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PubMed2005

Liposome-encapsulated curcumin: in vitro and in vivo effects on proliferation, apoptosis, signaling, and angiogenesis.

BACKGROUND: Because a role for nuclear factor-kappaB (NF-kappaB) has been implicated in the pathogenesis of pancreatic carcinoma, this transcription factor is a potential target for the treatment of this devastating disease. Curcumin (diferuloylmethane) is a phytochemical with potent NF-kappaB-inhibitory activity. It is pharmacologically safe, but its bioavailability is poor after oral administration. METHODS: The authors encapsulated curcumin in a liposomal delivery system that would allow intravenous administration. They studied the in vitro and in vivo effects of this compound on proliferation, apoptosis, signaling, and angiogenesis using human pancreatic carcinoma cells. NF-kappaB was constitutively active in all human pancreatic carcinoma cell lines evaluated and liposomal curcumin consistently suppressed NF-kappaB binding (electrophoretic mobility gel shift assay) and decreased the expression of NF-kappaB-regulated gene products, including cyclooxygenase-2 (immunoblots) and interleukin-8 (enzyme-linked immunoassay), both of which have been implicated in tumor growth/invasiveness. These in vitro changes were associated with concentration and time-dependent antiproliferative activity (3-[4,5-dimethylthiazol-2-yl]2,5-diphenyltetrazolium bromide assay [MTT assay]) and proapoptotic effects (annexin V/propidium iodide staining [fluorescence-activated cell sorting] and polyadenosine-5'-diphosphate-ribose-polymerase cleavage). RESULTS: The activity of liposomal curcumin was equal to or better than that of free curcumin at equimolar concentrations. In vivo, curcumin suppressed pancreatic carcinoma growth in murine xenograft models and inhibited tumor angiogenesis. CONCLUSIONS: Liposomal curcumin down-regulated the NF-kappaB machinery, suppressed growth, and induced apoptosis of human pancreatic cells in vitro. Antitumor and antiangiogenesis effects were observed in vivo. The experiments in the current study provide a biologic rationale for treatment of patients suffering from pancreatic carcinoma with this nontoxic phytochemical encapsulated in liposomes for systemic delivery.

Angiogenesis Inhibitors↗

PubMed2006

Curcumin inhibits the mammalian target of rapamycin-mediated signaling pathways in cancer cells.

Curcumin (diferuloylmethane), a polyphenol natural product of the plant Curcuma longa, is undergoing early clinical trials as a novel anticancer agent. However, the anticancer mechanism of curcumin remains to be elucidated. Here we show that curcumin inhibited growth of rhabdomyosarcoma cells (Rh1 and Rh30) (IC50 = 2-5 microM) and arrested cells in G1 phase of the cell cycle. Curcumin also induced apoptosis and inhibited the basal or type I insulin-like growth factor-induced motility of the cells. At physiological concentrations (2.5 microM), curcumin rapidly inhibited phosphorylation of the mammalian target of rapamycin (mTOR) and its downstream effector molecules, p70 S6 kinase 1 (S6K1) and eukaryotic initiation factor 4E (eIF4E) binding protein 1 (4E-BP1), in a panel of cell lines (Rh1, Rh30, DU145, MCF-7 and Hela). Curcumin also inhibited phosphorylation of Akt in the cells, but only at high concentrations (>40 microM). The data suggest that curcumin may execute its anticancer activity primarily by blocking mTOR-mediated signaling pathways in the tumor cells.

Adaptor Proteins, Signal Transducing↗

PubMed2005

Curcumin prevents methylglyoxal-induced oxidative stress and apoptosis in mouse embryonic stem cells and blastocysts.

Methylglyoxal (MG) is a reactive dicarbonyl compound endogenously produced mainly from glycolytic intermediates. Elevated MG levels in diabetes patients are believed to contribute to diabetic complications. MG is cytotoxic through induction of apoptosis. Curcumin, the yellow pigment of Curcuma longa, is known to have antioxidant and anti-inflammatory properties. In the present study, we examined the effect of curcumin on apoptotic biochemical events caused by incubation of ESC-B5 cells with MG. Curcumin inhibited the MG-induced DNA fragmentation, caspase-3 activation, cleavage of PARP, mitochondrial cytochrome c release, and JNK activation. Importantly, curcumin also inhibited the MG-stimulated increase of reactive oxygen species (ROS) in these cells. In addition, we demonstrated that curcumin prevented the MG-induced apoptosis of mouse blastocysts isolated from pregnant mice. Moreover, curcumin significantly reduced the MG-mediated impairment of blastocyst development from mouse morulas. The results support the hypothesis that curcumin inhibits MG-induced apoptosis in mouse ESC-B5 cells and blastocysts by blocking ROS formation and subsequent apoptotic biochemical events.

Animals↗

PubMed2002

The chemopreventive compound curcumin is an efficient inhibitor of Epstein-Barr virus BZLF1 transcription in Raji DR-LUC cells.

To characterize the effects of inhibitors of Epstein-Barr virus (EBV) reactivation, we established Raji DR-LUC cells as a new test system. These cells contain the firefly luciferase (LUC) gene under the control of an immediate-early gene promoter (duplicated right region [DR]) of EBV on a self-replicating episome. Luciferase induction thus serves as an intrinsic marker indicative for EBV reactivation from latency. The tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) induced the viral key activator BamH fragment Z left frame 1 (BZLF1) protein ("ZEBRA") in this system, as demonstrated by induction of the BZLF1 protein-responsive DR promoter upstream of the luciferase gene. Conversely, both BZLF1 protein and luciferase induction were inhibited effectively by the chemopreventive agent curcumin. Semiquantitative reverse transcriptase (RT)-polymerase chain reaction (PCR) further demonstrated that the EBV inducers TPA, sodium butyrate, and transforming growth factor-beta (TGF-beta) increased levels of the mRNA of BZLF1 mRNA at 12, 24, and 48 h after treatment in these cells. TPA treatment also induced luciferase mRNA with similar kinetics. Curcumin was found to be highly effective in decreasing TPA-, butyrate-, and TGF-beta-induced levels of BZLF1 mRNA, and of TPA-induced luciferase mRNA, indicating that three major pathways of EBV are inhibited by curcumin. Electrophoretic mobility shift assays (EMSA) showed that activator protein 1 (AP-1) binding to a cognate AP-1 sequence was detected at 6 h and could be blocked by curcumin. Protein binding to the complete BZLF1 promoter ZIII site (ZIIIA+ZIIIB) demonstrated several specific complexes that gave weak signals at 6 h and 12 h but strong signals at 24 h, all of which were reduced after application of curcumin. Autostimulation of BZLF1 mRNA induction through binding to the ZIII site at 24 h was confirmed by antibody-induced supershift analysis. The present results confirm our previous finding that curcumin is an effective agent for inhibition of EBV reactivation in Raji DR-CAT cells (carrying DR-dependent chloramphenicol acetyltransferase), and they show for the first time that curcumin inhibits EBV reactivation mainly through inhibition of BZLF1 gene transcription.

Anticarcinogenic Agents↗

PubMed1995

Curcumin, an anti-tumour promoter and anti-inflammatory agent, inhibits induction of nitric oxide synthase in activated macrophages.

L-Arginine-derived nitric oxide (NO) and its derivatives, such as peroxynitrite and nitrogen dioxide, play a role in inflammation and also possibly in the multistage process of carcinogenesis. We investigated the effect of various non-steroidal anti-inflammatory agents and related compounds on the induction of NO synthase (NOS) in RAW 264.7 macrophages activated with lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma). Low concentrations of curcumin, a potent anti-tumour agent having anti-inflammatory and anti-oxidant properties, inhibited NO production, as measured by the amount of nitrite released into the culture medium in 24 h (IC50 = 6 microM). NOS activity in soluble extracts of macrophages activated for 6-24 h in the presence of curcumin (10 microM) was significantly lower than that of macrophages activated without curcumin. Northern-blot and immunoblotting analyses demonstrated that significantly reduced levels of the mRNA and 130-kDa protein of inducible NOS were expressed in macrophages activated with curcumin, compared to those without curcumin. Inhibition of NOS induction was maximal when curcumin was added together with LPS and IFN-gamma and decreased progressively as the interval between curcumin and LPS/IFN-gamma was increased to 18 h.

Amino Acid Oxidoreductases↗

PubMed1998

Apoptosis-independent alterations in membrane dynamics induced by curcumin.

Curcumin is a well-known natural compound with antiinflammatory properties. Its antiproliferative effect and ability to modulate apoptotic response are considered essential in cancer therapy. The physicochemical properties of curcumin suggest membranous localization, which prompted an investigation of the mechanisms of membrane disturbances evoked by curcumin. We chose the erythrocyte as a convenient model for studying membrane effects of curcumin and showed its nonspecific, apoptosis-independent way of action. Curcumin was found to expand the cell membrane, inducing echinocytosis. Changes in cell shape were accompanied by transient exposure of phosphatidylserine. Membrane asymmetry was recovered by the action of aminophospholipid translocase, which remained active in the presence of curcumin. Lipids rearrangements and drug partitioning caused changes of lipid fluidity. Such nonspecific effects of curcumin on cellular membranes would produce artifacts of apoptosis measurement, since several methods are based on membrane changes.

Adult↗

PubMed1999

Curcumin inhibition of inflammatory cytokine production by human peripheral blood monocytes and alveolar macrophages.

Curcumin, a dietary pigment responsible for the yellow colour of curry, has been used for the treatment of inflammatory diseases and exhibits a variety of pharmacological effects such as anti-inflammatory activity. The mechanism in anti-inflammatory activity of curcumin has been investigated; however, little is known about the effect of curcumin on cytokine production by human peripheral blood monocytes and alveolar macrophages. In the present study, we shed light on the effect of curcumin on inflammatory cytokine production by human peripheral blood monocytes and alveolar macrophages. To this end, we determined the concentrations of interleukin-8 (IL-8), monocyte inflammatory protein-1 (MIP-1alpha), monocyte chemotactic protein-1 (MCP-1), interleukin-1beta (IL-1beta), and tumour necrosis factor-alpha (TNF-alpha) in the culture supernatants from phorbor ester, 4beta phorbor 12beta-myristate-13alpha acetate (PMA)- or lipo-polysaccharide (LPS)-stimulated monocytes and alveolar macrophages in the presence or absence of curcumin. Curcumin inhibited the production of IL-8, MIP-1alpha, MCP-1, IL-1beta, and TNF-alpha by PMA- or LPS-stimulated monocytes and alveolar macrophages in a concentration- and a time-dependent manner. These results show that curcumin exhibits an inhibitory effect on the production of IL-8, MIP-1alpha, MCP-1, IL-1beta, and TNF-alpha by PMA- or LPS-stimulated monocytes and alveolar macrophages.

Adult↗

PubMed2005

Effect of curcumin on immune function of mice.

To investigate the effect of curcumin on immune function of mice, the effect of curcumin was examined on the proliferation of spleen lymphocytes of mice and the function of phagocytosis of peritoneal macrophage by using MTT test and the expression of the nucleoprotein of NFkappaB p65 was determined in spleen lymphocytes by employing Western Blot. Our results showed that curcumin could enhance the phagocytosis of peritoneal macrophages. Lowdose curcumin could upregulate the proliferation of spleen lymphocytes of mice, and highdose curcumin could suppress the proliferation of spleen lymphocytes. Curcumin could suppress the expression of NFkappaB p65. Our study suggested that curcumin can regulate immune function of mice in a dosedependent manner. The possible underlying mechanism might be its ability to suppress the activity of NFkappaB p65.

Adjuvants, Immunologic↗

PubMed2000

The influence of curcumin on the cell cycle of HL-60 cells and contrast study.

The mechanisms of curcumin inhibiting the proliferation of HL-60 cells were investigated. Acute myeloid leukemic cell line HL-60 was studied by using cell culture, NBT reduction, SABC method measuring BrdU incorporation rate, FCM measuring DNA contents and TUNEL method determining apoptotic cell percentage. Curcumin inhibited proliferation of HL-60 cells in a dose- and time-dependent manner. When the HL-60 cells were treated with 25 mumol/L curcumin for 48 h, the inhibitory rate was 60.71% +/- 1.20%. The study on BrdU incorporation rate and the distribution of DNA content and NBT reduction indicated that curcumin arrested the cells in G2/M phase of cell cycle at first, then in G0/G1 phase, the whole cell cycle progression was slowed down and DNA synthesis activities was halted. The arrested cells went to apoptosis instead of differentiation. The comparative study indicated that the ability of curcumin regulating the cell cycle of HL-60 cells was stronger than As2O3 and the acting points of curcumin were not completely consistent with those of VP-16. It was suggested that curcumin was able to regulate, to some extent, the G1/S and G2/M transmit checkpoints and disturb the HL-60 cell cycle to induce apoptosis.

Antineoplastic Agents↗

PubMed2002

The experimental and clinical study on the effect of curcumin on cell cycle proteins and regulating proteins of apoptosis in acute myelogenous leukemia.

To investigate whether the Bcl-2 gene family is involved in modulating mechanism of apoptosis and change of cell cycle protein induced by curcumin in acute myeloid leukemia HL-60 cell line and primary acute myelogenous leukemic cells, the Bcl-2 family member Mcl-1, Bax and Bak and cell cycle proteins including P27kipl, P21wafl, cyclin D3 and pRbp- were selected and their expression detected by SABC immuno-histochemical stain method. The attitude of sub-G1 peak in DNA histogram was determined by FCM. The TUNEL positive cell percentage was identified by terminal deoxynucleotidyl transferase (TdT)-mediated Biotin dUNP end labeling technique. It was found that when HL-60 cells were treated with 25 mumol/L curcumin for 24 h, the expression level of Mcl-1 was down-regulated, but that of Bax and Bak up-regulated time-dependently. There was significant difference in the expression level of Mcl-1, Bax and Bak between the curcumin-treated groups and control group (P < 0.05-0.01). At the same time, curcumin had no effect on progress of cell cycle in primaty acute myelogenous leukemia at newly diagnosis, but could increase the peak of Sub-G1 (P < 0.05), and down-regulate the expression of Mcl-1 and up-regulate the expression of Bax and Bak with the difference being statistically significant. The expression of P27kipl, P21wafl and pRbp- were elevated and that of cyclin D3 decreased in the presence of curcumin. These findings suggested that the Bcl-2 gene family indeed participated in the regulatory process of apoptosis induced by curcumin in HL-60 cells and AML cells. Curcumin can induce apoptosis of primary acute myelogenous leukemic cells and disturb cell cycle progression of HL-60 cells. The mechanism appeared to be mediated by perturbing G0/G1 phases checkpoints which associated with up-regulation of P27kipl, P21wafl and pRbp- expression, and down-regulation of cyclin D3.

Antineoplastic Agents, Phytogenic↗

PubMed2006

Inhibitory effect of curcumin on MDR1 gene expression in patient leukemic cells.

When patients with cancers are treated with chemotherapeutic agents a long time, some of the cancer cells develop the multidrug resistance (MDR) phenotype. MDR cancer cells are characterized by the overexpression of multidrug resistance1(MDR1) gene which encodes P-glycoprotein (Pgp), a surface protein of tumor cells that functions to produce an excessive efflux and thereby an insufficient intracellular concentration of chemotherapeutic agents. A variety of studies have sought potent MDR modulators to decrease MDR1 gene expression in cancer cells. Our previous study has shown that curcumin exhibits characteristics of a MDR modulator in KB-V1 multidrug-resistant cells. The aim of this study was to further investigate the effect of curcumin on MDR1 gene expression in patient leukemic cells. The leukemic cells were collected from 78 childhood leukemia patients admitted at Maharaj Nakorn Chiang Mai Hospital, Chiang Mai, Thailand, in the period from July 2003 to February 2005. There were 61 cases of acute lymphoblastic leukemia (ALL), 14 cases of acute myeloblastic leukemia (AML), and 3 cases of chronic myelocytic leukemia (CML). There were 47 males and 31 females ranging from 1 to 15 years old. Bone marrows were collected. The leukemic cells were separated and cultured in the presence or absence of 10 microM curcumin for 48 hours. MDR1 mRNA levels were determined by RT-PCR. It was found that curcumin reduced MDR1 gene expression in the cells from 33 patients (42%). Curcumin affected the MDR1 gene expression in 5 of 11 relapsed cases (45%), 10 of 26 cases of drug maintenance (38%), 7 of 18 cases of completed treatment (39%), and 11 of 23 cases of new patients (48%). The expression levels of MDR1 gene in leukemic patient cells as compared to that of KB-V1 cells were classified as low level (1-20%) in 5 of 20 cases (25%), medium level (21-60%) in 14 of 32 cases (44%), and high level (61-100%) in 14 of 20 cases (70%). In summary, curcumin decreased MDR1 mRNA level in patient leukemic cells, especially in high level of MDR1 gene groups. Thus, curcumin treatment may provide a lead for clinical treatment of leukemia patients in the future.

Acute Disease↗

PubMed2006

DNA damage in mouse lymphocytes exposed to curcumin and copper.

Dietary polyphenolics, such as curcumin, have shown antioxidant and anti-inflammatory effects. Some antioxidants cause DNA strand breaks in excess of transition metal ions, such as copper. The aim of this study was to evaluate the in vitro effect of curcumin in the presence of increasing concentrations of copper to induce DNA damage in murine leukocytes by the comet assay. Balb-C mouse lymphocytes were exposed to 50 microM curcumin and various concentrations of copper (10 microM, 100 microM and 200 microM). Cellular DNA damage was detected by means of the alkaline comet assay. Our results show that 50 microM curcumin in the presence of 100-200 microM copper induced DNA damage in murine lymphocytes. Curcumin did not inhibit the oxidative DNA damage caused by 50 microM H2O2 in mouse lymphocytes. Moreover, 50 microM curcumin alone was capable of inducing DNA strand breaks under the tested conditions. The increased DNA damage by 50 mM curcumin was observed in the presence of various concentrations of copper, as detected by the alkaline comet assay.

Animals↗

PubMed1999

Interaction of curcumin with human serum albumin--a spectroscopic study.

Curcumin (diferuloyl methane) has a wide range of physiological and pharmacological actions. Curcumin interaction with human serum albumin (HSA) has been followed by fluorescence quenching and circular dichroism (CD) measurements. Based on fluorescence measurements, the equilibrium constant for the interaction is 2.0+/-0.2x10(5) M(-1). Binding of curcumin to HSA induces an extrinsic CD band in the visible region. From the induced CD band measurements, the equilibrium constant has a value of 2.1+/-0.3x10(4) M(-1). Thus, HSA has two kinds of affinity sites for curcumin, one with high affinity and the other with lower affinity. Job's plot indicated a binding stoichiometry of 1:1 for the high-affinity site. The equilibrium constant was invariant with temperature in the range of 15 to 45 degrees C, suggesting the role of hydrophobic interactions in the binding of curcumin to HSA. Curcumin does not change the conformation of the HSA molecule. These measurements have implications in the understanding of the curcumin transport under physiological conditions.

Biological Transport↗

PubMed1996

Action of curcumin on the cytochrome P450-system catalyzing the activation of aflatoxin B1.

Curcumin, in a dose-dependent manner, inhibited the formation of covalent adduct between aflatoxin B1 and DNA, as catalyzed by microsomes or a reconstituted microsomal monooxygenase system. Its effect on the cytochrome P450-system was investigated in the latter system. The inhibition (50%) of aflatoxin B1-DNA adduct formation by curcumin in this system could be reversed by increasing the amount of cytochrome P450 but not by that of NADPH-cytochrome P450 reductase. Curcumin inhibited the reductase activity when measured by the reduction of cytochrome C but not when measured by the reduction of dichlorophenolindophenol, an artificial electron acceptor. These results, as well as the reversal of curcumin-induced inhibition of P450 reductase activity by higher amounts of cytochrome C, indicated a strong affinity of curcumin towards cytochromes. This was further substantiated from the observation that curcumin-pretreated cytochrome P450 had reduced ability to catalyze aflatoxin B1-DNA adduct formation in the reconstituted system. Curcumin, thus, may inhibit chemical carcinogenesis by modulating cytochrome P450 function.

Aflatoxin B1↗

PubMed1994

Curcumin is a non-competitive and selective inhibitor of phosphorylase kinase.

Recently, we reported that curcumin (diferuloylmethane) inhibits the growth of several different kinds of tumor cells. In order to investigate the mechanism of this inhibition, we examined the effects of curcumin on different protein kinases: highly purified protein kinase A (PkA), protein kinase C (PkC), protamine kinase (cPK), phosphorylase kinase (PhK), autophosphorylation-activated protein kinase (AK) and pp60c-src tyrosine kinase. While all kinases tested were inhibited by curcumin, only PhK was completely inhibited at relatively lower concentrations. At around 0.1 mM curcumin, PhK, pp60c-src, PkC, PkA, AK, and cPK were inhibited by 98%, 40%, 15%, 10%, 1%, and 0.5%, respectively. Lineweaver-Burk plot analysis indicated that curcumin is a non-competitive inhibitor of PhK with a Ki of 0.075 mM. Overall, our results indicate that curcumin is a potent and selective inhibitor of phosphorylase kinase, a key regulatory enzyme involved in the metabolism of glycogen. This has important implications for the anti-proliferative effects of curcumin.

Binding, Competitive↗

PubMed1988

Curcumins as inhibitors of nitrosation in vitro.

The effects of turmeric extract and its pure yellow pigments curcumin I, II and III were tested on the nitrosation of methylurea by sodium nitrite at pH 3.6 and 30 degrees C. The nitrosomethylurea formed was monitored by checking the mutagenicity in S. typhimurium strains TA1535 and TA100 without metabolic activation. Turmeric extract as well as curcumins exhibit dose-dependent decreases of nitrosation. Curcumin III was the most effective nitrosation inhibitor among the compounds tested. The simultaneous treatment of inhibitor with nitrosation precursors was essential and pre- or post-treatment of inhibitor had no effect on the mutagenicity of nitrosomethylurea. The binding of nitrite with the inhibitors was studied at pH 3.6 and 30 degrees C. Curcumin I shows a dose-dependent depletion of nitrite ions thus making nitrite non-available for nitrosation. Curcumin I and III when tested also showed a time-dependent depletion of nitrite ions at pH 3.6 and 30 degrees C. Curcumin III has a higher affinity for nitrite ions than curcumin I.

Catechols↗

PubMed1994

Curcumin inhibits TPA induced expression of c-fos, c-jun and c-myc proto-oncogenes messenger RNAs in mouse skin.

Curcumin is a major chemical constituent of turmeric normally eaten by humans. 12-O-Tetradecanoyl phorbol-13-acetate (TPA) is a strong promoter of chemically induced skin cancer. The exact mechanism by which TPA promotes skin cancer is not clear. However, it is known that TPA elevates the expression of oncogenes involved in cell proliferation. Recently, it has been shown that turmeric or curcumin significantly inhibits TPA-induced tumor promotion on mouse skin. However, the mechanism by which curcumin inhibits TPA-induced tumor promotion is not known. In the present studies, we investigated the effect of curcumin on the expression of c-fos, c-jun and c-myc oncogenes in TPA-treated mouse skin in CD-1 mice. A 30-nmol dose of TPA increased the levels of mRNAs for c-fos, c-jun and c-myc oncogenes by 2-3-fold compared with control. Topical application on the dorsal side of the skin with 1 mumol, 10 mumol, 20 mumol or 30 mumol of curcumin 30 min before TPA treatment inhibited the TPA-induced expression of these proto-oncogenes. Inhibition of expression of c-fos and c-jun was more pronounced than that of c-myc. A dose of 10 mumol of curcumin was found to inhibit 90% TPA-induced expression of c-fos and c-jun, and 60% of c-myc. These data strongly suggest that curcumin may inhibit skin cancer through the modulation of expression of these proto-oncogenes.

Animals↗

PubMed2006

Induction of early apoptosis and ROS-generation activity in human gingival fibroblasts (HGF) and human submandibular gland carcinoma (HSG) cells treated with curcumin.

OBJECTIVE: Curcumin [1] is well known to possess apoptosis-inducing activity in some cancer cells, but little is known about its activity in normal cells of oral origin, such as HGF. The aim of the present study was to clarify the relationship between early apoptosis in HGF and the induction of reactive oxygen species (ROS) generation by curcumin. DESIGN: We treated HGF and HSG cells with curcumin [1] and the related compounds biseugenol [2], eugenol [3], alpha-diisoeugenol [4], and isoeugenol [5] and measured cell survival (MTT method), ROS generation (DCFH-DA staining), and induction of early apoptosis. Early apoptosis was detected by monitoring loss of mitochondrial membrane potential (DeltaPsi(m)) by JC-1 staining and externalization of phosphatidylserine (PS) on the cell surface by annexin V-FITC/PI staining combined with flow cytometry. RESULTS: The cytotoxic activities of curcumin [1] and [4] were similar and were nearly 10- to 100-fold stronger than those of the other compounds. Only curcumin was able to induce ROS generation and early apoptosis. Loss of DeltaPsi(m), PS externalization and ROS generation were significantly more pronounced in HGF cells than in HSG cells at curcumin concentrations lower than about 15microM, and were inhibited by the addition of the antioxidants N-acetyl-l-cysteine and glutathione. CONCLUSION: The potent PS externalization and loss of DeltaPsi(m) in curcumin-treated HGF cells appears to be mediated by ROS generation.

Antineoplastic Agents↗