Concentrations Of Sanguinarine Research Articles

Anti-leishmanial activity of sanguinarine and nano chitosan is modulated by increased ROS production and upregulated TNF-α and iNOS expression

The current study aimed to evaluate the anti-leishmanial activity of sanguinarine and nano chitosan (CS NPs) on Leishmania major, potentially mediated through gene expression of TNF-α and iNOS. To identify the potential targets for sanguinarine, the energy-minimized structure was docked using AutoDock 4.3 software into the active sites of selected peterdin reductase (PTR1) and arginase (ARG-L), which were modeled using homology modeling programs. The colorimetric MTT assay was used to determine the viability of L. major promastigotes subjected to different concentrations of sanguinarine and CS NPs in a concentration- and time-dependent manner. Reactive oxygen species (ROS) levels were measured in treated promastigotes. TNF-α and iNOS expression was determined in PBMCs infected at 24, 48, and 72 h after treatment with sanguinarine and CS NPs. The sanguinarine - PTR1 and ARG-L interactions and calculated energy of these enzymes indicated an excellent affinity for sanguinarine with both enzymes. The IC50 values of the sanguinarine in combination with 10% CS NPs) were 124.76 and 89.25 μM after 24 and 48 h, respectively. Sanguinarine-CS NPs enhanced the expression of TNF-α and iNOs in L. major-infected PBMCs after 24 h (p < 0.05). Sanguinarine-CS NPs could therefore reflect a promising anti-leishmanial agent. Sanguinarine and CS NPs in combination significantly inhibited the proliferation and viability of L.major promastigotes whilst concurrently regulating the expression of TNF-α and iNOS and increasing ROS levels. To better understand the effect of CS NPs and sanguinarine on leishmaniasis, further studies are required in an experimental murine model.

The allelopathic algicides sanguinarine and berberine reduced the dominance of Microcystis in competition with Chlorella

Gramine, sanguinarine and berberine are potential algicides that can significantly inhibit the growth of cyanobacteria. Their effects on other phytoplankton have to be considered, because other phytoplankton species and cyanobacteria usually co-exist. In this study, we have established the relationships between phytoplankton biomasses and their marker pigments. Afterwards, we have assessed the allelopathic effects of three algicides (gramine, sanguinarine and berberine) on the mono-cultured and mixed-cultured cyanobacteria Microcystis and green algae Chlorella. Our results showed that zeaxanthine and lutein can be used to determine the cell densities of Microcystis and Chlorella in the mixed cultures, respectively. Our study also demonstrated that the inhibitory effects of these three allelopathic algicides on the growths of both Microcystis and Chlorella were sanguinarine > gramine > berberine. The concentrations for 50% of the maximal effect (EC50) of sanguinarine against Microcystis and Chlorella were 0.065 and 0.09 mg L−1, respectively; the EC50 values of gramine against Microcystis and Chlorella were 1.687 and 0.870 mg L−1, respectively; and the EC50 values of berberine against Microcystis and Chlorella were 1.969 and 2.397, respectively. The inhibitory effect of allelopathic algicides on the multiple phytoplankton species in mixed cultures was significantly greater than that in monocultures. In mixed cultures without allelopathic addition or in cultures with gramine (0.5–3 mg L−1), the dominant species was Microcystis. However, Chlorella became the dominant species when the concentration of sanguinarine was 0.1 mg L−1 or that of berberine was greater than 0.5 mg L−1. Both species of phytoplankton died completely when sanguinarine levels were greater than 0.1 mg L−1. Our results suggested that the allelopathic algicides sanguinarine and berberine reduced the dominance of Microcystis in competition with Chlorella.

Sanguinarine induces apoptosis in Eimeria tenella sporozoites via the generation of reactive oxygen species

Eimeria tenella (E. tenella) is the most pathogenic genus in Eimeria and can lead to a huge number of deaths of chickens, causing significant economic losses in the poultry industry worldwide. As a natural alkaloid, sanguinarine has many medicinal effects; to a certain extent, it can replace antibiotics and has good application prospects in veterinary medicine. To evaluate the effect of sanguinarine on sporozoites of E.tenella, we used flow cytometry and immunofluorescence staining to detect reactive oxygen species (ROS), mitochondrial membrane potential (MMP), calcium ion (Ca2+), and caspase-3 activation in E.tenella sporozoites treated with different concentrations of sanguinarine. The results of flow cytometry showed that sanguinarine could inhibit the invasion of sporozoites of E.tenella in vitro (P < 0.05) and increase the reactive oxygen species and calcium ions in the sporozoites (P < 0.05). The results of immunofluorescence staining showed that sanguinarine could decrease the mitochondrial membrane potential of sporozoites. Our analysis suggests that sanguinarine can induce apoptosis of E. tenella sporozoites through reactive oxygen species-mediated reduction of the mitochondrial membrane potential and an increase in calcium ion concentration. It follows that sanguinarine is likely to be a novel type of anticoccidiosis drug with good research and clinical application prospects.

Sex differences in the pharmacokinetics and tissue residues of Macleaya cordata extracts in rats

Macleaya cordata extracts (MCE) are listed as feed additives in animal production by the European Food Authority. The core components of MCE are mainly sanguinarine (SA) and chelerythrine (CHE). This study aims to investigate sex differences in the pharmacokinetics and tissue residues of MCE in rats. Male and female rates were intragastrically administered MCE (1.25 mg·kg−1 body weight and 12.5 mg·kg−1 body weight dose for 28 days). SA and CHE concentrations were determined using high-performance liquid chromatography/tandem mass spectrometry. The peak plasma concentration (C max) and area under the curve (AUC) of both CHE and SA were higher in female than in male rats (12.5 mg·kg−1 body weight group), whereas their half-life (T 1/2) and apparent volume of distribution (V d) was lower (p < 0.05). Tissue rfesidue analysis indicated that SA and CHE were more distributed in male than in female rats and were highly distributed in the caecum and liver. SA and CHE were completely eliminated from the liver, kidney, lung, heart, spleen, leg muscle, and caecum after 120 h, indicating they did not accumulate in rats for a long time. Overall, we found that the pharmacokinetics and tissue residues of SA and CHE of male and female rats showed sex differences.

The effects of a myrmecochore-produced chemical on entomopathogenic fungal growth and seed-dispersing ant survival rates and foraging patterns.

Myrmecochory, a type of ant-mediated seed dispersal, is a diffuse, widespread mutualism in which both partners are purported to benefit from the services or rewards of the other. However, ant benefits in this interaction are conflicted and understudied, especially in the context of microbial third parties. Here, we investigate the effect of a myrmecochore plant-produced antimicrobial chemical (sanguinarine) on the growth of a common entomopathogenic fungus (Beauveria bassiana). We then explore whether sanguinarine, through its effect on entomopathogen growth, might influence ant survival and foraging behavior. At high concentrations, sanguinarine increased the growth of B. bassiana, but fungal growth was not affected at concentrations of sanguinarine near natural levels produced in seeds. When ant colonies were exposed to B. bassiana, survival was not affected by a sanguinarine-supplemented diet. Furthermore, ant foraging patterns (preference for or avoidance of food items with sanguinarine) did not change when ants were exposed to the entomopathogen. Though sanguinarine promotes the growth of an entomopathogen at higher concentrations, which might pose an additional risk for ants in myrmecochory, we assert that social immune behavioral defenses (such as grooming or redispersal of seeds after elaiosome consumption) help ants mitigate this risk. By incorporating a microbial third party into this ant-plant interaction, we seek to more fully understand the risks and benefits provided to both partners in this mutualism. We encourage the investigation of third-party influences in reciprocal pairwise interactions to assist in the understanding of the evolution and persistence of mutualisms.

Designing a two-stage colorimetric sensing strategy based on citrate reduced gold nanoparticles: Sequential detection of Sanguinarine (anticancer drug) and visual sensing of DNA.

Distance dependent optical properties of colloidal gold nanoparticles offer designing of colorimetric sensing modalities for detection of a variety of analytes. Herein, we report a simple and facile colorimetric detection assay for an anti-cancer drug, Sanguinarine (SNG) and Calf Thymus DNA (Ct-DNA) based on citrate reduced gold nanoparticles (CI-Au NPs). The electrostatic interaction between SNG and CI-Au NPs induce aggregation of Au NPs accompanied with visible colour change of colloidal solution. The assay conditions like salt concentration, pH and reaction time had been adjusted to achieve highly sensitive and fast colorimetric response. Furthermore, the optimized CI-Au NPs/SNG sensing system is used for the detection of Ct-DNA based on the mechanism of anti-aggregation of CI-Au NPs. The simultaneous presence of SNG and Ct-DNA prevent aggregation of Au NPs owing to preferential formation of Ct-DNA-SNG intercalation complex and colour of the Au NPs solution tends to remain red, depending on the concentration of Ct-DNA in solution. The degree of aggregation and anti-aggregation of CI-Au NPs was monitored using Transmission electron microscopic (TEM) measurements and UV-Visible spectrophotometry by analysing the ratio of absorptions for aggregated and dispersed Au NPs. The intercalation mode of binding between SNG and Ct-DNA in CI-Au NPs/SNG sensing system was determined by Fluorescence spectral studies and UV-thermal melting studies. The absorption ratio (A627/A525) of Au NPs exhibited a linear correlation with SNG concentrations in the range from 0 to 0.9μM with detection limit as 0.046μM. This optical method can determine Ct-DNA as low as 0.36μM and the calibration is linear for concentration range 0 to 5μM. The proposed sensing strategy enables detection as well as quantification of SNG & Ct-DNA in real samples with satisfactory results and finds application in drug or DNA monitoring.

Dietary sanguinarine supplementation on the growth performance, immunity and intestinal health of grass carp (Ctenopharyngodon idellus) fed cottonseed and rapeseed meal diets

Sanguinarine (SG) is a plant alkaloid with demonstrated anti-inflammatory, antioxidant, and antimicrobial properties. However, its effects on the immunity and intestinal health of grass carp have not been clarified. Herein, an eight-week feeding trial was conducted to evaluate the effects of SG on the growth, immunity, and intestinal health of grass carp (Ctenopharyngodon idellus). A basal diet of 5% fish meal and 44% cottonseed and rapeseed meal was designated as the control diet (FM group). Diets (2% fish meal, 55% cottonseed and rapeseed meal) supplemented with four SG concentrations (0, 0.2, 0.4, and 0.8 g·kg−1; designated as the SG0, SG0.2, SG0.4, and SG0.8 groups, respectively) were prepared. The results indicate that dietary SG in high cottonseed and rapeseed meal diets increased the survival rate (SR), weight gain rate (WGR), superoxide dismutase (SOD), and alkaline phosphatase (AKP) activities compared with the SG0 group, but not significantly. The activity of malondialdehyde (MDA) was significantly lower in the SG0.2–0.8 groups than SG0 group. The SG0 group had a significantly decreased number of goblet cells and villus height/crypt depth (V/C), significantly downregulated mRNA expression levels of MnSOD, claudin, occludin, ZO-1, and ZO-2, and significantly upregulated mRNA expression levels of TNF-α, IL-1β, TLR-7, and TLR-8 compared with those in the FM group. While the number of goblet cells and V/C were significantly greater, the expression of MnSOD, ZO-1, and ZO-2 was significantly upregulated and the mRNA expression levels of TNF-α, IL-1β, IL-6, TLR-4, TLR-7, and TLR-8 were significantly downregulated in the SG0.8 group compared with those in the SG0 group. The proportion of Aeromonas significantly increased, and the Bacteroides significantly decreased in the SG0 group compared with the FM group. However, the proportion of Aeromonas showed significantly decreased, while the proportion of Bacteroides increased in the SG0.8 group compared with the SG0 group. Furthermore, based on microbial function, the gut microbiota of the SG0.8 group were more active concerning the energy, lipid, and amino acid metabolisms compared with those of the SG0 group. In conclusion, the feed with a higher cottonseed and rapeseed meal concentration negatively affects the SR, intestinal structure and immunity of grass carp. However, dietary SG can improve the SR and WGR by enhancing the intestinal morphology, microbiota structure, and mRNA expression levels of genes related to intestinal immunity.

Sanguinarine metabolism and pharmacokinetics study in vitro and in vivo.

Sanguinarine (SA) is a benzo[c] phenanthridine alkaloid which has a variety of pharmacological properties. However, very little was known about the pharmacokinetics of SA and its metabolite dihydrosanguinarine (DHSA) in pigs. The purpose of this work was to study the intestinal metabolism of SA in vitro and in vivo. Reductive metabolite DHSA was detected during incubation of SA with intestinal mucosa microsomes, cytosol, and gut flora. After oral (p.o.) administration of SA, the result showed SA might be reduced to DHSA in pig intestine. After i.m. administration, SA and DHSA rapidly increased to reach their peak concentrations (Cmax , 30.16±5.85, 5.61±0.73ng/ml, respectively) at 0.25hr. Both compounds were completely eliminated from the plasma after 24hr. After single oral administration, SA and DHSA rapidly increased to reach their Cmax (3.41±0.36, 2.41±0.24ng/ml, respectively) at 2.75±0.27hr. The half-life (T1/2 ) values were 2.33±0.11hr and 2.20±0.12hr for SA and DHSA, respectively. After multiple oral administration, the average steady-state concentrations (Css ) of SA and DHSA were 3.03±0.39 and 1.42±0.20ng/ml. The accumulation indexes for SA and DHSA were 1.21 and 1.11. The work reported here provides important information on the metabolism sites and pharmacokinetic character of SA. It explains the reasons for low toxicity of SA, which is useful for the evaluation of its performance.

Sanguinarine Decreases Cell Stiffness and Traction Force and Inhibits the Reactivity of Airway Smooth Muscle Cells in Culture

Airway hyperresponsiveness (AHR) is the cardinal character of asthma, which involves the biomechanical properties such as cell stiffness and traction force of airway smooth muscle cells (ASMCs). Therefore, these biomechanical properties comprise logical targets of therapy. β2-adrenergic agonist is currently the mainstream drug to target ASMCs in clinical practice for treating asthma. However, this drug is known for side effects such as desensitization and non-responsiveness in some patients. Therefore, it is desirable to search for new drug agents to be alternative of β2-adrenergic agonist. In this context, sanguinarine, a natural product derived from plants such as bloodroots, that has been reported to relax gut smooth muscle emerges as a potential candidate. So far, it is unknown whether sanguinarine can regulate the biomechanical properties of ASMCs and reactivity of ASMCs to irritants. Thus, we tested the hypothesis that sanguinarine reduce the contractile potentials of ASMCs in culture. To do so, the primary cultured rat ASMCs were first treated with different concentration of sanguinarine. Then, cell stiffness, traction force, fiber distribution, and calcium signaling of the ASMCs were evaluated by optical magnetic twisting cytometry, Fourier transform traction microscopy, atomic force microscopy, and Fluo-4/AM based fluorescence confocal scanning microscopy, respectively. The results indicated that sanguinarine (0.05 and 0.5 μmol/L) significantly decreased cell stiffness and traction force, inhibited reactivity of ASMCs to histamine, and disrupted the fiber structures in ASMCs in dose-dependent manner. These findings establish that sanguinarine can indeed change the biomechanical properties of ASMCs and may be used to treat AHR in asthma.

Sanguinarine exhibits antitumor activity via up‐regulation of Fas‐associated factor 1 in non‐small cell lung cancer

Lung cancer is the most common type of malignancy and one of the leading causes of cancer-related deaths in the world. Non-small cell lung carcinomas (NSCLC) account for 85% cases of lung cancer. Sanguinarine (SNG) is a benzophenanthridine alkaloid isolated from plants of the Papaveraceae family that possess diverse biological activities. SNG exhibits antitumor effects in several cancer cells. However, the effects of SAN on NSCLC proliferation, invasion, and migration and the mechanisms remain to be clarified. We showed that SNG concentration- and time-dependently decreased the cell proliferation, viability, and induced a marked increase in cell death in A549 cells. SNG inhibited invasion and migration and induced S phase cell cycle arrest and apoptosis. SNG resulted in a significant increase of E-cadherin expression and a marked decrease of the expression of N-cadherin, Vimentin, Smad2/3, and Snail and the phosphorylation of Smad2. SNG increased Fas-associated factor 1 (FAF1) expression and upregulation of FAF1 inhibited cell proliferation, invasion, and migration and induced cell cycle arrest and apoptosis in NSCLC cells. Knockdown of FAF1 suppressed SNG-induced inhibition of cell proliferation, invasion, and migration and induction of cell cycle arrest and apoptosis in NSCLC cells. SNG also inhibited implanted tumor growth and increased FAF1 expression in tumors in vivo. Our findings highlight FAF1 as a novel therapeutic target and provide a new insight in the potential use of SNG for the inhibition of NSCLC.

Safety of standardized Macleaya cordata extract in an eighty-four-day dietary study in dairy cows.

The objective of this study was to evaluate the safety of a standardized Macleaya cordata Extract Product (MCEP) containing the quaternary benzophenanthridine alkaloids, sanguinarine and chelerythrine, when fed to dairy cows. Thirty-six dairy cows were randomized into three groups with twelve cows/treatment in two replica pens for each treatment group: control (C) without MCEP added to feed, treatment 1 (SANG-1000) with MCEP added to feed at 1,000mg/animal/day (1.5mg/kg bw/day) and treatment 2 (SANG-10000) with MCEP added to feed at 10,000mg/animal/day (15.5mg MCEP/kg bw/day). After two weeks of acclimation, animals were observed for an 84-day experimental period, with body weight, feed intake and milk production measured daily. Milk composition was analysed every two weeks. Haematological analyses were performed on Day 0 and Day 84, and clinical chemistry analyses were performed on Day 84 of the study. There was no statistically significant difference (p>.10) among the three groups on body condition score, milk production or milk composition over the study period. There were no significant differences in body weight gain or feed consumption among the three groups. Animals in the SANG-10000 group had significantly higher mean corpuscular volume (MCV) than the C group (p<.1) and lower mean corpuscular haemoglobin concentration (MCHC) than the SANG-1000 group (p<.1). Concentrations of sanguinarine and chelerythrine in milk samples collected on Day 84 were below the detection limit (LOD) as measured by high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS). In conclusion, this study presents compelling data supporting the hypothesis that the test product MCEP, when included in the TMR at up to 10,000mg/animal/day (15.5mg MCEP/kg bw/day), is well tolerated by dairy cows.

Antibacterial efficacy and pharmacokinetic evaluation of sanguinarine in common carp (Cyprinus carpio) following a single intraperitoneal administration

Sanguinarine (SA), with antimicrobial and antiparasitic activities against fish pathogens, exhibits great potential commercial use in aquaculture. However, little information on pharmacokinetics of SA restricts further application in aquaculture. In this study, pharmacokinetics of SA in common carp (Cyprinus carpio) following a single intraperitoneal administration [10mgkg(-1) BW (body weight)] was evaluated by high-performance liquid chromatography (HPLC). The peak concentration (Cmax ) of SA in kidney was 11.8μgg(-1) , which was higher than in other tissues and plasma. The terminal half-life in fish tissue and plasma was as follows: 42.3h (kidney)>37.2h (liver)>20.1h (gill)>18.8h (muscle)>10.9h (spleen)>10.0h (plasma). Additionally, we determined the bacterial loads in tissues of common carp infected with Aeromonas hydrophila after i.p. administration of SA at 0, 5, 10 and 20mgkg(-1) BW. The results showed that i.p. administration of SA at 10mgkg(-1) BW significantly enhanced antibacterial efficacy against A.hydrophila, where the antibacterial ratio in the gill, kidney, spleen and liver on day 5 was 95.13%, 93.33%, 90.09% and92.82%, respectively. Overall, these results suggested the potential of SA to treat A.hydrophila infection in common carp farming industry.

Argemone oil induces genotoxicity in mice

Context: Argemone mexicana L. is native to Mexico and the plant extracts are used in traditional medicine in India and South American countries. Argemone oil (AO) is a common adulterant of mustard oil in India and causes serious pathophysiological consequences leading to outbreaks of epidemic dropsy among consumers. In vivo cytogenetic studies on the toxicological effects of AO and its component alkaloids are limited. Objective: The present study was undertaken to evaluate the safety of AO by assessment of their in vivo genotoxic potential in bone marrow cells of mice. Materials and methods: AO mixed in corn oil in the proportions of 0.01, 0.1, and 1 ml AO/kg body weight in a total volume of 10 ml/kg body weight and a single undiluted dose of AO (10 ml/kg body weight) were administered intraperitoneally in separate groups of male Swiss Albino mice for 24 h. In addition, a single concentration of sanguinarine (SG) (50 mg/kg body weight) was also administered. Genotoxicity was evaluated by chromosome aberration (CA) and sister chromatid exchange (SCE) tests. Bromodeoxyuridine (BrdU) differential technique was used to study the effect on cell replication by the calculation of average generation time (AGT). Results: The minimum effective concentrations that produced significant frequencies of CA and SCE were 0.1 and 0.01 ml/kg, respectively. AO and SG induced an insignificant increase of AGT indicating that they are non-cytotoxic in the concentrations tested.Discussion and conclusion: Our results confirm that AO is genotoxic even at low concentrations and its usage should be checked.

The cytotoxic activity of sanguinarine in C32 human amelanotic melanoma cells

Sanguinarine, an alkaloid present in various medicinal plants, has been associated with detrimental effects on different types of cancer cells. The aim of our study was to analyze the cytotoxic effects of sanguinarine on C32 human amelanotic melanoma cells. The cells were exposed to various concentrations of sanguinarine (0.5, 1, and 2 μM) for 24 h and displayed a dose-dependent decrease in cell viability; the sanguinarine-induced oxidative stress in C32 cells affected the activity of antioxidant enzymes and generated lipid peroxidation. Moreover, we observed an enhanced expression of heat shock proteins 60, 70, and 90 in response to the stress exerted by this alkaloid. The increased p53 protein expression and Bax/Bcl-2 ratio revealed the susceptibility of C32 cells to apoptosis. Our study demonstrated that sanguinarine induced cytotoxicity in melanoma cells that ultimately resulted in cell death. These results emphasize the antigrowth efficiency of sanguinarine against amelanotic melanoma cells, but further research is needed in order to obtain more potent antitumor effects of this alkaloid.

AGS 인체 위암세포에서 DR5의 발현 및 ROS 생성의 증가를 통한 sanguinarine과 TRAIL 혼합처리의 apoptosis 유도 활성 촉진

혈근초(Sanguinaria canadensis) 뿌리에서 유래된 benzophenanthridine alkaloid의 일종인 sanguinarine은 항균, 항산화 및 항암작용 등 다양한 생리활성을 지니고 있는 것으로 알려져 있다. 비록 TRAIL이 암세포에서는 apoptosis를 유도하지만 정상세포에서는 세포독성을 나타내지 않는다는 큰 장점으로 제 2 임상 단계에서 유의적인 성과를 이루었지만, TRAIL 저항성을 극복해야 하는 큰 어려움이 남아있다. 본 연구실에서는 TRAIL이 세포독성을 나타내지 않는 범위의 sanguinarine과 혼합처리에 의하여 TRAIL 저항성 AGS 위암세포에서 apoptosis를 유발하였음을 보고한 바 있으며, 본 연구에서는 sanguinarine의 TRAIL 저항성 관련 극복에 대한 추가적인 기전 연구를 실시하였다. 본 연구의 결과에 의하면, sanguinarine과 TRAIL의 혼합처리는 각각의 단독 처리에 비하여 AGS 세포의 증식억제 및 apoptosis 유도의 상승 효과가 있었으며, 이를 MTT assay, agarode gel 전기영동, 염색질 응축 현상 및 flow cytometry 분석을 통하여 확인하였다. 또한 sanguinarine과 TRAIL의 혼합처리는 DR5의 발현을 증가시켰으며, ROS의 생성을 촉진시켰다. 그러나 동일 조건에서 MAPKs 신호 전달계에는 큰 영향을 주지 않았다. 아울러 ROS 생성을 인위적으로 차단하였을 경우, sanguinarine과 TRAIL의 혼합처리에 의한 생존도 저하가 유의적으로 회복되었다. 이러한 결과는 sanguinarine과 TRAIL이 DR5의 발현 증가와 ROS의 생성을 촉진시킴으로서 apoptosis 신호를 활성화하였음을 의미하는 결과로서 TRAIL 저항성 극복을 위한 sanguinarine 활용의 유용성을 보여주는 것이다. Sanguinarine, a benzophenanthridine alkaloid originally derived from the root of Sanguinaria canadensis, has been shown to possess antimicrobial, antioxidant, and anti-cancer properties. Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is known to induce apoptosis in cancer cells, but not most normal cells and has shown efficacy in a phase 2 clinical trial, development of resistance to TRAIL by tumor cells is a major roadblock. Our previous study indicated that treatment with TRAIL in combination with subtoxic concentrations of sanguinarine sensitized TRAIL-mediated apoptosis in TRAIL-resistant human gastric carcinoma AGS cells; however, the detailed mechanisms are not fully understood. In this study, we show that sanguinarine sensitizes AGS cells to TRAIL-mediated apoptosis as detected by MTT assay, agarose gel electrophoresis, chromatin condensation and flow cytometry analysis. Combined treatment with sanguinarine and TRAIL effectively induced expression of death receptor (DR) 5 but did not affect expression of DR4 and mitogen activated protein kinases signaling molecules. Moreover, the combined treatment with sanguinarine and TRAIL increased the generation of reactive oxygen species (ROS); however, N-acetylcysteine, ROS scavenger, significantly recovered growth inhibition induced by the combined treatment. Taken together, our results indicate that sanguinarine can potentiate TRAIL-mediated apoptosis through upregulation of DR5 expression and ROS generation.

Fluorescence quenching investigation on the interaction of glutathione‐CdTe/CdS quantum dots with sanguinarine and its analytical application

Water-soluble glutathione (GSH)-capped core/shell CdTe/CdS quantum dots (QDs) were synthesized. In pH5.4 sodium phosphate buffer medium, the interaction between GSH-CdTe/CdS QDs and sanguinarine (SA) was investigated by spectroscopic methods, including fluorescence spectroscopy and ultraviolet-visible absorption spectroscopy. Addition of SA to GSH-CdTe/CdS QDs results in fluorescence quenching of GSH-CdTe/CdS QDs. Quenching intensity was in proportion to the concentration of SA in a certain range. Investigation of the quenching mechanism, proved that the fluorescence quenching of GSH-CdTe/CdS QDs by SA is a result of electron transfer. Based on the quenching of the fluorescence of GSH-CdTe/CdS QDs by SA, a novel, simple, rapid and specific method for SA determination was proposed. The detection limit for SA was 3.4 ng/mL and the quantitative determination range was 0.2-40.0 µg/mL with a correlation coefficient of 0.9988. The method has been applied to the determination of SA in synthetic samples and fresh urine samples of healthy human with satisfactory results.

Molecular basis of recognition of quadruplexes human telomere and c-myc promoter by the putative anticancer agent sanguinarine

BackgroundInteraction of putative anticancer agent sanguinarine with two quadruplex forming sequences, human telomeric DNA (H24) and NHE III1 upstream of the P1 promoter of c-myc (Pu27), has been studied to understand the structural basis of the recognition. MethodsAbsorption, fluorescence and circular dichroism spectroscopy have been employed to characterize the association. Energetics of the interaction was studied by isothermal titration and differential scanning calorimetry. TRAP assay was done to assess the inhibitory potential of sanguinarine. ResultsAbsorption and fluorescence studies show that sanguinarine has high binding affinity of ~105M−1 for both sequences. Binding stoichiometry is 2:1 for H24 and 3:1 for Pu27. Results suggest stacking interaction between planar sanguinarine moiety and G-quartets. Circular dichroism spectra show that sanguinarine does not cause structural perturbation in the all-parallel Pu27 but causes a structural transition from mixed hybrid to basket form at higher sanguinarine concentration in case of H24. The interaction is characterized by total enthalpy–entropy compensation and high heat capacity values. Differential scanning calorimetry studies suggest that sanguinarine binding increases the melting temperature and also the total enthalpy of transition of both quadruplexes. TRAP results show that sanguinarine effectively blocks telomerase activity in a concentration dependent manner in cell extracts from MDAMB-231 breast cancer cell lines. ConclusionThese results suggest that there is a difference in the structural modes of association of sanguinarine to the quadruplexes. General significanceIt helps to understand the role of quadruplex structures as a target of small molecule inhibitors of telomerase.

Association of Mustard Oil as Cooking Media with Carcinoma of the Gallbladder

Carcinoma of the gallbladder (CaGB) is a common health problem in Northern India. Exact causative factors are still obscure. Dietary habits are also known to be a major factor in the gallbladder carcinogenesis. Mustard oil is mostly used as cooking media, which is adulterated by sanguinarine, diethylnitrosamine and repeated frying. We tried to find out the association of mustard oil as cooking media with CaGB. Twenty patients each of CaGB (group I) and cholelithiasis (group II) were included in the study. Sanguinarine and diethylnitrosamine (DEN) were extracted from the tissue and blood samples from both groups. Mean and standard error of mean of the concentration of the sanguinarine and DEN were calculated. Mann-Whitney U test was applied to test the level of significance between the two groups. The mean concentration of tissue sanguinarine in both groups (I and II) was 195.18 ng/mg and 24.05 ng/mg, respectively, and the difference was statistically highly significant (p < 0.001). The estimated concentration of blood sanguinarine was 230.96 ng/mL and 14.0 ng/mL in group I and II, respectively, and the difference was statistically highly significant (p < 0.001). The concentration of DEN in the tissue sample was 38.08 ng/mg in CaGB and 2.51 ng/mg in cholelithiasis patient, and these values were statistically highly significant (p < 0.001). Similarly, blood DEN concentration was 119.05 ng/mL and 4.22 ng/mL in group I and II, respectively, and the difference was statistically highly significant (p < 0.001). There is an increase in concentration of sanguinarine and diethylnitrosamine in CaGB blood and tissue in comparison to the cholelithiasis group suggesting an association with carcinoma of the gallbladder.

Insights into Anti Cancer Agent‐Induced Cardiotoxicity

Anti cancer therapy is often complicated by the development of toxicity to the heart. Cardiotoxicity due to anti neoplastic therapy is important to recognize and address as this may have a significant impact on the overall prognosis and survival of those patients. Recent studies have explored the relationship of cardiomyocyte cell injury to the major modes of cell death, and it appears that cardiomyocyte cell injury involves the pathways of apoptosis and oncosis. We have found sanguinarine, a known anticancer agent, to induce apoptosis and oncosis in several malignant cell lines when treated with concentrations of 1.5 μg/ml and 25 μg/ml, respectively. Furthermore, a similar biphasic pattern of cell death was observed when cultured primary cardiomyocytes were treated with the same sanguinarine concentrations. Using this primary cardiomyocyte cell model we proceeded to study the molecular expression profile of oncosis. Microarray analysis of 4 repeated experiments revealed altered expression of 2514 probes in sanguinarine‐induced oncosis (p value &lt;0.001). The pathways involved include mitochondrial dysfunction, fatty acid metabolism, p53 signaling and oxidative phosphorylation. The discovery of novel oncosis‐related molecules could facilitate the development of more effective therapeutics to combat and prevent chemotherapeutic cardiotoxicity.

782 SANGUINARINE INHIBITS STAT3 ACTIVATION AND TUMOR GROWTH IN PROSTATE CANCER CELLS

You have accessJournal of UrologyProstate Cancer: Basic Research IV1 Apr 2012782 SANGUINARINE INHIBITS STAT3 ACTIVATION AND TUMOR GROWTH IN PROSTATE CANCER CELLS Meng Sun, Chengfei Liu, Wei Lou, Nagalakshmi Nadiminty, Joy Yang, Christopher Evans, and Allen Gao Meng SunMeng Sun Sacramento, CA More articles by this author , Chengfei LiuChengfei Liu Sacramento, CA More articles by this author , Wei LouWei Lou Sacramento, CA More articles by this author , Nagalakshmi NadimintyNagalakshmi Nadiminty Sacramento, CA More articles by this author , Joy YangJoy Yang Sacramento, CA More articles by this author , Christopher EvansChristopher Evans Sacramento, CA More articles by this author , and Allen GaoAllen Gao Sacramento, CA More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.870AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Signal Transducer and Activator of Transcription 3 (STAT3) is an oncogenic transcription factor implicated in prostate carcinogenesis and progression. Stat3 activation is associated with prostate cancer development and progression. Constitutively activated Stat3 activates androgen receptor signaling and promotes castration-resistant prostate cancer growth. Targeting Stat3 activation is an effective strategy in prostate cancer therapy. METHODS DU145, C4-2B and LNCaP cells were treated with sanguinarine for 4 hours and then stimulated with Interleukin-6 (IL-6) or vehicle. The phosphorylation status of STAT3 and related proteins were measured with western blots. Activation of transcription by STAT3 via the STAT3 responsive element was measured with luciferase reporter assay. The effect of sanguinarine on DU145 and LN/S17 cells anchorage-independent growth were examined with soft agar assay. The effect of sanguinarine on cells migration and invasion of DU145 cells were measured with scratch assay and invasion assay respectively. RESULTS Exposure to micromolar concentrations of sanguinarine resulted in suppression of constitutive as well as IL6-induced phosphorylation of STAT3 at both Tyr705 and Ser727 in DU145 cells. The inhibition of STAT3 phosphorylation correlated with the inhibition of Janus-activated Kinase 2 (JAK2) and src phosphorylation. Sanguinarine inhibited the constitutive and IL6-induced STAT3 responsive element luciferase activities. Several STAT3 regulated genes such as c-myc and survivin were downregulated by sanguinarine. We found that sanguinarine inhibited the migration and invasion of DU145 cells that express constitutively activated STAT3. Furthermore, sanguinarine inhibited the anchorage-independent growth of DU145 and LN/S17 cells and suppressed the growth of DU145 xenografts in nude mice. CONCLUSIONS These data suggest that sanguinarine targets multiple upstream kinases that mediate STAT3 activity. Sanguinarine is a potent STAT3 inhibitor that could be developed as a therapeutic agent for prostate cancer. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e320 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Meng Sun Sacramento, CA More articles by this author Chengfei Liu Sacramento, CA More articles by this author Wei Lou Sacramento, CA More articles by this author Nagalakshmi Nadiminty Sacramento, CA More articles by this author Joy Yang Sacramento, CA More articles by this author Christopher Evans Sacramento, CA More articles by this author Allen Gao Sacramento, CA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...