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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Licorice has been used as medicine and as sweetening agent in food products. The major water-soluble constituent of licorice is glycyrrhizin (GL), an oleanane triterpenoide, which is known to be partly hydrolyzed by glucuronidase to its aglycone glycyrrhetinic acid (GA) which exists in 18 alpha (alpha-GA) and 18 beta (beta-GA) stereoisomeric forms. In this study alpha-GA and beta-GA were found to inhibit the mutagenicity of benzo[a]pyrene (B[a]P), 2-aminofluorene and aflatoxin B1 in Salmonella typhimurium TA98 and TA100. beta-GA was more effective than alpha-GA as an antimutagen. In the two-stage skin tumorigenesis protocol using 7,12-dimethylbenz[a]anthracene (DMBA) as the tumor initiating agent followed by twice weekly applications of 12-O-tetradecanoylphorbol-13-acetate as tumor promoter, pretreatment of SENCAR mice with alpha-GA or beta-GA resulted in significant protection against tumor initiation as well as tumor promotion. As an anti-tumor initiating agent, beta-GA was found to be more effective than alpha-GA. Similarly, topical application of beta-GA was found to be more effective than alpha-GA in inhibiting the binding of both [3H]B[a]P and [3H]DMBA to epidermal DNA. However, as an anti-tumor promoter, alpha-GA and beta-GA showed comparable effects. Our results suggest that both alpha-GA and beta-GA possess substantial anti-skin tumor initiating and anti-skin tumor promoting activities.
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PMID:Inhibition of mutagenicity in Salmonella typhimurium and skin tumor initiating and tumor promoting activities in SENCAR mice by glycyrrhetinic acid: comparison of 18 alpha- and 18 beta-stereoisomers. 189 8

Licorice (Glycyrrhiza glabra), a Mediterranean plant, has been used as an antidote, demulcent, and elixir folk medicine for generations in China. The main water-soluble constituent of licorice is glycyrrhizin (GL), which has been shown to possess several pharmacological properties. In this study, we show that oral feeding of GL to Sencar mice resulted in substantial protection against skin tumorigenesis caused by 7,12-dimethyl-benz [a]anthracene (DMBA) initiation and 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion. The latent period prior to the onset of tumor development was considerably prolonged in GL-fed animals compared with animals not fed GL and resulted in significant decrease in the number of tumors per mouse, during and at the termination of the experiment. Oral feeding of GL in drinking water also resulted in inhibition in the binding of topically applied [3H]benzo[a]pyrene and [3H]DMBA to epidermal DNA. The possible mechanism(s) of the antitumor-initiating activity may be due to the involvement of GL as inhibitor of the carcinogen metabolism followed by DNA adduct formation. Our results suggest that GL possesses considerable antitumorigenic activity and could prove useful in protecting some forms of human cancer.
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PMID:Inhibition of mouse skin tumor-initiating activity of DMBA by chronic oral feeding of glycyrrhizin in drinking water. 190 33

The immunopotentiating effects of the traditional Chinese drugs Ginsenoside (GS) and Glycyrrhiza polysaccharide (GPS) are reported. It was demonstrated that GS promotes the phagocytic activity of plaque-forming cells (PFC) and enhances the mitogenesis of T and B lymphocytes primed by mitogens. The mechanism of these effects is related to the ratio of cGMP to cAMP. GS also plays a role in the NKC-IFN-IL-2 regulatory system, inhibits the growth of tumor cells, and antagonizes the suppression of ADCC and NK cytotoxicities in mice with surgical stress. GS exhibits bidirectional effects on immunological functions. GPS increases the phagocytosis of macrophages, induces macrophages to secret IL-1, enhances both NK and ADCC activities, behaves as a mitogen of B lymphocytes, inhibits the multiplication of several viruses, and induces the release of IFN from spleen cells.
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PMID:Immunopotentiating effect of traditional Chinese drugs--ginsenoside and glycyrrhiza polysaccharide. 229 26

In the course of my studies of patients with mineralocorticoid hypertensive disorders, unusual presentations led to unexpected findings, both clinically and in steroid etiologies and regulation. Unique circumstances permitted early studies in defining the autonomy of the aldosterone-producing adenoma. A chance referral brought the index case of 17 alpha-hydroxylase deficiency to the research center. New techniques were developed in unusual ways to measure the metabolites of deoxycorticosterone (DOC) using an anesthetic agent. Procedural delays were followed by the surreptitious transfer of a patient from one hospital to the research center after a benign DOC-secreting tumor had been removed. The delay of DOC and all 17-deoxysteroids to respond normally to ACTH stimulation suggested a possible second regulator of DOC. This observation led to studies that demonstrated divergent responses between DOC and cortisol in diverse conditions. An unexplained mineralocorticoid form of hypertension with suppression of renin and aldosterone, but normal DOC production, is seen in licorice intoxication. After licorice was discontinued we documented the delay in the recovery of the inhibited cortisol metabolism (14 days) and renin-angiotensin system (4 months). Licorice extract given to normal subjects on low sodium diets with and without ACTH suppression showed similar results. Other factors in licorice may thus be operative in terms of renin and aldosterone suppression.
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PMID:My engagement with steroids: a review. 779 16

Enzymes that modulate the level of circulating steroid hormone can be used to combat steroid-dependent disorders. Members of the NADPH-dependent short chain dehydrogenase/reductase (SDR) family control blood pressure, fertility, and natural and neoplastic growth. Despite the fact that only one amino acid residue is strictly conserved in the 60 known members of the family, all appear to have the dinucleotide-binding Rossmann fold and homologous catalytic residues containing the conserved tyrosine. Variation in the amino acid composition of the substrate binding pocket creates specificity of binding for steroids, prostaglandins, sugars and alcohols. Licorice induces high blood pressure by inhibiting an SDR in the kidney, and appears to combat ulcers by inhibiting another in the stomach. Detailed X-ray analyses of various members of the family should allow the design of potent, tissue-specific, highly selective inhibitors.
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PMID:The fascinating complexities of steroid-binding enzymes. 899 82

Members of the NADPH-dependent short chain dehydrogenase/reductase (SDR) family control blood pressure, fertility, and natural and neoplastic growth. Despite the fact that only one amino acid residue is strictly conserved in the 100 known members of the family, all appear to have a dinucleotide-binding Rossmann fold and homologous catalytic residues including the conserved tyrosine. Variation in the binding pocket creates specificity for steroids, prostaglandins, sugars and alcohols. The critically important tyrosine appears to maintain a fixed position relative to the scaffolding of the Rossmann fold and the cofactor position, while the substrate-binding pocket alters in such a way that the dehydrogenation/reduction reaction site is brought into bonding distance of the tyrosine hydroxyl group. Licorice induces high blood pressure by inhibiting an SDR in the kidney. The crystal structure of the complex of 3alpha,20beta-hydroxysteroid dehydrogenase and carbenoxolone reveals the mechanism of enzyme inhibition by licorice. The most potent dehydrogenase enzyme inhibitors are those that displace substrate and cofactor and form strong hydrogen bonds to one or more amino acid residues involved in catalysis.
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PMID:Structure and mechanism of action and inhibition of steroid dehydrogenase enzymes involved in hypertension. 988 33

Licorice root extract and its major isoflavan, glabridin, exhibited varying degrees of estrogen receptor (ER) agonism in different tissues in vitro and in vivo. Animals fed with licorice extract, compared with estradiol and glabridin, showed an increase in creatine kinase (CK) activity, a known marker for estrogen responsive genes, which was higher than expected from the levels of glabridin in the extract. This led us to test for other components that may contribute to this strong estrogen agonist activity. Results indicated that glabrene and isoliquiritigenin, (2',4',4-three hydroxy chalcone) (ILC) in the licorice extract can bind to the human ER with higher affinity (IC50, 1 and 0.5 microM) than glabridin (IC50, 5 microM). The stimulatory effects of glabrene in vivo were tissue specific and similar to those of estradiol. The effect of increasing concentrations of glabrene and ILC on the growth of breast tumor cell were biphasic. Both showed an ER-dependent growth-promoting effect at low concentrations (10 nM-10 microM), and ER-independent antiproliferative activity at concentrations >15 microM. This is the first study to indicate that glabrene, an isoflavene exerted varying degrees of ER agonism in different tissues.
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PMID:Estrogen-like activity of glabrene and other constituents isolated from licorice root. 1159 10

Herbal therapies are commonly used by patients with cancer, despite little understanding about biologically active chemical derivatives. We recently demonstrated that the herbal combination PC-SPES, which contains licorice root, had anti-prostate cancer activity attributable to estrogen(s) that produced a chemical castration. A recent study also demonstrated that licorice root alone decreased circulating testosterone in men. Other studies demonstrated antitumor activity of PC-SPES in vitro associated with decreased expression of the anti-apoptotic protein Bcl-2 and in patients independent of chemical castration, suggesting that other mechanisms of antitumor activity exist separate from chemical castration. In the present study, we assessed licorice root extract for effects on Bcl-2 to identify novel cytotoxic derivatives. Licorice root extract induced Bcl-2 phosphorylation as demonstrated by immunoblot and G2/M cell cycle arrest, similarly to clinically used antimicrotubule agents such as paclitaxel. Bioassay-directed fractionations resulted in a biologically active fraction for Bcl-2 phosphorylation. HPLC separation followed by mass spectrometry and NMR identified 6 compounds. Only one molecule was responsible for Bcl-2 phosphorylation; it was identified as 1-(2,4-dihydroxyphenyl)-3-hydroxy-3-(4'-hydroxyphenyl) 1-propanone (beta-hydroxy-DHP). The effect on Bcl-2 was structure specific, because alpha-hydroxy-DHP, 1-(2,4-dihydroxyphenyl)-2-hydroxy-3-(4'-hydroxyphenyl) 1-propanone, in contrast to beta-hydroxy-DHP, was not capable of Bcl-2 phosphorylation. Pure beta-hydroxy-DHP induced Bcl-2 phosphorylation in breast and prostate tumor cells, G2/M cell cycle arrest, apoptosis demonstrated by Annexin V and TUNEL assay, decreased cell viability demonstrated by a tetrazolium (MTT) assay, and altered microtubule structure. Therefore, these data demonstrate that licorice root contains beta-hydroxy-DHP, which induced Bcl-2 phosphorylation, apoptosis, and G2/M cell cycle arrest, in breast and prostate tumor cells, similarly to the action of more complex (MW >800) antimicrotubule agents used clinically.
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PMID:Novel polyphenol molecule isolated from licorice root (Glycrrhiza glabra) induces apoptosis, G2/M cell cycle arrest, and Bcl-2 phosphorylation in tumor cell lines. 1182 27

Glycyrrhizin, a major component of Glycyrrhiza uralensis (licorice) root, is a saponin and exhibits a number of pharmacological effects, including anti-inflammation, anti-ulcer, anti-allergy, and anticarcinogenesis. Activator protein I (AP-1), a nuclear transcription factor, consists of Jun/Fos heterodimers or Jun/Jun homodimers, and blocking of tumor promoter-induced AP-1 activity could inhibit induced cellular transformation. In order to elucidate the molecular mechanism of glycyrrhizin-induced anticarcinogenesis, effect of glycyrrhizin on the AP-1 activity in untreated and tumor promoter-12-O-tetradecanoylphorbol-13-acetate (TPA)-treated conditions was analyzed in this study. Glycyrrhizin induced the AP-1/TATA reporter activity in a dose-dependent fashion, which was judged by chloramphenicol acetyltransferase assay and electrophoretic mobility-shift assay. Similar results were observed in HepG2 and Vero cells, suggested that glycyrrhizin effect was cell type-independent. In addition, the cis element responsible for glycyrrhizin activity was AP-1 responsive element. Further analysis indicated that glycyrrhizin exhibited a different regulation on the AP-1 activity in untreated and TPA-treated cells. Glycyrrhizin induced the AP-1 activity in untreated cells, while it inhibited the TPA-induced AP-1 activation in TPA-treated cells. These results provide insight into the biological actions of glycyrrhizin and the molecular basis for the development of new chemoprotective agents for cancer.
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PMID:Differential regulation of activator protein 1 activity by glycyrrhizin. 1199 Dec 52

Glycyrrhizic Acid (GL) is the major bioactive triterpene glycoside of licorice root (Glycyrrhiza Radix) extracts possessing a wide range of pharmacological properties (anti-inflammatory, anti-ulcer, anti-allergic, anti-dote, anti-oxidant, anti-tumor, anti-viral etc.). Official sources of GL are Glycyrrhiza glabra L. and Gl. uralensis Fish. (Leguminosae). The content of GL in licorice root is 2-24% of the dry weight. GL is one of the leading natural compounds for clinical trials of chronic active viral hepatitis and HIV infections (preparation Stronger Neo-Minophagen C, SNMC), and its monoammonium salt (glycyram, tussilinar) is used as an anti-inflammatory and anti-allergic remedy. The synthetic transformations of GL on carboxyl and hydroxyl groups were carried out to produce new bioactive derivatives for medicine. GL esters were produced containing fragments of bioactive acids (4-nitrobenzoic, cinnamic, salycilic, acetylsalycilic, nicotinic, isonicotinic). Bioactive amides of GL were synthesized using chloroanhydride technique and N,N'-diciclohexylcarbodiimide (DCC) method. The synthesis of acylthioureids and semicarbazones was carried out via the reaction of triacylisothiocianate of penta-O-acetyl-GL with primary amines and hydrazines. The chain of transformations of trichloranhydride of penta-O-acetyl-GL was made with the introduction of diazoketone groups in the molecule. A new group of GL derivatives to be triterpene glycopeptides was prepared by the activated esters method (N-hydrohysuccinimide-DCC or N-hydroxybenzotriazol-DCC) using alkyl (methyl, ethyl, propyl, butyl, tert-butyl) or benzyl (4-nitrobenzyl) esters of amino acids. The glycyrrhizyl analogs of the known immunostimulator, N-acetyl-muramoyldipeptide (MDP), were synthesized using Reagent Woodward K. A series of ureids and carbamates of GL was synthesized containing 5-amino-5-desoxy-D-xylopyranose units. The synthesis of 4-nitro-4-desoxy-glycosides, modified analogs of GL, was carried out by the oxidative splitting of the carbohydrate part of GL with NaIO(4). Triterpene 2-desoxy-D-glycosides, analogs of GL, were prepared by the glycal method in the presence of iodine-containing promoters or sulfonic acid cation-exchange resin KU-2-8 (H+) and LiBr. New anti-inflammatory and anti-ulcer agents were found among GL derivatives such as esters, amides, ureids, carbamates, thioureids and glycopeptides. GL glycopeptides are of interest as immunomodulators. Some of the chemically modified GL derivatives (salts, amides, glycopeptides) were potent HIV-1 and HIV-2 inhibitors in vitro. Preparation niglizin (penta-O-nicotinate of GL) was studied clinically as an anti-inflammatory agent and is of interest for studies as hepatoprotector and HIV inhibitor.
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PMID:Chemical modification of glycyrrhizic acid as a route to new bioactive compounds for medicine. 1257 Jul 15


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