Showing papers on "Curcumin published in 2000"

Plant phenolics decrease intestinal tumors in an animal model of familial adenomatous polyposis

Abstract: Epidemiological studies consistently indicate that consumption of fruits and vegetables lowers cancer risk in humans and suggest that certain dietary constituents may be effective in preventing colon cancer. Plant-derived phenolic compounds manifest many beneficial effects and can potentially inhibit several stages of carcinogenesis in vivo. In this study, we investigated the efficacy of several plant-derived phenolics, including caffeic acid phenethyl ester (CAPE), curcumin, quercetin and rutin, for the prevention of tumors in C57BL/6J-Min/+ (Min/+) mice. These animals bear a germline mutation in the Apc gene and spontaneously develop numerous intestinal adenomas by 15 weeks of age. At a dietary level of 0.15%, CAPE decreased tumor formation in Min/+ mice by 63%. Curcumin induced a similar tumor inhibition. Quercetin and rutin, however, both failed to alter tumor formation at dietary levels of 2%. Examination of intestinal tissue from the treated animals showed that tumor prevention by CAPE and curcumin was associated with increased enterocyte apoptosis and proliferation. CAPE and curcumin also decreased expression of the oncoprotein beta-catenin in the enterocytes of the Min/+ mouse, an observation previously associated with an antitumor effect. These data place the plant phenolics CAPE and curcumin among a growing list of anti-inflammatory agents that suppress Apc-associated intestinal carcinogenesis.

Curcumin-containing diet inhibits diethylnitrosamine-induced murine hepatocarcinogenesis

Abstract: Curcumin has been widely used as a spice and coloring agent in foods. Recently, curcumin was found to possess chemopreventive effects against skin cancer, forestomach cancer, colon cancer and oral cancer in mice. Clinical trials of curcumin for prevention of human cancers are currently ongoing. In this study, we examine the chemopreventive effect of curcumin on murine hepatocarcinogenesis. C3H/HeN mice were injected i.p. with N-diethylnitrosamine (DEN) at the age of 5 weeks. The curcumin group started eating 0.2% curcumin-containing diet 4 days before DEN injection until death. The mice were then serially killed at the scheduled times to examine the development of hepatocellular carcinoma (HCC) and changes in intermediate biological markers. At the age of 42 weeks, the curcumin group, as compared with the control group (DEN alone), had an 81% reduction in multiplicity (0.5 versus 2.57) and a 62% reduction in incidence (38 versus 100%) of development of HCC. A series of intermediate biological markers were examined by western blot. While hepatic tissues obtained from the DEN-treated mice showed a remarkable increase in the levels of p21(ras), PCNA and CDC2 proteins, eating a curcumin-containing diet reversed the levels to normal values. These results indicate that curcumin effectively inhibits DEN-induced hepatocarcinogenesis in the mouse. The underlying mechanisms of the phenomenon and the feasibility of using curcumin in the chemoprevention of human HCC should be further explored.

Curcumin prevents adriamycin nephrotoxicity in rats

Abstract: The present study investigated the effect of curcumin on adriamycin (ADR) nephrosis in rats. The results indicate that ADR-induced kidney injury was remarkably prevented by treatment with curcumin. Treatment with curcumin markedly protected against ADR-induced proteinuria, albuminuria, hypoalbuminaemia and hyperlipidaemia. Similarly, curcumin inhibited ADR-induced increase in urinary excretion of N-acetyl-beta-D-glucosaminidase (a marker of renal tubular injury), fibronectin and glycosaminoglycan and plasma cholesterol. Curcumin restored renal function in ADR rats, as judged by the increase in GFR. The data also demonstrated that curcumin protected against ADR-induced renal injury by suppressing oxidative stress and increasing kidney glutathione content and glutathione peroxidase activity. In like manner, curcumin abolished ADR-stimulated kidney microsomal and mitochondrial lipid peroxidation. These data suggest that administration of curcumin is a promising approach in the treatment of nephrosis caused by ADR.

Recent studies on the biofunctions and biotransformations of curcumin.

Abstract: Curcumin is a major component of 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. 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. Subsequently, curcumin inhibits the activation of NFkappaB and the expressions of c-jun, c-fos, c-myc and iNOS. It is proposed that curcumin may suppress tumor promotion through blocking signal transduction pathways in the target cells. Curcumin was first biotransformed to dihydrocurcumin and tetrahydrocurcumin and that these compounds subsequently were converted to monoglucuronide conjugates. These results suggest that curcumin-glucuronide, dihydro-curcumin-glucuronide, tetrahydrocurcumin-glucuronide and tetrahydrocurcumin are major metabolites of curcumin in mice.

Curcumin inhibition of bleomycin-induced pulmonary fibrosis in rats

Abstract: Curcumin, an anti-inflammatory, antioxidant, was evaluated for its ability to suppress bleomycin (BLM)-induced pulmonary fibrosis in rats. A single intratracheal instillation of BLM (0.75 U 100−1 g, sacrificed 3, 5, 7, 14 and 28 days post-BLM) resulted in significant increases in total cell numbers, total protein, and angiotensin-converting enzyme (ACE), and alkaline phosphatase (AKP) activities in bronchoalveolar lavage fluid. Animals with fibrosis had a significant increase in lung hydroxyproline content. Alveolar macrophages from BLM-administered rats elaborated significant increases in tumour necrosis factor (TNF)-α release, and superoxide and nitric oxide production in culture medium. Interestingly, oral administration of curcumin (300 mg kg−1 10 days before and daily thereafter throughout the experimental time period) inhibited BLM-induced increases in total cell counts and biomarkers of inflammatory responses in BALF. In addition, curcumin significantly reduced the total lung hydroxyproline in BLM rats. Furthermore, curcumin remarkably suppressed the BLM-induced alveolar macrophage production of TNF-α, superoxide and nitric oxide. These findings suggest curcumin as a potent anti-inflammatory and anti-fibrotic agent against BLM-induced pulmonary fibrosis in rats. British Journal of Pharmacology (2000) 131, 169–172; doi:10.1038/sj.bjp.0703578

The inhibitory effect of curcumin, genistein, quercetin and cisplatin on the growth of oral cancer cells in vitro.

Abstract: Epidemiological evidence indicates that plant derived flavonoids and other phenolic antioxidants protect against heart disease and cancer In the current investigation utilizing human oral squamous carcinoma cell line (SCC-25), we have evaluated the potency of three different plant phenolics, viz, curcumin, genistein and quercetin in comparison with that of cisplatin on growth and proliferation of SCC-25 Test agents were dissolved in DMSO and incubated in triplicates in 25 cm2 flasks in DMEM- HAM's F-12 (50:50)supplemented with 10% calf serum and antibiotics in an atmosphere 5% CO2 in air for 72 hours cell growth was determined by counting the number of cells in a hemocytometer Cell proliferation was determined by measuring DNA synthesis by the incorporation of [3H]-thymidine in nuclear DNA Cisplatin (01, 10, 100 microM) and curcumin (01, 10, 100 microM) induced significant dose-dependent inhibition in both cell growth as well as cell proliferation Genistein and quercetin (10, 100, 1000 microM) had biphasic effect, depending on their concentrations, on cell growth as well as cell proliferation Based on these findings, it is concluded that curcumin is considerably more potent than genistein and quercetin, but cisplatin is five fold more potent than curcumin in inhibition of growth and DNA synthesis in SCC-25

Curcumin inhibits lipoxygenase by binding to its central cavity: theoretical and X-ray evidence.

Abstract: Many lipoxygenase inhibitors including curcumin are currently being studied for their anti-carcinogenic properties. Curcumin is a naturally occurring polyphenolic phytochemical isolated from the powdered rhizome of the plant Curcuma longa that possesses anti-inflammatory properties and inhibits cancer formation in mice. Recently it was shown that the soybean lipoxygenase L1 catalyzed the oxygenation of curcumin and that curcumin can act as a lipoxygenase substrate. In the current study, we investigated the fate of curcumin when used as a soybean lipoxygenase L3 substrate. By use of X-ray diffraction and mass spectrometry, we found an unoccupied electron mass that appears to be an unusual degradation product of curcumin (4-hydroxyperoxy-2-methoxyphenol) located near the soybean L3 catalytic site. Understanding how curcumin inhibits lipoxygenase may help in the development of novel anti-cancer drugs used for treatment where lipoxygenases are involved.

Therapeutic potential of curcumin in human prostate cancer-I. curcumin induces apoptosis in both androgen-dependent and androgen-independent prostate cancer cells.

Abstract: In an effort to find an alternative nontoxic means of inducing the apoptosis potential in both androgen-dependent and hormone refractory prostate cancer cells, attention was focused on curcumin (turmeric), traditionally used in medicine and cuisine in India and other south-east Asian countries. The results indicate that curcumin is a novel and potent inducer of apoptosis in both androgen-dependent and androgen-independent prostate cancer cells. This was accomplished by down-regulating apoptosis suppressor proteins and other crucial proteins such as the androgen receptor. It is concluded that curcumin may provide an alternative, nontoxic modality by which the clinician may prevent the progression of prostate cancer to its hormone refractory state or to treat advanced prostate cancer by forcing them to undergo apoptosis. Prostate Cancer and Prostatic Diseases (2000) 3, 84-93

Inhibitory effects of curcumin and capsaicin on phorbol ester‐induced activation of eukaryotic transcription factors, NF‐κB and AP‐1

Abstract: Recently, considerable attention has been focused on identifying dietary and medicinal phytochemicals that can inhibit, retard or reverse the multi-stage carcinogenesis. Spices and herbs contain phenolic substances with potent antioxidative and chemopreventive properties. Curcumin, a yellow colouring agent from turmeric and capsaicin, a pungent principle of red pepper exhibit profound anticarcinogenic and antimutagenic activities. Two well-defined eukaryotic transcription factors, nuclear factor-kappa B (NF-kappaB) and activator protein 1 (AP-1) have been implicated in pathogenesis of many human diseases including cancer. These transcription factors are known to be activated by a wide array of external stimuli, such as tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), tumor necrosis factor, reactive oxygen species, bacterial lipopolysaccharide, and ultraviolet. In the present study, we found that topical application of TPA onto dorsal skin of female ICR mice resulted in marked activation of epidermal NF-kappaB and AP-1. Curcumin and capsaicin, when topically applied prior to TPA, significantly attenuated TPA-induced activation of each transcription factor in mouse skin. Likewise, both compounds inhibited NF-kappaB and AP-1 activation in cultured human promyelocytic leukemia (HL-60) cells stimulated with TPA. Based on these findings, it is likely that curcumin and capsaicin exert anti-tumor promotional effects through suppression of the tumor promoter-induced activation of transcription factors, NF-kappaB and AP-1.

Isolation of Curcumin from Turmeric

Abstract: Turmeric, the dried yellow rhizome of Curcuma longa, is a common oriental spice that gives curry dishes their characteristic yellowish color and is used in Indian and Thai cooking. The active ingredient in turmeric is curcumin, which is approximately 2% by weight of the root of turmeric. We have developed two simple procedures for isolation of curcumin from turmeric, making this a new and interesting natural product isolation experiment.

Therapeutic potential of curcumin in human prostate cancer. II. Curcumin inhibits tyrosine kinase activity of epidermal growth factor receptor and depletes the protein.

Abstract: Purpose In a search for alternative and preventive therapies for prostate cancer, attention was focused on the ways in which curcumin (Turmeric), used in food and medicine in India for centuries, could interfere with the growth factor signaling pathways in both androgen-dependent and androgen-independent prostate cancer cells, as exemplified by the epidermal growth factor receptor (EGF-R) signaling Materials and methods The androgen-sensitive LNCaP and androgen-insensitive PC-3 cell lines were grown in 5 to 50 microM curcumin and analyzed for EGF-R protein by Western blotting and for EGF-R tyrosine kinase activity Results Curcumin was a potent inhibitor of EGF-R signaling, and it accomplished this effect by three different means (1) down regulating the EGF-R protein; (2) inhibiting the intrinsic EGF-R tyrosine kinase activity; and (3) inhibiting the ligand-induced activation of the EGF-R Conclusions These results, taken together with our previous results that curcumin can induce apoptosis in both androgen-dependent and androgen-independent prostate cancer cells, support our view that curcumin may be a novel modality by which one can interfere with the signal transduction pathways of the prostate cancer cell and prevent it from progressing to its hormone-refractory state

Curcumin and curcuminoid inhibition of angiogenesis

Abstract: Methods for treating diseases or disorders of the skin which are characterized by angiogenesis have been developed using curcumin and curcumin analogs. Based on the results obtained with curcumin, it has been determined that other angiogenesis inhibitors can also be used to treat these skin disorders. It has further been discovered that curcumin acts to inhibit angiogenesis in part by inhibition of basic fibroblast growth factor (bFGF), and thereby provides a means for treating other disorders characterized by elevated levels of bFGF, such as bladder cancer, using curcumin and other analogues which also inhibit bFGF. Representative skin disorders to be treated include the malignant diseases angiosarcoma, hemangioendothelioma, basal cell carcinoma, squamous cell carcinoma, malignant melanoma and Karposi's sarcoma, and the non-malignant diseases or conditions including psoriasis, lymphangiogenesis, hemangioma of childhood, Sturge-Weber syndrome, verruca vulgaris, neurofibromatosis, tuberous sclerosis, pyogenic granulomas, recessive dystrophic epidermolysis bullosa, venous ulcers, acne, rosacea, eczema, molluscum contagious, seborrheic keratosis, and actinic keratosis.

Method for using soluble curcumin to inhibit phosphorylase kinase in inflammatory diseases

Abstract: The compound curcumin, derived from turmeric, inhibits phosphorylase kinase and, by doing so, exhibits a number of physiological effects related to the control of inflammation and cellular proliferation However, curcumin is effective only when in solution Curcumin is almost completely insoluble in water or in oils, but is soluble in alcohols Accordingly, a method for treating inflammation in a mammal comprising administering curcumin in a solution containing at least one alcohol to a mammal to detectably inhibit the activity of phosphorylase kinase in the blood of the mammal or in a tissue of the mammal The alcohol is preferably ethanol, 1-propanol, or 2-propanol; most preferably, it is ethanol Instead of curcumin, a curcumin derivative or curcuminoid can be administered The method can further comprise the administration of at least one additional compound that can be: (1) vitamin D3 and vitamin D3 analogues; (2) vitamin A, vitamin A derivatives, and vitamin A analogues; (3) a calmodulin inhibitor; (4) an anti-inflammatory drug; (5) a calcium channel blocker; (6) a H1 or H2 histamine blocker; (7) an antioxidant; (8) a polyphenolic compound; (9) a monoterpene; (10) genistein; (11) a soybean derived lectin; and (12) dehydrozingerone Another aspect of the present invention is a pharmaceutical composition comprising curcumin, a curcuminoid, or a curcumin derivative in a solution containing at least one alcohol, at least one additional compound as described above, and a pharmaceutically acceptable carrier

Curcumin analogs with anti-tumor and anti-angiogenic properties

Abstract: The present invention is directed to curcumin analogs exhibiting anti-tumor and anti-angiogenic properties, pharmaceutical formulations including such compounds and methods of using such compounds.

Effect of curcumin on the apoptosis of rodent and human nonproliferating and proliferating lymphoid cells.

Abstract: Curcumin, a major active component of turmeric, has been recognized as an anticarcinogenic agent because of its propensity to induce apoptosis in vivo and in vitro. Previously, we showed that curcumin protects cells against oligonucleosomal DNA fragmentation and induces a novel apoptosis-like pathway in Jurkat cells (Piwocka et al. Exp Cell Res 249, 299-307, 1999). Here, we have studied the ability of curcumin to induce cell death in other human and rodent transformed as well as normal cells. Normal cells were quiescent or stimulated to proliferate. We showed that 50 μM pigment is able to induce cell death in all studied cells, but cell death symptoms varied for different cells. All the cells died as assessed by the TdT-mediated UTP nick end labeling method or trypan blue exclusion test. No one type of cells showed oligonucleosomal DNA fragmentation (DNA "ladder") due to curcumin action, although in HL-60 cells, we were able to observe sub-G1 formation and caspase-3 activation. Together, these data showed...

Genistein and Curcumin Block TGF-β1-Induced u-PA Expression and Migratory and Invasive Phenotype in Mouse Epidermal Keratinocytes

Abstract: Transforming growth factor-β1 (TGF-β1) stimulates migration/invasion of mouse transformed keratinocytes and increases urokinase (u-PA) expression/secretion. In this report, we analyzed the biological behavior of two naturally occurring inhibitors of protein tyrosine kinases, genistein and curcumin, that could abrogate the enhancement of u-PA levels induced by TGF-β1 in transformed keratinocytes. Our results showed that genistein and curcumin blocked this response in a dose-dependent manner and also inhibited the TGF-β1-induced synthesis of fibronectin, an early responsive gene to the growth factor. Both compounds also reduced TGF-β1-stimulated cell migration and invasiveness. These results suggest that a tyrosine kinase-signaling pathway should be involved in TGF-β1-mediated increased malignancy of transformed keratinocytes and that genistein and curcumin could play an important role in inhibiting tumor progression.