While most types of malignancies remain recalcitrant to treatment, application of natural products or their analogs in daily life has offered some hopes as an effective prophylaxis against cancer onset and progression in the past decades. Emerging evidence supports a link between garlic consumption and decreased cancer incidence. Notably, aged garlic extract (AGE) exhibits stronger anti-cancer activities than that of fresh garlic, by virtue of enrichment of several AGE-specific organosulfur compounds, including S-allylmercaptocysteine (SAMC). In this review, we summarize the up-to-date mechanistic pathways associated with the anti-proliferative, anti-metastatic and pro-apoptotic effects of SAMC in various cancer models. Based upon the proven safety and improved understanding on its anti-neoplastic properties, SAMC has gained recognition as a promising daily food supplement for cancer prevention or management.
Animals ; Antineoplastic Agents, Phytogenic ; chemistry ; pharmacology ; therapeutic use ; Apoptosis ; drug effects ; Cysteine ; analogs & derivatives ; chemistry ; pharmacology ; therapeutic use ; Disease Models, Animal ; Garlic ; chemistry ; Humans ; Molecular Structure ; Neoplasms ; drug therapy ; metabolism ; Signal Transduction ; drug effects

Bucillamine is used for the treatment of rheumatoid arthritis. This study investigated the protective effects of bucillamine against cisplatin-induced damage in auditory cells, the organ of Corti from postnatal rats (P2) and adult Balb/C mice. Cisplatin increases the catalytic activity of caspase-3 and caspase-8 proteases and the production of free radicals, which were significantly suppressed by pretreatment with bucillamine. Bucillamine induces the intranuclear translocation of Nrf2 and thereby increases the expression of gamma-glutamylcysteine synthetase (gamma-GCS) and glutathione synthetase (GSS), which further induces intracellular antioxidant glutathione (GSH), heme oxygenase 1 (HO-1) and superoxide dismutase 2 (SOD2). However, knockdown studies of HO-1 and SOD2 suggest that the protective effect of bucillamine against cisplatin is independent of the enzymatic activity of HO-1 and SOD. Furthermore, pretreatment with bucillamine protects sensory hair cells on organ of Corti explants from cisplatin-induced cytotoxicity concomitantly with inhibition of caspase-3 activation. The auditory-brainstem-evoked response of cisplatin-injected mice shows marked increases in hearing threshold shifts, which was markedly suppressed by pretreatment with bucillamine in vivo. Taken together, bucillamine protects sensory hair cells from cisplatin through a scavenging effect on itself, as well as the induction of intracellular GSH.
Animals ; Antioxidants/*metabolism/*pharmacology ; Apoptosis/drug effects ; Caspase 3/metabolism ; Caspase 8/metabolism ; Cell Line ; Cisplatin/*toxicity ; Cysteine/*analogs & derivatives/pharmacology ; Gene Expression Regulation/*drug effects ; Gene Knockdown Techniques ; Glutathione/*metabolism ; Heme Oxygenase-1/genetics ; Intracellular Space/metabolism ; Male ; Metabolic Detoxication, Phase II/genetics ; Mice ; NF-E2-Related Factor 2/genetics ; Nitric Oxide/biosynthesis ; Organ of Corti/*drug effects/*metabolism ; RNA Interference ; Rats ; Reactive Oxygen Species/metabolism ; Superoxide Dismutase/genetics

OBJECTIVEThe aim of this study was to explore the effect of SPARC on the anti-cancer effect of gemcitabine and underlying mechanism in pancreatic cancer.

METHODSAfter treating with gemcitabine, the proliferation rate of MIA PaCa2, MIA PaCa2/V and MIA PaCa2/SPARC69 cells was detected by MTT assay. The cell cycle distribution and cell apoptosis in each group were examined by flow cytometry, and the capability of clone formation was tested by adhesion-dependent clone formation assay. The apoptosis-related proteins were analyzed by Western blot.

RESULTSThe growth of pancreatic cancer cells was inhibited by gemcitabine in a time-dependent and dose-dependent manner. Its IC50 at 24, 48, and 72-h was (40.1 ± 2.5) µmol/L, (15.0 ± 0.5) µmol/L and (6.6 ± 0.1) µmol/L, respectively. The overexpression of SPARC increased the inhibitory effect of gemcitabine on growth of pancreatic cancer MIA PaCa2/SPARC69 cells, presenting a dose- and time- dependent manner. Its IC50 at 24, 48, 72 h was (24.3 ± 1.5) µmol/L, (7.7 ± 0.3) µmol/L and (4.8 ± 0.2) µmol/L, respectively. The clone formation assay showed that before gemcitabine treatment, the clone numbers of MIA PaCa2, MIA PaCa2/V and MIA PaCa2/SPARC69 cells were (2350 ± 125), (2130 ± 120) and (1567 ± 11), respectively. After gemcitabine treatment, the clone numbers of MIA PaCa2, MIA PaCa2/V and MIA PaCa2/SPARC69 cells were ( 1674 ± 79) , (1587 ± 94) and (557 ± 61), respectively. The overexpression of SPARC enhanced the chemosensitivity of MIA PaCa2 cells to gemcitabine chemotherapy. After treating with 10 µmol/L gemcitabine for 48 h, the ratio of G0/G1 cells in MIA PaCa2, MIA PaCa2/V and MIA PaCa2/SPARC69 cells were (56.0 ± 5.5)%, (55.0 ± 4.5)% and (68.0 ± 7.0)%, respectively. The cells arrested at G0/G1 phase were significantly increased in the MIA PaCa2/SPARC69 cells. The apoptosis rates of MIA PaCa2, MIA PaCa2/V and MIA PaCa2/SPARC69 cells were (22.4 ± 2.5)%, (19.9 ± 2.0)% and (37.7 ± 3.9)%, respectively, indicating that overexpression of SPARC enhanced the gemcitabine-induced apoptosis in MIA PaCa2 cells. The Western blot analysis showed that, compared with MIA PaCa2 and MIA PaCa2/V cells, the expression of caspase-2, -8, -9 and cleaved PARP protein was significantly increased, while the expression of Bcl-2 was not changed significantly in the MIA PaCa2/SPARC69 cells.

CONCLUSIONSPARC can enhance the chemosensitivity of pancreatic cancer cells to gemcitabine via regulating the expression of apoptosis-related proteins.

Antimetabolites, Antineoplastic ; administration & dosage ; pharmacology ; Apoptosis ; drug effects ; Caspase 2 ; metabolism ; Caspase 8 ; metabolism ; Caspase 9 ; metabolism ; Cell Cycle ; drug effects ; Cell Cycle Checkpoints ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cysteine Endopeptidases ; metabolism ; Deoxycytidine ; administration & dosage ; analogs & derivatives ; pharmacology ; Dose-Response Relationship, Drug ; Drug Resistance, Neoplasm ; Humans ; Osteonectin ; metabolism ; Pancreatic Neoplasms ; metabolism ; pathology ; Poly(ADP-ribose) Polymerases ; metabolism ; Time Factors

The apparatus for intrinsic dissolution test recorded in United States Pharmacopeia (USP) integrating with fiber-optic drug dissolution test system (FODT) were used to real-time monitor intrinsic dissolution processes of alliin in four media which were water, solution of HCl with pH 1.2, buffer solution of acetate with pH 4.5, and buffer solution of phosphate with pH 6.8. The intrinsic dissolution rate (IDR) and the similarity factor (f2) of two intrinsic dissolution curves with two apparatuses were calculated. The IDR values of alliin with rotating disk system were 28.1.3, 33.55, 28.38 and 30.95 mg x cm(-2) x min(-1) in four media, respectively. And the IDR values of alliin with stationary disk system were 44.16, 47.07, 45.11 and 51.34 mg x cm(-2) x min(-1), respectively. The similarity factors were 56.42, 50.75, 40.30 and 40.64, respectively. The results showed that the intrinsic alliin dissolution rates were much greater than 1 mg x cm(-2) x min(-1). It inferred that alliin dissolution would not be the rate limiting step to absorption.
Cysteine ; analogs & derivatives ; chemistry ; Fiber Optic Technology ; Solubility

The aimed of this study was to prepare stabilized thiomers to overcome the poor stability character of traditional thiomers. Poly(acrylic acid)-cysteine (PAA-Cys) was synthesized by conjugating cysteine with poly(acrylic acid) and poly(acrylic acid)-cysteine-6-mercaptonicotinic acid (PAA-Cys-6MNA, stabilized thiomers) was synthesized by grafting a protecting group 6-mercaptonicotinic acid (6MNA) with PAA-Cys. The free thiol of PAA-Cys was determined by Ellmann's reagent method and the ratio of 6MNA coupled was determined by glutathione reduction method. The study of permeation enhancement and stabilized function was conducted by using Franz diffusion cell method, with fluorescein isothiocyanate dextran (FD4) used as model drug. The influence of polymers on tight junctions of Caco-2 cell monolayer was detected with laser scanning confocal fluorescence microscope. The results indicated that both PAA-Cys and PAA-Cys-6MNA could promote the permeation of FD4 across excised rat intestine, and the permeation function of PAA-Cys-6MNA was not influence by the pH of the storage environment and the oxidation of air after the protecting group 6MNA was grafted. The distribution of tight junction protein of Caco-2 cell monolayer F-actin was influenced after incubation with PAA-Cys and PAA-Cys-6MNA. In conclusion, stabilized thiomers (PAA-Cys-6MNA) maintained the permeation function compared with the traditional thiomers (PAA-Cys) and its stability was improved. The mechanism of the permeation enhancement function of the polymers might be related to their influence on tight junction relating proteins of cells.
Acrylic Resins ; chemistry ; Actins ; metabolism ; Animals ; Caco-2 Cells ; Cysteine ; chemistry ; Dextrans ; Fluorescein-5-isothiocyanate ; analogs & derivatives ; Glutathione ; Humans ; Intestinal Absorption ; Intestinal Mucosa ; drug effects ; Nicotinic Acids ; chemistry ; Rats ; Sulfhydryl Compounds ; chemistry

OBJECTIVETo compare the efficacy and safety of Stronger Neo-Minophagen C (SNMC) in the treatment of chronic hepatitis B.

METHODSWe searched MEDLINE, EMBASE, CBM, and CNKI up to December, 2012 to identify randomized controlled trials (RCTs) comparing Stronger Neo-Minophagen C plus other therapy versus others therapy for chronic hepatitis B. Two reviewers independently assessed the risk of bias and extracted data from the included RCTs according to the Cochrane Reviewers Handbook 5.1.0. Meta-analyses were performed using RevMan 5.1 software.

RESULTSThirty-one trials involving 2753 patients were included in the analysis. The results of meta-analyses showed that SNMC improved hepatic functions of the patients by reducing ALT (MD=-31.63, 95% CI: -51.57, -11.70), AST (MD=-18.70, 95% CI:-25.10, -12.30), TBIL (MD=-12.17, 95% CI: -17.63,-6.71), HA (MD=-94.89, 95% CI: -125.19, -64.60), LN (MD=-40.08, 95% CI: -52.38,-27.78), IV-C (MD=-50.61, 95% CI:-63.40, -37.81), PC-III (MD=-49.71, 95% CI: -71.72, -27.69) as compared with the control group. The seroconversion rate of HBeAg (OR=2.23, 95% CI: 1.70, 2.94), HBV-DNA (OR=2.20, 95% CI: 1.70, 2.84), HBsAg (OR=2.25, 95% CI: 1.24 , 4.07), total response rate (OR=4.37, 95% CI: 2.62, 7.28), and ALT normalization rate (OR=3.77, 95% CI: 2.46, 5.79) were all significantly higher in the combined therapy group than in the control group.

CONCLUSIONSNMC plus other therapy is more effective than other therapy alone in improving the hepatic function and hepatic fibrosis and increasing hepatic seroconversion rate in patients with chronic hepatitis B without causing serious adverse events. But considering the low quality of the included studies, the results should be interpreted with caution and awaits further confirmation by high-quality, large-scale RCTs.

Cysteine ; therapeutic use ; Drug Combinations ; Glycine ; therapeutic use ; Glycyrrhetinic Acid ; analogs & derivatives ; therapeutic use ; Hepatitis B Surface Antigens ; blood ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; drug therapy ; Humans ; Liver Cirrhosis ; drug therapy ; Randomized Controlled Trials as Topic

In our previous work, we found that trivalent dimethylarsinous acid (DMA(III)) have high affinity binding to cysteine residue 13 of rat hemoglobin. However, it is still unknown why arsenic intermediate metabolite DMA(III) has high binding affinity for Cysl3 but not for other cysteine residues 93, 140, 111 and 125. In order to better understand the molecular mechanism of DMA(III) with rat hemoglobin, we have done current study. So, SD rats were divided into control and arsenic-treated groups randomly. Arsenic species in lysate of red blood cells were analyzed by HPLC-ICP-MS, and then determined by a hybrid quadrupole TOF MS. In addition, trivalent DMA(III) binds to different cysteine residues in rat hemoglobin alpha and beta chains were also simulated by Molecular Docking. Only Cys13 in alpha chain is able to bind to DMA(III) from the experiment results. Cys13 of alpha chain in rat hemoglobin is a specific binding site for DMA(III), and we found that amino acids compose pockets structure and surround Cys13 (but not other cysteine residues), make DMA(III) much easy to bind cysteine 13. Taken together, the DMA(III) specific binding to Cys13 is related to spatial structure of Cys13.
Animals ; Arsenic ; metabolism ; Binding Sites ; Cacodylic Acid ; analogs & derivatives ; chemistry ; Chromatography, High Pressure Liquid ; Cysteine ; metabolism ; Hemoglobins ; metabolism ; Mass Spectrometry ; Peptide Fragments ; metabolism ; Rats

OBJECTIVETo evaluate the effect of decoction of turtle shell for anti-fibrosis combined with stronger neo-minophagen C on the indices of hepatic fibrosis in chronic hepatitis B.

METHODThe 94 cases of chronic viral hepatitis B patients were randomly divided into two groups. The treatment group was treated with stronger neo-minophagen C 100 mL dissolved in 10% dextrose 250 ml once a day intravenously, combined with decoction of turtle shell for anti-fibrosis one powder daily. And the control group was treated with stronger neo-minophagen C alone, 3 months as a course. Liver fibrosis indexes and liver function index were tested for two groups of patients before and after the treatment.

RESULTBoth the difference of liver fibrosis indexes between the treatment group and the control group and before and after the treatment in the treatment group had statistical significance (P < 0.01). Both the difference of liver function index between the treatment group and the control group and before and after the treatment in the treatment group had statistical significance (P < 0.01). The basic cure rate and total effective rate were 40% and 84.0% in the treatment group and 27.27% and 86.18% in the control group respectively with significant difference. The treatment group was superior to control group in the mean size of diameter of portal vein and the thickness of spleen (P < 0.01).

CONCLUSIONDecoction of turtle shell for anti-fibrosis combined with stronger neo-minophagen C could significantly improve the clinical efficacy and the liver fibrosis indexes and liver function index in chronic hepatitis B.

Adult ; Aged ; Alanine Transaminase ; blood ; Animal Shells ; chemistry ; Animals ; Aspartate Aminotransferases ; blood ; Cysteine ; administration & dosage ; therapeutic use ; Drug Combinations ; Drug Therapy, Combination ; Female ; Glycine ; administration & dosage ; therapeutic use ; Glycyrrhetinic Acid ; administration & dosage ; analogs & derivatives ; therapeutic use ; Hepatitis B, Chronic ; complications ; Humans ; Liver Cirrhosis ; blood ; drug therapy ; etiology ; Male ; Medicine, Chinese Traditional ; methods ; Middle Aged ; Tissue Extracts ; therapeutic use ; Treatment Outcome ; Turtles ; gamma-Glutamyltransferase ; blood

Aeroto-Niu-O16, an oxygen-tolerant bovine rumen bacterium, is capable of aerobically reducing isoflavones daidzein and genistein to dihydrodaidzein and dihydrogenistein through catalytic hydrogenation. In this study, it was found that bacterium strain Aeroto-Niu-O16 was able to cleavage the C-ring of liquiritigenin (LG), which is one of the main biologically active components of licorice roots, in the presence of atmospheric oxygen. LG was prepared by acid hydrolysis of the crude extract of licorice roots. The metabolite of LG obtained in strain Aeroto-Niu-O16 was identified as davidigenin (DG) based on the data of UV, MS, 1H and 13C NMR. The maximal concentration of LG that the strain Aeroto-Niu-O16 was able to transform effectively was 0.8 mmol x L(-1) and the average productivity of the metabolite DG was 71.7%. Furthermore, when 0.1% (m/v) of L-cysteine or sodium thiosulfate was added in the cultural medium, the average bioconversion rate of LG was increased from 71.7% to 78.3% and 77.2%, respectively. The in vitro antioxidant investigation showed that 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity of DG was significantly or extremely significantly higher than that of LG at the concentrations from 0.2 mmol x L(-1) to 1.6 mmol x L(-1). We discoverd for the first time that LG can be converted to DG, which has stronger and wider biological activities, through microbial biotransformation method.
Animals ; Antioxidants ; isolation & purification ; metabolism ; pharmacology ; Bacteria, Anaerobic ; isolation & purification ; metabolism ; Biotransformation ; Biphenyl Compounds ; metabolism ; Cattle ; Chalcone ; analogs & derivatives ; metabolism ; pharmacology ; Cysteine ; pharmacology ; Flavanones ; isolation & purification ; metabolism ; pharmacology ; Glycyrrhiza ; chemistry ; Picrates ; metabolism ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry ; Rumen ; microbiology ; Thiosulfates ; pharmacology

OBJECTIVETo investigate the effect of S-allyl-L-cysteine (SAC) on isolated rat heart subject to ischemia/reperfusion(I/R) injury and the mechanisms.

METHODSThe isolated perfused rat hearts on a Langendorff apparatus were subjected to global ischemia for 30 min and followed by 120 min of reperfusion. Hemodynamic index, the production of formazan and the level of lactate dehydrogenase (LDH) in the coronary effluent were determined. Superoxide dismutase (SOD) and reactive oxygen species (ROS) in myocardial homogenates were measured.

RESULTSCompared with I/R group, the hemodynamics were greatly improved, the production of formazan was increased, and LDH level in effluent was reduced in SAC group. SAC improved the SOD activity and significantly decreased the level of ROS. In addition, threonine (Thr) attenuated the protective effect of SAC significantly.

CONCLUSIONSAC has protective effect against myocardial ischemia/reperfusion injury on rats. The possible mechanism is that SAC be transported into the cell through alanine-serine-cysteine-transporter 1 (ASCT-1) improves SOD activity and reduces the level of ROS.

Animals ; Cysteine ; analogs & derivatives ; pharmacology ; In Vitro Techniques ; Male ; Myocardial Ischemia ; physiopathology ; Myocardial Reperfusion Injury ; physiopathology ; prevention & control ; Protective Agents ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species ; metabolism ; Superoxide Dismutase ; metabolism