated hepatic stellate cells].

OBJECTIVE: To observe the prophylactic effect of curcumin on hepatic fibrosis and the number, location, apoptosis of activated hepatic stellate cells (HSCs) in the livers and to discuss the relationship between the prophylactic effects and activated HSC. METHODS: A rat model of hepatic fibrosis was established by intraperitoneal injection of carbon tetrachloride. Curcumin doses of 5 mg, 10 mg, 20 mg per 100 gram per 100g of body weight were given to three groups of the model rats. No curcumin was given to one group of the model rats and it served as the control. After eight weeks, all rats were sacrificed and their left liver lobes were examined histopathologically with H.E and Masson stainings. Grades of hepatic fibrosis were evaluated according to the SSS system. Activated HSC was detected by the alpha-SMA immunohistochemistry staining. HSC apoptosis was detected by double-stainings of terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) and desmin immunohistochemistry staining. RESULTS: Degrees (SSS system scores) of hepatic fibrosis in the curcumin groups were all less severe in comparison with those of the control group. Activated HSCs in the livers of the rats of the control group increased significantly compared with that of the treatment groups, and also fewer apoptotic HSCs were detected in the control group. On the contrary, fewer activated HSCs and more apoptotic HSCs were detected in the curcumin groups compared with those of the control group. The degrees of the effects were curcumin dose-dependent. CONCLUSIONS: Curcumin can prevent hepatic fibrosis. It can inhibit activation and proliferation of HSCs and induce HSCs apoptosis, which may be the mechanism(s) contributing to the prophylactic effects of curcumin on hepatic fibrosis.

Animals↗

PubMed2006

Curcumin inhibits telomerase activity in human cancer cell lines.

Curcumin, one of the major components of tumeric, the dried rhizome of Curcuma longa L, has been shown to have anti-proliferating and anti-carcinogenic properties. In this study, we examined the effects of curcumin on cell growth and telomerase activity in human cancer cell lines Bel7402, HL60 and SGC7901. Curcumin (1-32 microM) showed anti-proliferating effects on these cell lines in a dose-dependent manner in vitro, and anti-tumor effects when curcumin (50-200 mg/kg) was orally administered to nude mice transplanted with the cancer cells. When the cells were treated with 1 microM of curcumin for 120 h, apoptotic cells were observed by means of the adridine orange/ethidium bromide staining method, single cell microgel electrophoresis and flow cytometric analysis. On the other hand, suppression of telomerase activity in extracts of the cells treated with 1 microM of curcumin was observed by means of a telomeric repeat amplification protocol - silver staining assay. These results suggest that curcumin could suppress telomerase activity in the cancer cell lines and that the decrease of telomerase expression followed by induction of apoptosis might be involved in the anti-proliferating effect of curcumin.

Animals↗

PubMedDate not supplied

Curcumin-induced cell cycle arrest and apoptosis in human acute promyelocytic leukemia HL-60 cells via MMP changes and caspase-3 activation.

Curcumin (diferuloylmethane), is a natural product derived from the root of the plant Curcuma longa. For centuries, it has been used as a spice and as a herbal medicine in Chinese populations. Curcumin has been shown to inhibit cell proliferation, cell cycle arrest, cyclooxygenase (COX)-1 and -2 expression and apoptosis in several human cancer cell lines. The aim of this investigation was to clarify the mechanisms by which curcumin induced cytotoxicity and apoptosis in human leukemia HL-60 cells. The effects of curcumin on the levels of reactive oxygen species (ROS), Ca+2 production, cyclin E, cdc25c, wee1, Bcl-2, Bax, the changes of mitochondrial membrane potential (MMP), cytochrome c release and the activation of caspase-3 were also investigated in the HL-60 cells. Results of flow cytometry and DAPI staining assays indicated that curcumin induced cytotoxicity and apoptosis in the examined cells. The results from flow cytometry assay indicated that curcumin induced ROS and Ca+2 productions, decreased the levels of MMP and increased the activity of caspase-3, leading to cell apoptosis. Western blot assay also revealed that curcumin increased the levels of Bax and the release of cytochrome c, and decreased the levels of Bcl-2 in the examined cells. The inhibition of caspase-3 activation by z-VAD-fmk (broad-spectrum caspase inhibitor) completely blocked curcumin-induced apoptosis in HL-60 cells.

Apoptosis↗

PubMed1995

Chemoprevention of colon carcinogenesis by dietary curcumin, a naturally occurring plant phenolic compound.

Human epidemiological and laboratory animal model studies have suggested that nonsteroidal antiinflammatory drugs reduce the risk of development of colon cancer and that the inhibition of colon carcinogenesis is mediated through the alteration in cyclooxygenase metabolism of arachidonic acid. Curcumin, which is a naturally occurring compound, is present in turmeric, possesses both antiinflammatory and antioxidant properties, and has been tested for its chemopreventive properties in skin and forestomach carcinogenesis. The present study was designed to investigate the chemopreventive action of dietary curcumin on azoxymethane-induced colon carcinogenesis and also the modulating effect of this agent on the colonic mucosal and tumor phospholipase A2, phospholipase C gamma 1, lipoxygenase, and cyclooxygenase activities in male F344 rats. At 5 weeks of age, groups of animals were fed the control (modified AIN-76A) diet or a diet containing 2000 ppm of curcumin. At 7 weeks of age, all animals, except those in the vehicle (normal saline)-treated groups, were given two weekly s.c. injections of azoxymethane at a dose rate of 15 mg/kg body weight. All groups were continued on their respective dietary regimen until the termination of the experiment at 52 weeks after the carcinogen treatment. Colonic tumors were evaluated histopathologically. Colonic mucosa and tumors were analyzed for phospholipase A2, phospholipase C gamma 1, ex vivo prostaglandin (PG) E2, cyclooxygenase, and lipoxygenase activities. The results indicate that dietary administration of curcumin significantly inhibited incidence of colon adenocarcinomas (P < 0.004) and the multiplicity of invasive (P < 0.015), noninvasive (P < 0.01), and total (invasive plus noninvasive) adenocarcinomas (P < 0.001). Dietary curcumin also significantly suppressed the colon tumor volume by > 57% compared to the control diet. Animals fed the curcumin diet showed decreased activities of colonic mucosal and tumor phospholipase A2 (50%) and phospholipase C gamma 1 (40%) and levels of PGE2 (> 38%). The formation of prostaglandins such as PGE2, PGF2 alpha, PGD2, 6-keto PGF1 alpha, and thromboxane B2 through the cyclooxygenase system and production of 5(S)-, 8(S)-, 12(S)-, and 15(S)-hydroxyeicosatetraenoic acids via the lipoxygenase pathway from arachidonic acid were reduced in colonic mucosa and tumors of animals fed the curcumin diet as compared to control diet. Although the precise mechanism by which curcumin inhibits colon tumorigenesis remains to be elucidated, it is likely that the chemopreventive action, at least in part, may be related to the modulation of arachidonic acid metabolism.

Animals↗

PubMed1997

Induction of the differentiation of HL-60 promyelocytic leukemia cells by curcumin in combination with low levels of vitamin D3.

Previous studies have shown that an antisense phosphorothioate oligonucleotide to the Rel A subunit of NF- kappa B, as well as vitamin E and related antioxidants, significantly enhanced the differentiation of HL-60 leukemia cells when combined with low levels of 1 alpha, 25-dihydroxyvitamin D3 (vitamin D3) an effect accompanied by a marked inhibition of the transcription factor, NF-kappa B. Curcumin, a potent inhibitor of tumor promotion and of tumor cell growth, has also been shown to have antioxidant properties and to inhibit NF-kappa b. to ascertain whether curcumin would also enhance the differentiation of HL-60 leukemia cells produced by vitamin D3, presumably by interfering with NF- kappa B activity, the effects of curcumin on the differentiation of HL-60 cells produced by low levels of vitamin D3 were measured. Curcumin used alone did not produce a significant degree of differentiation of HL-60 cells; however, this agent markedly enhanced the expression of differentiation markers induced by low levels of vitamin D3. Curcumin also increased the differentiation of HL-60 cells when combined with vitamin D analogues (1,25-dihydroxy-16-ene-23-yne vitamin D3 and 1,25-dihydroxy-16-ene vitamin D3) that share the receptor binding properties of vitamin D3, whereas as vitamin D analogue (1,25-dihydroxy-16,23-diene vitamin D3) that caused significant calcium mobilization, but was less effective than vitamin d3 in binding the receptor, did not cause the differentiation of HL-60 cells in the presence or absence of curcumin. Several dietary compounds structurally related to curcumin (i.e., caffeic acid, chlorogenic acid, and ferulic acid) did not increase the differentiation of HL-60 cells produced by vitamin D3. However, the more lipophilic ethyl of ferulic and caffeic acid were capable of inducing the differentiation of HL-60 cells, as well as enhancing the maturation produced by vitamin D3. Curcumin caused a marked reduction in NF-kappa B activity in nuclear extracts of HL-60 cells exposed to this agent in the presence or absence of vitamin D3, supporting the possibility that NF-kappa B may be a factor in the regulation of the state of differentiation of leukemia cells.

Caffeic Acids↗

PubMed1997

The dietary pigment curcumin reduces endothelial tissue factor gene expression by inhibiting binding of AP-1 to the DNA and activation of NF-kappa B.

The natural occurring pigment curcumin, a major component of the spice tumeric, has been described to have antioxidative, anti-tumorpromoting, anti-thrombotic and anti-inflammatory properties. It appears, that the pleiotropic effects of curcumin are at least partly due to inhibition of the transcription factors NF-kappa B and AP-1. This study investigates the effect of curcumin on the TNF alpha induced expression of endothelial Tissue Factor (TF), the central mediator of coagulation known to be controlled by AP-1 and NF-kappa B. When bovine aortic endothelial cells (BAEC) were preincubated in the presence of curcumin, TNF alpha induced TF gene transcription and expression were reduced. Transient transfection studies with TF-promoter plasmids revealed that both, NF-kappa B and AP-1 dependent TF expression, were reduced by curcumin action. The observed inhibitions were due to distinct mechanisms. Curcumin inhibited TNF alpha induced I kappa B alpha degradation and the nuclear import of NF-kappa B. In contrast, inhibition of AP-1 was due to a direct interaction of curcumin with AP-1-binding to its DNA binding motif. Thus, curcumin inhibits NF-kappa B and AP-1 by two different mechanisms and reduces expression of endothelial genes controlled by both transcription factors in vitro.

Animals↗

PubMed2005

Astrocyte production of the chemokine macrophage inflammatory protein-2 is inhibited by the spice principle curcumin at the level of gene transcription.

BACKGROUND: In neuropathological processes associated with neutrophilic infiltrates, such as experimental allergic encephalitis and traumatic injury of the brain, the CXC chemokine, macrophage inflammatory protein-2 (MIP-2) is thought to play a pivotal role in the induction and perpetuation of inflammation in the central nervous system (CNS). The origin of MIP-2 in inflammatory disorders of the brain has not been fully defined but astrocytes appear to be a dominant source of this chemokine.Curcumin is a spice principle in, and constitutes approximately 4 percent of, turmeric. Curcumin's immunomodulating and antioxidant activities suggest that it might be a useful adjunct in the treatment of neurodegenerative illnesses characterized by inflammation. Relatively unexplored, but relevant to its potential therapeutic efficacy in neuroinflammatory syndromes is the effect of curcumin on chemokine production. To examine the possibility that curcumin may influence CNS inflammation by mechanisms distinct from its known anti-oxidant activities, we studied the effect of this spice principle on the synthesis of MIP-2 by astrocytes. METHODS: Primary astrocytes were prepared from neonatal brains of CBA/CaJ mice. The cells were stimulated with lipopolysaccharide in the presence or absence of various amount of curcumin or epigallocatechin gallate. MIP-2 mRNA was analyzed using semi-quantitative PCR and MIP-2 protein production in the culture supernatants was quantified by ELISA. Astrocytes were transfected with a MIP-2 promoter construct, pGL3-MIP-2, and stimulated with lipopolysaccharide in the presence or absence of curcumin. RESULTS: The induction of MIP-2 gene expression and the production of MIP-2 protein were inhibited by curcumin. Curcumin also inhibited lipopolysaccharide-induced transcription of the MIP-2 promoter reporter gene construct in primary astrocytes. However MIP-2 gene induction by lipopolysaccharide was not inhibited by another anti-oxidant, epigallocatechin gallate. CONCLUSION: Our results indicate that curcumin potently inhibits MIP-2 production at the level of gene transcription and offer further support for its potential use in the treatment of inflammatory conditions of the CNS.

Journal Article↗

PubMedDate not supplied

Inhibition of pancreatic and lung adenocarcinoma cell survival by curcumin is associated with increased apoptosis, down-regulation of COX-2 and EGFR and inhibition of Erk1/2 activity.

BACKGROUND: Several studies suggested that curcumin inhibits growth of malignant cells via inhibition of cyclooxygenase-2 (COX-2) activity. Other studies indicated that epidermal growth factor receptor (EGFR) is also inhibited by curcumin in vitro and in vivo. Moreover, recent investigations revealed an intracellular cross-talk between EGFR signaling and the COX-2 pathway. Our aim was to evaluate whether the curcumin inhibitory effect on the survival of cancer cells is associated with simultaneous down-regulation of COX-2 and EGFR and inhibition of Erk1/2 (extra-cellular signal regulated kinase) signaling pathway. MATERIALS AND METHODS: Lung and pancreas adenocarcinoma cell lines co-expressing COX-2 and EGFR (PC-14 and p34, respectively) and those expressing EGFR but deficient in COX-2 (H1299 and Panc-1, respectively) were exposed for 72 h to curcumin (0-50 microM). Cell viability was assessed by the XTT assay. Apoptosis was determined by FACS analysis. COX-2, EGFR, ErbB-2 and p-Erk1/2 expressions were measured by Western blot analysis. RESULTS: Curcumin's inhibitory effect on survival and apoptosis of lung and pancreatic adenocarcinoma cell lines was significantly higher in the COX-2-expressing cells than in the COX-2-deficient cells. In the p34 and PC-14 cells, curcumin decreased COX-2, EGFR and p-Erk1/2 expressions in a dose-dependent manner. However, in the Panc-1 and H1299 cell lines, which did not express COX-2, curcumin did not affect EGFR levels. CONCLUSION: Curcumin co-inhibited COX-2 and EGFR expression and decreased Erk1/2 activity. This inhibition was associated with decreased survival and enhanced induction of apoptosis in lung and pancreatic adenocarcinoma cells.

Adenocarcinoma↗

PubMed1999

Modulatory effects of curcumin on the chromosomal damage induced by doxorubicin in Chinese hamster ovary cells.

Curcumin, a natural phenolic compound, is gaining importance as a free radical scavenger. This study was undertaken to investigate the modulatory effects of curcumin on the chromosomal damage induced by the antitumoral doxorubicin (DXR), a known free radical generator, in Chinese hamster ovary cells in culture. Cells were treated with three concentrations of curcumin (2.5, 5, or 10 microg/ml) and then treated with DXR (1.0 microg/ml) during different phases of the cell cycle. The results show that curcumin induces chromosomal damage in CHO at the highest concentration when compared to the untreated control. Neither treatment with curcumin shows a reduction in the clastogenicity of DXR. Instead, a statistically significant increase in the frequency of chromosomal damage was observed when the middle and the highest concentrations of curcumin were associated with DXR during the G1/S, S, and S/G2 phases of the cell cycle. The results clearly indicate the potentiating effect of curcumin on DXR-induced chromosomal damage.

Animals↗