Resveratrol imparts photoprotection of normal cells and enhances the efficacy of radiation therapy in cancer cells

Solar radiation spans a whole range of electromagnetic spectrum including UV radiation, which are potentially harmful to normal cells as well as ionizing radiations which are therapeutically beneficial towards the killing of cancer cells. UV radiation is an established cause of a majority of skin cancers as well as precancerous conditions such as actinic keratosis. However, despite efforts to educate people about the use of sunscreens and protective clothing as preventive strategies, the incidence of skin cancer and other skin-related disorders are on the rise. This has generated an enormous interest towards finding alternative approaches for management of UV-mediated damages. Chemoprevention via nontoxic agents, especially botanical antioxidants, is one such approach that is being considered as a plausible strategy for prevention of photodamages including photocarcinogenesis. In this review, we have discussed the photoprotective effects of resveratrol, an antioxidant found in grapes and red wine, against UVB exposure-mediated damages in vitro and in vivo. In addition, we have also discussed studies showing that resveratrol can act as a sensitizer to enhance the therapeutic effects of ionizing radiation against cancer cells. Based on available literature, we suggest that resveratrol may be useful for (1) prevention of UVB-mediated damages including skin cancer and (2) enhancing the response of radiation therapies against hyperproliferative, precancerous and neoplastic conditions.     

Combination of the advantages of chromatographic methods based on active components for the quality evaluation of licorice

A rapid, improved and comprehensive method including high‐performance thin‐layer chromatography, fingerprint technology and single standard to determine multiple components was developed and validated for the quality evaluation of licorice. In this study, a newly developed high‐performance thin‐layer chromatography method was first used for authentication of licorice, which achieved simultaneous identification of multiple bands including five bands for known bioactive components by comparing their retention factor values and colors with the standards. For fingerprint analysis, 8 of 16 common peaks were identified. Simultaneously, similarity analysis which showed very similar patterns and hierarchical clustering analysis were performed to discriminate and classify the 27 batches of samples. Additionally, the single standard to determine multiple components method was first successfully achieved to quantify the eight important active markers in licorice including liquiritin apioside, liquiritin, isoliquiritin apioside, isoliquritin, neoisoliquiritin, liquiritigenin, isoliquiritigenin and glycyrrhizic acid. The easily available glycyrrhizic acid was selected as the reference substance to calculate relative response factors. Compared with the normal external standard method, this alternative method can be used to determine the multiple indices effectively and accurately. The validation result showed that the developed method was specific, accurate, precise, robust and reliable for the overall quality assessment of licorice.     

Analysis of the active components of silymarin

Silymarin is an antihepatotoxic substance isolated from fruits of Silybum marianum. Possibly due to their antioxidant and membrane stabilizing properties, the compounds have been shown to protect different organs and cells against a number of insults. The content and composition of main silymarin components (silybin, isosilybin, silydianin and silychristin) in various pharmaceuticals were analysed using HPLC and newly developed capillary zone electrophoresis method. Antioxidant properties expressed as total antioxidant status (TAS) of silymarin components were studied. Results of TAS were correlated with electropherograms and chromatograms.     

Natural compounds with proteasome inhibitory activity for cancer prevention and treatment

The proteasome is a multicatalytic protease complex that degrades most endogenous proteins including misfolded or damaged proteins to ensure normal cellular function. The ubiquitin-proteasome degradation pathway plays an essential role in multiple cellular processes, including cell cycle progression, proliferation, apoptosis and angiogenesis. It has been shown that human cancer cells are more sensitive to proteasome inhibition than normal cells, indicating that a proteasome inhibitor could be used as a novel anticancer drug. Indeed, this idea has been supported by the encouraging results of the clinical trials using the proteasome inhibitor Bortezomib (Velcade, PS-341), a drug approved by the US Food and Drug Administration (FDA). Several natural compounds, including the microbial metabolite lactacystin, green tea polyphenols, and traditional medicinal triterpenes, have been shown to be potent proteasome inhibitors. These findings suggest the potential use of natural proteasome inhibitors as not only chemopreventive and chemotherapeutic agents, but also tumor sensitizers to conventional radiotherapy and chemotherapy. In this review, we will summarize the structures and biological activities of the proteasome and several natural compounds with proteasome inhibitory activity, and will discuss the potential use of these compounds for the prevention and treatment of human cancers.     

模拟体内微环境筛选与肿瘤细胞作用的中药活性成分

利用三维(3D)细胞反应器模拟体内微环境,建立了一种与肿瘤细胞作用的活性分子的筛选和分析方法.利用药物与三维细胞反应器中活肿瘤细胞和固化肿瘤细胞分别作用后的HPLC生物指纹谱峰面积之间有无显著性差异,建立了与细胞结合的活性成分的筛选识别模型.已知抗肿瘤药物紫杉醇和白藜声醇的谱峰均具有显著性差异,而非抗肿瘤药物酮洛芬和青霉素G的谱峰均没有显著性差异,证明利用该模型筛选识别与细胞结合的活性成分是可行的.此外,应用该模型从中草药桃儿七提取物中筛选出了7种可作用于Lovo细胞的活性成分.此研究提供了一种模拟体内微环境下与肿瘤细胞作用的活性成分的筛选和分析方法,在药物发现环节,特别是中草药活性成分研究中具有潜在的应用价值.     

Enhancement of radiosensitivity by combined ceramide and dimethylsphingosine treatment in lung cancer cells

Ceramide generated from sphingomyelin in response to ionizing radiation has been implicated as a second messenger to induce cellular proapoptotic signals. Both ceramide and its metabolic inhibitor, N, N-dimethyl-D-erythro-sphingosine (DMS), might lead to sustained ceramide accumulation in cells more efficiently, thereby sensitizing them to gamma-radiation-induced cell death. To delineate this problem, the clonogenic survival of Lewis lung carcinoma (LLC) cells was evaluated following exposure to radiation together with or without C2-ceramide, DMS, or both. The treatment of ceramide/DMS synergistically decreased the survival of the irradiated cells compared with treatment with ceramide or DMS alone. Ceramide/DMS-treated cells displayed several apoptotic features after gamma-irradiation, including increased sub G(1) population, TUNEL-positive fraction, and poly-(ADP-ribose) polymerase (PARP) cleavage. We also observed ceramide/ DMS induced disruption of mitochondrial membrane potential (MMP) and activation of caspase- 9 and -3 in a radiation-dose-dependent manner. Furthermore, pretreatment of LLC cells with ceramide/DMS not only increased the protein expression level of Bax, but also decreased Bcl-2 after gamma-irradiation. Taken together, the present study indicates that the radiosensitizing activity of ceramide/DMS on LLC cells most likely reflects the dominance of pro-apoptotic signals related to the mitochondria-dependent pathway.     

Preparation and properties of inhalable nanocomposite particles for treatment of lung cancer

Nanoparticles have widely been studied in drug delivery research for targeting and controlled release. The aim of this article is application of nanoparticles as an inhalable agent for treatment of lung cancer. To deposit effectively deep the particles in the lungs, the PLGA nanoparticles loaded with the anticancer drug 6-{[2-(dimethylamino)ethyl]amino}-3-hydroxyl-7H-indeno[2,1-c]quinolin-7-one dihydrochloride (TAS-103) were prepared in the form of nanocomposite particles. The nanocomposite particles consist of the complex of drug-loaded nanoparticles and excipients. In this study, the anticancer effects of the nanocomposite particles against the lung cancer cell line A549. Also, the concentration of TAS-103 in blood and lungs were determined after administration of the nanocomposite particles by inhalation to rats.TAS-103-loaded PLGA nanoparticles were prepared with 5% and 10% of loading ratio by spray drying method with trehalose as an excipient. The 5% drug-loaded nanocomposite particles were more suitable for inhalable agent because of the sustained release of TAS-103 and higher FPF value. Cytotoxicity of nanocomposite particles against A549 cells was higher than that of free drug.When the nanocomposite particles were administered in rats by inhalation, drug concentration in lung was much higher than that in plasma. Furthermore, drug concentration in lungs administered by inhalation of nanocomposite particles was much higher than that after intravenous administration of free drug.From these results, the nanocomposite particle systems could be promising for treatment of lung cancer.     

Determination of the biologically active components of the rhizomes of Rhodiola rosea

A chromato-spectrometric method for the quantitative determination of the total cinnamyl glycosides and salidroside in the raw material of roseroot stonecrop using a standard sample of rosavin has been developed.All-Union Scientific-Research Institute of Medicinal Plants Scientific Production Combine, Moscow. Translated from Khimiya Prirodnykh Soedinenii, No. 3, pp. 320–323, May–June, 1991.     

Photodynamic therapy with pyropheophorbide-a methyl ester in human lung carcinoma cancer cell: efficacy,localization and apoptosis

Pyropheophorbide-a methyl ester (MPPa) is a semisynthetic photosensitizer derived from chlorophyll a. The absorption peak of MPPa in organic solvent and in cells was at 667 and 674 nm, respectively. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction assay showed that MPPa had no dark cytotoxicity. In vitro photodynamic activity was extensively evaluated using a human lung carcinoma cancer cell line (NCI-h446). MPPa exhibited no genotoxicity, as assayed by single-cell gel electrophoresis. Using confocal laser scanning microscopy and organelle-specific fluorescent probes, MPPa was found to localize in the intracellular membrane system, namely the endoplasmic reticulum, Golgi apparatus, lysosomes and mitochondria, in the NCI-h446 cells. Furthermore, nuclear staining and DNA gel electrophoresis revealed that DNA condensation and fragmentation occurred post-photodynamic therapy, indicating the cell death was in the apoptotic mode.     

Use of an ion-selective membrane electrode for the determination of the active components in intestopan

The conditions for the determination of broxyquinoline and brobenzoxaldine, the active components of "Intestopan", by use of ion-selective membrane electrodes are described. Broxyquinoline is determined directly through precipitation with CuSO(4), and brobenzoxaldine is first hydrolysed in alkaline solution and the product precipitated with CuSO(4). In both cases the CuSO(4) in excess is determined by potentiometric titration at pH 5.6 with EDTA, a Cu(2+)-selective electrode being used for end-point detection.     

Determination of active components in Chinese medicinal preparations by capillary electrophoresis

The determination of paeoniforin, paeonol, and censenoside Rg₁ in traditional Chinese medicinal preparations, Tze Po San Pien pills and Liuwen Dihuang pills has been investigated by micellar electrokinetic capillary electrophoresis with borate buffer (20 mM), sodium dodecylsulfate (30 mM) and acetonitrile (20%) as background electrolytes (pH 9.30), 20 kV applied voltage and 203 nm UV detection. The effects of SDS concentration, borate, buffer pH, and organic modifier on electrophoretic behavior and separation are discussed. Regression equations revealed linear relationships between the peak-area of each component and the content with the correlation coefficients from 0.9982 to 0.9999. In addition, the levels of the active compounds in two kinds of traditional Chinese medicinal preparations were easily determined with the recoveries from 93.1% to 108.2%.      

Use of antioxidants in the prevention and treatment of disease.

Considerable interest has risen in the idea that oxidative stress is instrumental in the etiology of numerous human diseases. Oxidative stress can arise through the increased production of reactive oxygen species (ROS) and/or because of a deficiency of antioxidant defenses. Antioxidant deficiencies can develop as a result of decreased antioxidant intake (such as vitamins C and E), synthesis of enzymes (such as superoxide dismutase and glutathione peroxidase) or increased antioxidant utilization. Insufficient antioxidant enzyme synthesis may in turn be due to decreased micronutrient availability (such as selenium, magnese, copper and zinc). Of those diseases linked with oxidative stress, cardiovascular disease provides the strongest evidence for the protective role of antioxidants. A high consumption of fruit and vegetables, which are good sources of antioxidants, is associated with a lower coronary risk. More specifically, there is evidence of a reduced coronary risk in populations with high blood levels of the antioxidant nutrients, vitamins C and E. Evidence is also accumulating that diabetes, and microvascular complications associated with diabetes, involve oxidative stress and have compromised antioxidant status. In addition, patients who develop acute respiratory distress syndrome (ARDS) also exhibit clear evidence of oxidative stress. Definitive proof for active oxygen formation and oxidative cell damage being causative rather than a result of other underlying these pathologies remains elusive; however, evidence is sufficiently compelling to suggest that antioxidants are potential therapeutic agents in the above conditions.     

Positive surface charge enhances selective cellular uptake and anticancer efficacy of selenium nanoparticles

Surface charge plays a key role in cellular uptake and biological actions of nanomaterials. Selenium nanoparticles (SeNPs) are novel Se species with potent anticancer activity and low toxicity. This study constructed positively charged SeNPs by chitosan surface decoration to achieve selective cellular uptake and enhanced anticancer efficacy. The results of structure characterization revealed that hydroxyl groups in chitosan reacted with SeO(3)(2-) ion to form special chain-shaped intermediates, which could be decomposed to form crystals upon reduction by ascorbic acid. The initial colloids nucleated and then assembled into spherical SeNPs. The positive charge of the NH(3)(+) group on the outer surface of the nanoparticles contributed to the high stability in aqueous solutions. Moreover, a panel of four human cancer cell lines were found to be susceptible to SeNPs, with IC(50) values ranging from 22.7 to 49.3 μM. Chitosan surface decoration of SeNPs significantly enhanced the selective uptake by endocytosis in cancer cells and thus amplified the anticancer efficacy. Treatment of the A375 melanoma cells with chitosan-SeNPs led to dose-dependent apoptosis, as evidenced by DNA fragmentation and phosphatidylserine translocation. Our results suggest that the use of positively charged chitosan as a surface decorator could be a simple and attractive approach to achieve selective uptake and anticancer action of nanomaterials in cancer cells.     

Phospholipid dynamics in ex vivo lung cancer and normal lung explants

In cancer cells, metabolic pathways are reprogrammed to promote cell proliferation and growth. While the rewiring of central biosynthetic pathways is being extensively studied, the dynamics of phospholipids in cancer cells are still poorly understood. In our study, we sought to evaluate de novo biosynthesis of glycerophospholipids (GPLs) in ex vivo lung cancer explants and corresponding normal lung tissue from six patients by utilizing a stable isotopic labeling approach. Incorporation of fully ¹³C-labeled glucose into the backbone of phosphatidylethanolamine (PE), phosphatidylcholine (PC), and phosphatidylinositol (PI) was analyzed by liquid chromatography/mass spectrometry. Lung cancer tissue showed significantly elevated isotopic enrichment within the glycerol backbone of PE, normalized to its incorporation into PI, compared to that in normal lung tissue; however, the size of the PE pool normalized to the size of the PI pool was smaller in tumor tissue. These findings indicate enhanced PE turnover in lung cancer tissue. Elevated biosynthesis of PE in lung cancer tissue was supported by enhanced expression of the PE biosynthesis genes ETNK2 and EPT1 and decreased expression of the PC and PI biosynthesis genes CHPT1 and CDS2, respectively, in different subtypes of lung cancer in publicly available datasets. Our study demonstrates that incorporation of glucose-derived carbons into the glycerol backbone of GPLs can be monitored to study phospholipid dynamics in tumor explants and shows that PE turnover is elevated in lung cancer tissue compared to normal lung tissue.Subject terms: Cancer metabolism, Lung cancer     

Identification and screening of active components from Ziziphora clinopodioides Lam. in regulating autophagy

This study investigated the flavonoid constituents of a traditional Chinese medical plant Ziziphora clinopodioides Lam. by using ultra-performance liquid chromatography coupled with quadruple time-of-flight mass spectrometry and screened the active components in regulating autophagy.Normal rat kidney (NRK) cells transfected with green fluorescent protein- microtubule-associated protein 1 light Chain 3(GFP-LC3) were treated with Z. clinopodioides flavonoids and its chemical compositions. After 4 h of treatment, the auto-phagy spot aggregation in NRK cells was photographed and observed by laser scanning confocal microscopy. The following 10 flavonoid components of Z. clinopodioides were identified: baicalein(1), quercetin(2), hyperoside(3), quercetin3-O-β-d-glucopyranoside(4), apigenin(5), kaempferol(6), chrysin(7), diosimin(8), linarin(9) and rutin(10). Among these flavonoids, chrysin, apigenin and quercetin were identified as the active principles in activating autophagy. This research may provide a reference for further developing and utilizing Z. clinopodioides.     

Oridonin nanosuspension enhances anti-tumor efficacy in SMMC-7721 cells and H22 tumor bearing mice

PurposeThe aim of the present study was to evaluate both the in vitro and in vivo antitumor activity of an oridonin nanosuspension (ORI-N) relative to efficacy of bulk oridonin delivery.MethodsORI-N with a particle size of 897.2 ± 14.2 nm and a zeta potential of −21.8 ± 0.8 mV was prepared by the high-pressure homogenization (HPH) technique. The in vitro cytotoxicity of ORI-N against SMMC-7721 cells was evaluated by MTT[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, the effects of ORI-N on cell cycle and cell apoptosis was analyzed by flow cytometry; the in vivo anti-tumor activity was observed in H22 tumor bearing mice.ResultsORI-N effectively inhibited the proliferation of SMMC-7721 cells. Flow cytometric analysis demonstrated that ORI-N arrested SMMC-7721 cells in the G2/M cycle, and furthermore, that ORI-N induced a higher apoptotic rate than the bulk ORI solution. In vivo studies ORI-N also showed higher antitumor efficacy as measured by reduced tumor volume and tumor weight, as well as lower toxicity in H22 solid tumor bearing mice compared to free ORI at the same concentration.ConclusionsThese results suggest that the delivery of ORI-N as a nanosuspension is a promising approach for treating tumors.     

Potentiometric sensors based on new active components in the multisensor determination of homologues anionic surfactants

Potentiometric sensors are proposed on the basis of alkyl sulfates and cationic copper(II) complexes with organic reagents selective to anionic surfactants. Physical and chemical properties of the ionophores (composition, thermal stability, solubility) are determined in aqueous solutions and in the membrane phase. The studied compounds are poorly soluble (K _s = n × 10^–22–n × 10^–20) and thermally stable at 80?90°C. The main electroanalytical properties of sensors are estimated, i.e., analytical range in solutions of sodium alkyl sulfates 2 × 10^–7–1 × 10^–2 M; 46 <α < 66 mV/рc; LOD = 1 × 10^–7 M; response time 8–9 s in a solution of sodium dodecyl sulfate with the concentration not lower than 1 × 10^–4 M; potential drift 2–3 mV/day; and lifetime 12 months. The multisensor determination of homologues sodium alkyl sulfates in model mixtures and natural waters is performed using the proposed sensors.