curcumin and allyl-sulfide

Multidrug resistance is a principal mechanism by which tumors become resistant to structurally and functionally unrelated anticancer drugs. Resistance to chemotherapy has been correlated with overexpression of p-glycoprotein (p-gp), a member of the ATP-binding cassette (ABC) superfamily of membrane transporters. P-gp mediates resistance to a broad-spectrum of anticancer drugs including doxorubicin, taxol, and vinca alkaloids by actively expelling the drugs from cells. Use of specific inhibitors/blocker of p-gp in combination with clinically important anticancer drugs has emerged as a new paradigm for overcoming multidrug resistance. The aim of this paper is to review p-gp regulation by dietary nutraceuticals and to correlate this dietary nutraceutical induced-modulation of p-gp with activity of anticancer drugs.

Topics: Abietanes; Alkaloids; Allyl Compounds; Animals; Antineoplastic Agents; ATP Binding Cassette Transporter, Subfamily B; Benzodioxoles; beta Carotene; Biflavonoids; Capsaicin; Catechin; Catechols; Curcumin; Dietary Supplements; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Drug Synergism; Fatty Alcohols; Furocoumarins; Humans; Indoles; Limonins; Neoplasms; Phytotherapy; Piperidines; Polyunsaturated Alkamides; Proanthocyanidins; Quercetin; Resveratrol; Stilbenes; Sulfides; Tea; Triterpenes; Xanthophylls

Topics: Administration, Oral; Administration, Topical; Allyl Compounds; Animals; Anticarcinogenic Agents; Antioxidants; Carcinogens; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Cocarcinogenesis; Curcumin; Female; Flavonoids; Humans; Male; Mice; Mice, Inbred SENCAR; Neoplasms, Radiation-Induced; Papilloma; Phenols; Phytotherapy; Plants, Medicinal; Polymers; Reactive Oxygen Species; Resveratrol; Silymarin; Skin Neoplasms; Stilbenes; Sulfides; Tea; Ultraviolet Rays; Zingiber officinale

Reactivation of tumour suppressor genes that have been silenced by promoter methylation is a very attractive molecular target for cancer therapy. The treatment of a squamous cervical cancer cell line, SiHa, with 20 μM curcumin and genistein resulted in demethylation of promoter of the RARβ2 gene and led to the reactivation of the gene. The degree of methylation as observed by MSP decreased as the time period of treatment was increased from 72 h to 6 days. In HeLa cells (an adenocarcinoma cervical cancer cell line) there was also reversal of hypermethylation of the RARβ2 gene after six days of treatment with 20 μM curcumin. However, allyl sulphide treatment (20 μM) did not cause the reversal of hypermethylation until 72 h of treatment in the SiHa cell line. This is the first report to show the reversal of hypermethylation of the RARβ2 gene by genistein and curcumin in cervical cancer cell lines. Furthermore, these compounds acted as doublepronged agents as they caused apoptosis in the treated cervical cancer cell lines in addition to reversal of promoter hypermethylation.

Topics: Allyl Compounds; Antineoplastic Agents; Biological Products; Cell Line, Tumor; Curcumin; DNA Methylation; Female; Genistein; Humans; Receptors, Retinoic Acid; Sulfides; Uterine Cervical Neoplasms

Spice active principles are reported to have anti-diabetic, anti-hypercholesterolemic, antilithogenic, anti-inflammatory, anti-microbial and anti-cancer properties. In our previous report we have shown that spices and their active principles inhibit 5-lipoxygenase and also formation of leukotriene C4. In this study, we report the modulatory effect of spice active principles viz., eugenol, capsaicin, piperine, quercetin, curcumin, cinnamaldehyde and allyl sulphide on in vitro human platelet aggregation. We have demonstrated that spice active principles inhibit platelet aggregation induced by different agonists, namely ADP (50microM), collagen (500microg/ml), arachidonic acid (AA) (1.0mM) and calcium ionophore A-23187 (20microM). Spice active principles showed preferential inhibition of arachidonic acid-induced platelet aggregation compared to other agonists. Among the spice active principles tested, eugenol and capsaicin are found to be most potent inhibitors of AA-induced platelet aggregation with IC50 values of 0.5 and 14.6microM, respectively. The order of potency of spice principles in inhibiting AA-induced platelet aggregation is eugenol>capsaicin>curcumin>cinnamaldehyde>piperine>allyl sulphide>quercetin. Eugenol is found to be 29-fold more potent than aspirin in inhibiting AA-induced human platelet aggregation. Eugenol and capsaicin inhibited thromboxane B2 (TXB2) formation in platelets in a dose-dependent manner challenged with AA apparently by the inhibition of the cyclooxygenase (COX-1). Eugenol-mediated inhibition of platelet aggregation is further confirmed by dose-dependent decrease in malondialdehyde (MDA) in platelets. Further, eugenol and capsaicin inhibited platelet aggregation induced by agonists-collagen, ADP and calcium ionophore but to a lesser degree compared to AA. These results clearly suggest that spice principles have beneficial effects in modulating human platelet aggregation.

Topics: Acrolein; Adenosine Diphosphate; Alkaloids; Allyl Compounds; Arachidonic Acid; Benzodioxoles; Calcimycin; Capsaicin; Collagen Type III; Curcumin; Eugenol; Humans; Malondialdehyde; Piperidines; Platelet Aggregation; Platelet Aggregation Inhibitors; Polyunsaturated Alkamides; Quercetin; Spices; Sulfides; Thromboxanes

Since flavonoids and other natural compounds exert beneficial effects on human health, their consumption rapidly increases. However, they can modulate the activity of xenobiotic-metabolizing enzymes involved in activation and detoxification of food and environmental carcinogens. Thus, their potential negative effects should be examined.. The induction effects of selected chemopreventive compounds, administered per orally by gastric gavages to rats, on cytochrome P450 (CYP) 1A and 2B were determined in liver and small intestine using Western blotting analysis and specific metabolic activity assays.. Comparing CYPs expression along small intestine, the highest induction was observed in the proximal part near pylorus with rapid decrease towards the distal part. In response to chemopreventive compounds, the marked induction of CYP1A and CYP2B in liver was observed after diallyl sulphide and flavone treatment. In small intestine, beta-naphthoflavone, diallyl sulphide and curcumin induced CYP1A1 and CYP2B1. In both tissues, resveratrol did not significantly affect CYPs expression. The results of Western blotting detection of CYPs correlate well with their specific enzymatic activities.. Presented data indicate ambiguous impact of chemopreventive compounds on cytochromes P450, main xenobiotic-metabolizing enzymes. Thus, the question of safety and unlimited consumption of these compounds arises.

Topics: Allyl Compounds; Animals; Anticarcinogenic Agents; beta-Naphthoflavone; Blotting, Western; Curcumin; Cytochrome P-450 CYP1A1; Cytochrome P-450 CYP2B1; Cytochrome P-450 Enzyme System; Flavonoids; Intestine, Small; Liver; Male; Rats; Rats, Wistar; Resveratrol; Stilbenes; Sulfides; Xenobiotics

The human diet contains a variety of compounds that exhibit chemopreventive effects towards an array of xenobiotics. In the present study, the antigenotoxic potential of selected dietary constituents including Diallyl sulfide (DAS), Indole-3-carbinol (I3C), Curcumin (CUR), and Black tea polyphenols (BTP) has been evaluated in the Salmonella typhimurium reverse mutation and mammalian in vivo cytogenetic assays. In addition, the anticlastogenic effect of the above dietary constituents was identified towards Benzo(a)pyrene (BaP) and cyclophosphamide- (CP) induced cytogenetic damage in mouse bone marrow cells. The induction of BaP and CP induced chromosomal aberrations, micronuclei formation, and sister chromatid exchanges (SCEs) were found to be inhibited in a dose-dependent manner by DAS, I3C, CUR, and BTP. Thus the study reveals the antimutagenic potential of these dietary compounds towards BaP- and CP-induced genotoxicity in microbial and mammalian test systems.

Topics: Allyl Compounds; Animals; Antimutagenic Agents; Benzo(a)pyrene; Bone Marrow Cells; Chromosome Aberrations; Curcumin; Cyclophosphamide; Diet; Dose-Response Relationship, Drug; Flavonoids; Indoles; Male; Mice; Micronuclei, Chromosome-Defective; Mutagenicity Tests; Phenols; Polymers; Salmonella typhimurium; Sister Chromatid Exchange; Sulfides; Tea

Spice components and their active principles are potential antioxidants. In this study we examined the effect of phenolic and non-phenolic active principles of common spices on copper ion-induced lipid peroxidation of human low density lipoprotein (LDL) by measuring the formation of thiobarbituric acid reactive substance (TBARS) and relative electrophoretic mobility (REM) of LDL on agarose gel. Curcumin, capsaicin, quercetin, piperine, eugenol and allyl sulfide inhibited the formation of TBARS effectively through out the incubation period of 12 h and decreased the REM of LDL. Spice phenolic active principles viz. curcumin, quercetin and capsaicin at 10 microM produced 40-85% inhibition of LDL oxidation at different time intervals while non-phenolic antioxidant allyl sulfide was less potent in inhibiting oxidation of LDL. However, allyl sulfide, eugenol and ascorbic acid showed pro-oxidant activity at lower concentrations (10 microM) and antioxidant activity at higher concentrations (50 microM) only. Among the spice principles tested quercetin and curcumin showed the highest inhibitory activity while piperine showed least antioxidant activity at equimolar concentration during initiation phase of oxidation of LDL. The inhibitory effect of curcumin, quercetin and capsaicin was comparable to that of BHA, but relatively more potent than ascorbic acid. Further, the effect of curcumin, quercetin, capsaicin and BHA on initiation and propagation phases of LDL oxidation showed that curcumin significantly inhibited both initiation and propagation phases of LDL oxidation, while quercetin was found to be ineffective at propagation phase. These data suggest that the above spice active principles, which constitute about 1-4% of above spices, are effective antioxidants and offer protection against oxidation of human LDL.

Topics: Alkaloids; Allyl Compounds; Ascorbic Acid; Benzodioxoles; Butylated Hydroxyanisole; Capsaicin; Curcumin; Eugenol; Humans; In Vitro Techniques; Lipoproteins, LDL; Oxidation-Reduction; Piperidines; Polyunsaturated Alkamides; Quercetin; Spices; Sulfides