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PubMed2001

Mechanisms of cancer chemoprevention by curcumin.

Curcumin is a major component of the Curcuma species, which is commonly used as a yellow coloring and flavoring agent in foods. Curcumin has shown anti-carcinogenic activity in animals as indicated by its ability to block colon tumor initiation by azoxymethane and skin tumor promotion induced by phorbol ester TPA. Recently, curcumin has been considered by oncologists as a potential third generation cancer chemopreventive agent, and clinical trials using it have been carried out in several laboratories. Curcumin possesses anti-inflammatory activity and is a potent inhibitor of reactive oxygen-generating enzymes, such as lipoxygenase/cyclooxygenase, xanthine dehydrogenase/oxidase and inducible nitric oxide synthase. Curcumin is also a potent inhibitor of protein kinase C, EGF-receptor tyrosine kinase and IkappaB kinase. In addition, curcumin inhibits the activation of NFkappaB and the expression of c-jun, c-fos, c-myc and iNOS. It is proposed that curcumin may suppress tumor promotion by blocking signal transduction pathways in the target cells. Curcumin was first biotransformed to dihydrocurcumin and tetrahydrocurcumin, and these compounds were subsequently convened into monoglucuronide conjugates. The experimental results suggest that curcumin-glucuronide, dihydrocurcumin-glucuronide, tetrahydrocurcumin-glucuronide and tetrahydrocurcumin are major metabolites of curcumin in mice.

Animals↗

PubMed2001

Curcumin prevents intravesical tumor implantation of the MBT-2 tumor cell line in C3H mice.

PURPOSE: The development of an effective nontoxic intravesical agent that may be used immediately after bladder tumor resection to prevent the implantation of tumor cells would be a significant clinical advancement. We report the cytotoxic effects of curcumin on bladder tumor cell lines as well as its effects on the intravesical implantation of tumor cells in C3H mice. MATERIALS AND METHODS: UMUC human and MBT-2 mouse bladder cancer lines were incubated with 0 to 100 microM. curcumin in dimethyl sulfoxide for 30 minutes and cell viability was determined by clonal assay. Additional culture dishes were incubated with curcumin and processed for electron microscopy. Using the C3H mice and the MBT2 tumor lines the effects of intravesical curcumin on tumor implantation after bladder injury was studied. The 10 group 1 mice served as nontreatment controls. In the 18 group 2 mice 30 minutes after tumor cell implantation 100 microM. curcumin in 0.1% dimethyl sulfoxide were instilled intravesically for 30 minutes. The 15 group 3 mice served as treatment controls with 0.1% dimethyl sulfoxide or culture medium instilled intravesically for 30 minutes. Animals were sacrificed 7 to 10 days after treatment and the bladder was subjected to histological analysis for tumor. RESULTS: At the 100 microM. dose curcumin was completely lethal to the 2 cell lines on clonal growth assay. Electron microscopy revealed apoptotic bodies after curcumin administration. The tumor implantation rate was 16.7% (3 of 18 mice) in curcumin treated bladders and 73% (11 of 15) in the vehicle control group. CONCLUSIONS: At the 100 microm. concentration curcumin is a potent cytotoxic agent against the MBT and UMUC bladder tumor cell lines. In addition, curcumin effectively inhibits tumor implantation and growth in this murine bladder tumor model.

Animals↗

PubMed2002

[Chemopreventive effect of tea and curcumin on DMBA-induced oral carcinogenesis in hamsters].

0.5% DMBA solution (in mineral oil) was applied topically to the left cheek pouch of male Syrian golden hamsters 3 times per week for 6 weeks. After the last treatment of DMBA, the animals received 0.6% green tea powder as drinking fluid, or 10 mumol curcumin applied topically 3 times per week, or the combination of green tea and curcumin treatment, or no treatment for 18 weeks. The combination of tea and curcumin significantly decreased the oral visible tumor incidence and the squamous cell carcinoma (SCC) incidence. The combination of tea and curcumin also decreased the number of visible tumors and the tumor volume as well as the numbers of SCC, dysplasic lesions, and papillomas respectively. Green tea or curcumin treatment decreased the number of visible tumor, the tumor volume and the number of SCC respectively. Green tea also decreased the number of dysplasic lesions. Curcumin also significantly decreased the SCC incidence. Tea and curcumin, singly or in combination decreased bromodeoxyuridine (BrdU)-labeling index in hyperplasia, dysplasia, and papillomas. Tea alone and in combination with curcumin significantly increased the apoptotic index in dysplasia and SCC. Curcumin alone and in combination with tea inhibited the angiogenesis in papilloma and SCC. The results suggested that green tea and curcumin had inhibitory effects against oral carcinogenesis at the post-initiation stage and such inhibition may be related to the suppression of cell proliferation, induction of apoptosis, and inhibition of angiogenesis.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed2003

Curcumin exhibits antimetastatic properties by modulating integrin receptors, collagenase activity, and expression of Nm23 and E-cadherin.

Curcumin (diferuloyl methane), the major pigment from the rhizome of Curcuma longa L., has been widely studied for its tumor-inhibiting properties. Recent studies indicate that curcumin can modify cell receptor binding, it also affects intracellular signalling reactions. Curcumin-treated B16F10 melanoma cells formed eight-fold fewer lung metastases in C57BL6 mice. In the cell adhesion assays, curcumin-treated cells showed a dose-dependent reduction in their binding to four extracellular matrix (ECM) proteins. The binding to fibronectin, vitronectin, and collagen IV decreased by over 50% in 24 hours, and by 100% after 48 hours of curcumin treatment, it persisted at this level even after 15 days of cultivating cells in curcumin-free medium. Curcumin-treated cells showed a marked reduction in the expression of alpha5beta1 and alpha(v)beta3 integrin receptors. In addition, curcumin treatment inhibited pp125 focal adhesion kinase (FAK), tyrosine phosphorylation of a 120 kD protein, and collagenase activity. Curcumin enhances the expression of antimetastatic proteins, tissue inhibitor metalloproteinase (TIMP)-2, nonmetastatic gene 23 (Nm23), and E-cadherin. In this article we report on the effect of curcumin on the expression of integrin, TIMP-2, Nm23, E-cadherin, adhesion, and metalloproteinase activity.

Animals↗

PubMed2003

Effect of curcumin on galactose-induced cataractogenesis in rats.

PURPOSE: Curcumin, the active principle of turmeric, has been shown to have both antioxidant and hypoglycemic activity in vitro and in vivo. The purpose of this study was to investigate the effect of curcumin on the onset and maturation of galactose induced cataract. METHODS: Sprague-Dawley rats (21 days old) were divided into 5 groups. The control group (A) received an AIN-93 diet, the galactose group (B) received 30% galactose in the diet, the test groups (C and D) received the B group diet plus 0.002% and 0.01% curcumin respectively, and group (E) received the control diet plus 0.01% curcumin, all for a period of 4 weeks. Cataract progression due to galactose feeding was monitored by slit lamp microscope and classified into 4 stages. At the end of the experiment biochemical parameters such as lipid peroxidation, aldose reductase (AR), sorbitol dehydrogenase (SDH), reduced glutathione, protein content, and protein carbonyls were measured in the lens. Advanced glycated end products (AGE) and protein oxidation were measured by AGE and tryptophon fluorescence respectively. Crystallin profile was analyzed by size exclusion chromatography (HPLC). RESULTS: Slit lamp microscope observations indicated that curcumin at 0.002% (group C) delayed the onset and maturation of cataract. In contrast even though there was a slight delay in the onset of cataract at the 0.01% level (group D), maturation of cataract was faster when compared to group B. Biochemical analysis showed that curcumin at the 0.002% level appeared to exert antioxidant and antiglycating effects, as it inhibited lipid peroxidation, AGE-fluorescence, and protein aggregation. Though the reasons for faster onset and maturation of cataract in group D rats was not clear, the data suggested that under hyperglycemic conditions higher levels of curcumin (0.01%) in the diet may increase oxidative stress, AGE formation, and protein aggregation. However, feeding of curcumin to normal rats up to a 0.01% level did not result in any changes in lens morphology or biochemical parameters. CONCLUSIONS: These results suggest that curcumin is effective against galactose-induced cataract only at very low amounts (0.002%) in the diet. On the other hand at and above a 0.01% level curcumin seems to not be beneficial under hyperglycemic conditions, at least with the model of galactose-cataract.

Aldehyde Reductase↗

PubMed2005

[Effect of curcumin on caspase 8- and caspase 9- induced apoptosis of lymphoma Raji cell].

Curcumin is a crucial component of curcuma. Recently more attention has been paid to the effect of curcumin on specific proliferative inhibition and inducing apoptosis of tumor cells. This study was aimed to investigate the anticancer activities of curcumin and its molecular mechanism. Raji cells (lymphoma cell line) were selected as studying targets, peripheral blood mononuclear cells (PBMNC) obtained from healthy donors were separated by Ficoll solution and suspended in RMPI 1640. The inhibition rates of Raji cells and PBMNC after treatment with curcumin at various concentrations and different times were determined by MTT method and were compared. The expressions of caspase 8 and caspase 9 in Raji cells after treatment with curcumin at 25 micromol/L (IC(50)) and for 24 hours were detected by Western blot. The results showed that curcumin could inhibit proliferation of Raji cells in dose-and time-dependent manner. Curcumin could remarkablely enhance the Raji cell apoptosis at 25 micromol/L and 24 hours (P < 0.01), and its effect was dose-dependent and time-selective. Curcumin had no remarkable effect on PBMNC at certain concentrations, which demonstrated that curcumin could selectively inhibit tumor cell proliferation. It is concluded that the expression of caspase 8 and caspase 9 plays an important role in the proliferation and apoptosis of Raji cells, so that curcumin showed inhibitive effect on Raji cells at various concentrations.

Antineoplastic Agents, Phytogenic↗

PubMed1988

Inhibitory effect of curcumin, chlorogenic acid, caffeic acid, and ferulic acid on tumor promotion in mouse skin by 12-O-tetradecanoylphorbol-13-acetate.

The effects of topically applied curcumin, chlorogenic acid, caffeic acid, and ferulic acid on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced epidermal ornithine decarboxylase activity, epidermal DNA synthesis, and the promotion of skin tumors were evaluated in female CD-1 mice. Topical application of 0.5, 1, 3, or 10 mumol of curcumin inhibited by 31, 46, 84, or 98%, respectively, the induction of epidermal ornithine decarboxylase activity by 5 nmol of TPA. In an additional study, the topical application of 10 mumol of curcumin, chlorogenic acid, caffeic acid, or ferulic acid inhibited by 91, 25, 42, or 46%, respectively, the induction of ornithine decarboxylase activity by 5 nmol of TPA. The topical application of 10 mumol of curcumin together with 2 or 5 nmol of TPA inhibited the TPA-dependent stimulation of the incorporation of [3H]-thymidine into epidermal DNA by 49 or 29%, respectively, whereas lower doses of curcumin had little or no effect. Chlorogenic acid, caffeic acid, and ferulic acid were less effective than curcumin as inhibitors of the TPA-dependent stimulation of DNA synthesis. Topical application of 1, 3, or 10 mumol of curcumin together with 5 nmol of TPA twice weekly for 20 weeks to mice previously initiated with 7,12-dimethylbenz[a]anthracene inhibited the number of TPA-induced tumors per mouse by 39, 77, or 98%, respectively. Similar treatment of mice with 10 mumol of chlorogenic acid, caffeic acid, or ferulic acid together with 5 nmol of TPA inhibited the number of TPA-induced tumors per mouse by 60, 28, or 35%, respectively, and higher doses of the phenolic acids caused a more pronounced inhibition of tumor promotion. The possibility that curcumin could inhibit the action of arachidonic acid was evaluated by studying the effect of curcumin on arachidonic acid-induced edema of mouse ears. The topical application of 3 or 10 mumol of curcumin 30 min before the application of 1 mumol of arachidonic acid inhibited arachidonic acid-induced edema by 33 or 80%, respectively.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1997

Synergistic effects of curcumin on all-trans retinoic acid- and 1 alpha,25-dihydroxyvitamin D3-induced differentiation in human promyelocytic leukemia HL-60 cells.

Treatment of human promyelocytic leukemia HL-60 cells with 10 muM curcumin for 48 h inhibited cellular proliferation and induced small increases in differentiation (100-200%) as measured by the proportion of cells that reduced nitroblue tetrazolium (NBT) and expressed Mac-1. Synergistic induction of differentiation as measured by the above markers was observed when 1-10 muM curcumin was combined with 10-100 nM all-trans retinoic acid (RA) or with 100 nM 1 alpha, 25-dihydroxyvitamin D3 (vitamin D3). Cell morphology and flow cytometric studies (with the monocytic surface antigen CD14) indicated that combinations of RA and curcumin stimulated differentiation predominantly to granulocytes whereas combinations of vitamin D3 and curcumin stimulated differentiation predominantly to monocytes. Studies on cell cycle kinetics indicated that treatment of HL-60 cells with a combination of RA and curcumin for 48 or 96 h reduced the proportion of cells in the S phase of the cell cycle and increased the proportion of cells in the G0/G1 phase of the cell cycle to a greater extent than occurred for cells treated with either compound alone. Combinations of vitamin D3 and curcumin did not alter cell cycle kinetics to a greater extent than was observed for either compound alone. Combinations of RA and curcumin or vitamin D3 and curcumin inhibited the proliferation of HL-60 cells to a greater extent than was observed for either compound alone. The results indicate that curcumin is a weak stimulator of differentiation in HL-60 cells and that is has synergistic effects when combined with RA or vitamin D3. Combinations of curcumin and RA have a particularly potent inhibitory effect on the proliferation of HL-60 cells.

Antigens, Differentiation, Myelomonocytic↗

PubMed2006

Differential effects of curcumin on vasoactive factors in the diabetic rat heart.

BACKGROUND: Increased oxidative stress has been associated with the pathogenesis of chronic diabetic complications, including cardiomyopathy. Recent studies indicate that curcumin, a potent antioxidant, may be beneficial in preventing diabetes-induced oxidative stress and subsequent secondary complications. We have investigated the effects of curcumin on the nitric oxide (NO) pathway in cardiac tissues and cultured cells. METHODS: Streptozotocin-induced diabetic rats were treated with curcumin for a period of one month. Heart tissues were then analyzed for endothelial NO synthase (eNOS) and inducible NO synthase (iNOS) mRNA expression. Oxidative protein and DNA damage were assessed by immunohistochemical analysis of nitrotyrosine and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Heart tissues were further subjected to endothelin-1 (ET-1) mRNA expression. In order to further characterize the effects of curcumin, we assayed microvascular endothelial cells (MVECs). Cultured MVECs, exposed either to glucose or glucose and varying concentrations of curcumin, were assessed for alterations of NOS expression and activation of nuclear factor-kappaB (NF-kappaB) and activating protein-1 (AP-1). Oxidative stress and ET-1 expression levels were also assayed. RESULTS: Our results indicate that one month of diabetes causes an upregulation of both eNOS and iNOS mRNA levels, and nitrotyrosine and 8-OHdG immunoreactivity in the heart. Treatment of diabetic rats with curcumin reduced eNOS and iNOS levels in association with reduced oxidative DNA and protein damage. Interestingly, curcumin further increased vasoconstrictor ET-1 in the heart. Exposure of MVECs to high glucose increased both eNOS and iNOS levels and oxidative stress. Curcumin prevented NOS alteration and oxidative stress in a dose-dependent manner which was mediated by nuclear factor-kappaB and activating protein-1. Exposure to curcumin also increased ET-1 levels in the MVECs. CONCLUSION: Our studies indicate the differential effects of curcumin in vasoactive factor expression in the heart and indicate the importance of tissue microenvironment in the treatment of diabetic complications.

Journal Article↗

PubMed2006

Notch-1 down-regulation by curcumin is associated with the inhibition of cell growth and the induction of apoptosis in pancreatic cancer cells.

BACKGROUND: Notch signaling plays a critical role in maintaining the balance between cell proliferation, differentiation, and apoptosis, and thereby may contribute to the development of pancreatic cancer. Therefore, the down-regulation of Notch signaling may be a novel approach for pancreatic cancer therapy. It has been reported that curcumin down-regulates many genes that are known to promote survival and also up-regulates genes that are known promoters of apoptosis in pancreatic cancer cells in vitro. It also has been reported that there is cross-talk between Notch-1 and another major cell growth and apoptotic regulatory pathway, the nuclear factor kappaB (NF-kappaB) pathway, which is down-regulated by both curcumin and reduction of Notch-1 levels. However, to the authors' knowledge to date, no studies have determined whether the down-regulation of Notch-1 signaling, resulting in the inactivation of NF-kappaB activity, contributes to curcumin-induced cell growth inhibition and apoptosis in pancreatic cancer cells. METHODS: The authors used multiple molecular approaches, such as the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, an apoptosis assay, gene transfection, real-time reverse transcriptase-polymerase chain reaction analysis, Western blot analysis, and an electrophoretic mobility shift assay to measure the DNA binding activity of NF-kappaB. RESULTS: Curcumin inhibited cell growth and induced apoptosis in pancreatic cancer cells. Notch-1, Hes-1, and Bcl-XL expression levels concomitantly were down-regulated by curcumin treatment. These results correlated with the inactivation of NF-kappaB activity and increased apoptosis induced by curcumin. The down-regulation of Notch-1 by small-interfering RNA prior to curcumin treatment resulted in enhanced cell growth inhibition and apoptosis. CONCLUSIONS: The current results provide the first demonstration to the authors' knowledge that the Notch-1 signaling pathway is associated mechanistically with NF-kappaB activity during curcumin-induced cell growth inhibition and apoptosis of pancreatic cells. These results suggest that the down-regulation of Notch signaling by curcumin may be a novel strategy for the treatment of patients with pancreatic cancer.

Antineoplastic Agents↗

PubMed2006

Curcumin (diferuloylmethane) inhibits constitutive active NF-kappaB, leading to suppression of cell growth of human T-cell leukemia virus type I-infected T-cell lines and primary adult T-cell leukemia cells.

Adult T-cell leukemia (ATL) is a fatal malignancy of T lymphocytes caused by infection with human T-cell leukemia virus type I (HTLV-I) and remains incurable. Curcumin (diferuloylmethane), the major pigment of the spice turmeric, can be potentially effective by promoting cell apoptosis. Here we examined whether curcumin is effective in the treatment of ATL. Curcumin prevented cell growth of HTLV-I-infected T-cell lines and primary ATL cells but not of normal peripheral blood mononuclear cells. Curcumin induced cell cycle arrest by reducing the expression of cyclin D1, Cdk1 and Cdc25C and apoptosis by reducing the expression of XIAP and survivin. Most of these genes are known to be regulated by NF-kappaB, which plays a critical role in oncogenesis by HTLV-I. Curcumin suppressed constitutive active NF-kappaB of HTLV-I-infected T-cell lines and primary ATL cells by inhibiting phosphorylation of IkappaBalpha. Curcumin also inhibited Tax-induced NF-kappaB transcriptional activity. However, curcumin-induced suppression of cell growth did not correlate with Tax expression level. Curcumin inhibited the growth of HTLV-I-infected T-cell tumors implanted subcutaneously in SCID mice. Our results indicate that curcumin has tumor-suppressive activity against ATL.

Adult↗

PubMed2006

Targeting constitutive and interleukin-6-inducible signal transducers and activators of transcription 3 pathway in head and neck squamous cell carcinoma cells by curcumin (diferuloylmethane).

Numerous reports suggest that interleukin-6 (IL-6) promotes survival and proliferation of tumor cells through the phosphorylation of a cell-signaling protein, signal-transducer-and-activator-of-transcription-3 (STAT3). Constitutive activation of STAT3 in head and neck squamous cell carcinoma (HNSCC) and its role in proliferation of this tumor has been demonstrated. Thus, agents that can suppress STAT3 activation have potential for the treatment of HNSCC. In the present report, we demonstrate that most HNSCC cell lines had constitutively active STAT3 and that curcumin (diferuloylmethane), a pharmacologically safe agent in humans, inhibited STAT3 phosphorylation in a dose- and time-dependent manner. Nuclear translocation of STAT3 was also inhibited by curcumin. The inhibition of STAT3 activation by curcumin was reversible, although even 24 hr after curcumin removal, only partial reversal occurred. Besides inhibiting constitutive expression, curcumin also abrogated the IL-6-induced activation of STAT3 in HNSCC cells. When compared with AG490, a well-characterized JAK2 inhibitor, curcumin was more rapid (30 min vs. 4 hr) and more potent (25 microM vs. 100 microM) inhibitor of STAT3 phosphorylation. Curcumin was also a more potent inhibitor of HNSCC cell proliferation than AG490. Overall, our results demonstrated that curcumin is a potent inhibitor of constitutive and IL-6-induced STAT3 phosphorylation. This mechanism may be at least partially responsible for curcumin's ability to suppress proliferation of HNSCC cells.

Antineoplastic Agents↗

PubMed2006

Curcumin blocks activation of pancreatic stellate cells.

Activated pancreatic stellate cells (PSCs) play a pivotal role in the pathogenesis of pancreatic fibrosis and inflammation. Inhibition of activation and cell functions of PSCs is a potential target for the treatment of pancreatic fibrosis and inflammation. The polyphenol compound curcumin is the yellow pigment in curry, and has anti-inflammatory and anti-fibrotic properties. We here evaluated the effects of curcumin on the activation and cell functions of PSCs. PSCs were isolated from rat pancreas tissue and used in their culture-activated, myofibroblast-like phenotype unless otherwise stated. The effects of curcumin on proliferation, alpha-smooth muscle actin gene expression, monocyte chemoattractant protein (MCP)-1 production, and collagen expression were examined. The effect of curcumin on the activation of freshly isolated cells in culture was also assessed. Curcumin inhibited platelet-derived growth factor (PDGF)-induced proliferation, alpha-smooth muscle actin gene expression, interleukin-1beta- and tumor necrosis factor (TNF)-alpha-induced MCP-1 production, type I collagen production, and expression of type I and type III collagen genes. Curcumin inhibited PDGF-BB-induced cyclin D1 expression and activation of extracellular signal-regulated kinase (ERK). Curcumin inhibited interleukin-1beta- and TNF-alpha-induced activation of activator protein-1 (AP-1) and mitogen-activated protein (MAP) kinases (ERK, c-Jun N-terminal kinase (JNK), and p38 MAP kinase), but not of nuclear factor-kappaB (NF-kappaB). In addition, curcumin inhibited transformation of freshly isolated cells to myofibroblast-like phenotype. In conclusion, curcumin inhibited key cell functions and activation of PSCs.

Actins↗

PubMed2001

Cytoprotective effect of curcumin in human proximal tubule epithelial cells exposed to shiga toxin.

We conducted the following experiments to determine whether curcumin, an antioxidant compound extracted from the spice tumeric, inhibits cell death induced by Shiga toxin (Stx) 1 and 2 in HK-2 cells, a human proximal tubule cell line. Cells were incubated for 24-48 h with Stx1 or Stx2, 0-100 ng/ml. Test media contained either no further additives or 10-50 microM curcumin. Exposure to Stx1 and Stx2, 100 ng/ml, reduced cell viability to approximately 25% of control values after 24 h and 20 microM curcumin restored viability to nearly 75% of control. Cell staining confirmed that Stx1 and Stx2-induced damage in HK-2 cells involved a combination of apoptosis and necrosis. Thus, Stx1 caused apoptosis and necrosis in 12.2 +/- 2.2 and 12.7 +/- 0.9% of HK-2 cells, respectively. Similarly, Stx2 caused apoptosis and necrosis in 13.4 +/- 2.1 and 9.0 +/- 0.5% of HK-2 cells, respectively. Addition of 20 microM curcumin decreased the extent of apoptosis and necrosis to 2.9 +/- 2.0 and 3.8 +/- 0.2%, respectively in the presence of Stx1 and to 3.0 +/- 2.1 and 3.9 +/- 0.3%, respectively, for Stx2 (P < 0.01). Stx-induced apoptosis and its inhibition by curcumin were confirmed by DNA gel electrophoresis and by an assay for fragmentation. The protective effect of curcumin against Stx1 and Stx2-induced injury to HK-2 was not related to its antioxidant properties. Instead, curcumin enhanced expression of heat shock protein 70 (HSP70) in HK-2 cells under control conditions and after exposure to Stx1 or Stx2. No injury was detectable after incubation of LLC-PK(1) or OK cells, non-human proximal tubule cell lines, with Stx1 or Stx2. Thus, curcumin inhibits Stx-induced apoptosis and necrosis in HK-2 cells in vitro. The cytoprotective effect of curcumin against Stx-induced injury in cultured human proximal tubule epithelial cells may be a consequence of increased expression of HSP70.

Animals↗

PubMed1995

Influence of dietary curcumin and cholesterol on the progression of experimentally induced diabetes in albino rat.

Effect of feeding 0.5% curcumin diet or 1% cholesterol diet was examined in albino rats rendered diabetic with streptozotocin injection. Diabetic rats maintained on curcumin diet for 8 weeks excreted comparatively less amounts of albumin, urea, creatinine and inorganic phosphorus. Urinary excretion of the electrolytes sodium and potassium were also significantly lowered under curcumin treatment. Dietary curcumin also partially reversed the abnormalities in plasma albumin, urea, creatine and inorganic phosphorus in diabetic animals. On the other hand, glucose excretion or the fasting sugar level was unaffected by dietary curcumin and so also the body weights were not improved to any significant extent. Diabetic rats fed curcumin diet had a lowered relative liver weight at the end of the study compared to other diabetic groups. Diabetic rats fed a curcumin diet also showed lowered lipid peroxidation in plasma and urine when compared to other diabetic groups. The extent of lipid peroxidation on the other hand, was still higher in cholesterol fed diabetic groups compared to diabetic rats fed with control diet. Thus, the study reveals that curcumin feeding improves the metabolic status in diabetic conditions, despite no effect on hyperglycemic status or the body weights. The mechanism by which curcumin improves this situation is probably by virtue of its hypocholesterolemic influence, antioxidant nature and free radical scavenging property.

Albumins↗

PubMed1982

Anti-inflammatory and irritant activities of curcumin analogues in rats.

The anti-inflammatory activity of curcumin (C), sodium curcuminate (NaC), diacetyl curcumin (DAC), triethyl curcumin (TEC), tetrahydro curcumin (THC) and ferulic acid (FA) was compared with that of phenylbutazone (PB) using the carrageenin-induced rat paw edema and cotton pellet granuloma tests. The rank order of potencies of curcumin analogues and PB in carrageenin-induced inflammation were NaC greater than THC greater than C greater than PB greater than TEC. The curcumin analogues de decreased carrageenin-induced paw edema at low doses, however, at higher doses this effect was partially reversed. FA and DAC were devoid of anti-inflammatory activity. Curcumin analogues were less effective in inhibiting the granulomatous tissue formation. Maximum activity was observed with TEC whereas C, NaC and PB were almost half as effective as TEC. C and NaC possess both anti-inflammatory and irritant properties as was evident from experiments in which drugs were incorporated into carrageenin and the cotton pellets for inducing inflammation. The anti-inflammatory action of NaC is not mediated through release of steroids from the adrenal cortex or inhibition of the biosynthesis of prostaglandins from arachidonic acid. The results of the present study support the rationale for the use of powdered rhizome of tumeric (contains 0.6% of curcumin) for conditions of sprain and inflammation.

Adrenal Cortex Hormones↗

PubMed2006

Curcumin induces apoptosis via inhibition of PI3'-kinase/AKT pathway in acute T cell leukemias.

Curcumin has been shown to possess variety of biological functions including anti-tumor activity. The mechanism by which curcumin inhibit cell proliferation remains poorly understood. In the present report, we investigated the effect of curcumin on the activation of apoptotic pathway in T-cell acute lymphoblastic leukemia (T-ALL) malignant cells. Our data demonstrate that curcumin causes dose dependent suppression of proliferation in several T cell lines. Curcumin treatment causes the de-phosphorylation/inactivation of constitutively active AKT, FOXO transcription factor and GSK3. Curcumin also induces release of cytochrome c accompanied by activation of caspase-3 and PARP cleavage. In addition, zVAD-fmk, a universal inhibitor of caspases, prevents caspase-3 activation and abrogates cell death induced by curcumin treatment. Finally, treatment of T-ALL cells with curcumin down-regulated the expression of inhibitor of apoptosis protein (IAPs). Taken together, our finding suggest that curcumin suppresses constitutively activated targets of PI3'-kinase (AKT, FOXO and GSK3) in T cells leading to the inhibition of proliferation and induction of caspase-dependent apoptosis.

Apoptosis↗

PubMed2005

Mechanism of inhibition of ascites tumor growth in mice by curcumin is mediated by NF-kB and caspase activated DNase.

One of the most clinically relevant biological activities of curcumin is its anti-cancer property, implicating multiple intracellular pathways in the process. In the present report, we investigated the effect of curcumin on the activation of apoptotic and anti-angiogenic pathways in Ehrlich Ascites Tumor (EAT) cells. Treatment with curcumin in vivo resulted in inhibition of proliferation of EAT cells and ascites formation. Further, we demonstrate that the induction of apoptosis in EAT cells showed nuclear condensation, DNA fragmentation and translocation of caspase-activated DNase (CAD) to nucleus upon curcumin treatment. Curcumin-induced apoptosis is mediated through activation of caspase-3, which is specifically inhibited by the caspase-3 inhibitor, Ac-DEVD-CHO. On the other hand, the decreased secretion of ascites by EAT cells is corroborated by reduction in VEGF secretion upon curcumin treatment. Further, CD31 immunohistological staining of peritoneum sections in curcumin-treated mice suggests its efficacy in acting as anti-angiogenic compound in EAT cells by inhibiting proliferation of endothelial cells in mouse peritoneum. However, immunoflurescence studies of NF-kB revealed that the inhibition of nuclear translocation of NF-kB p65, a transcription factor required for VEGF gene expression, in curcumin-treated EAT cells. These results suggest a further possible clinical application of this diet-derived compound curcumin, as both proapoptotic and anti-angiogenic compound in association with conventional chemotherapeutic agents.

Angiogenesis Inhibitors↗