1-1-diphenyl-2-picrylhydrazyl and Breast-Neoplasms

Rosin (Colophony) is a natural resin derived from species of the pine family Pinaceae. It has wide industrial applications including printing inks, photocopying paper, adhesives and varnishes, soap and soda. Rosin and its derivatives are employed as ingredients in various pharmaceutical products such as ointments and plasters. Rosin-based products contain allergens that may exert some occupational health problems such as asthma and contact dermatitis.. Our knowledge of the pharmaceutical and medicinal properties of rosin is limited. The current study aims at investigating the cytotoxic potential of Rosin-Derived Crude Methanolic Extract (RD-CME) and elucidation of its mode-of-action against breast cancer cells (MCF-7 and MDA-MB231).. Crude methanol extract was prepared from rosin. Its phenolic contents were analyzed by Reversed- Phase High-Performance Liquid Chromatography (RP-HPLC). Antioxidant activity was evaluated by DPPH radical-scavenging assay. Antiproliferation activity against MCF-7 and MDA-MB231 cancerous cells was investigated by MTT assay; its potency compared with doxorubicin as positive control and specificity were assessed compared to two non-cancerous cell lines (BJ-1 and MCF-12F). Selected apoptosis protein markers were assayed by western blotting. Cell cycle analysis was performed by Annexin V-FITC/PI FACS assay.. RD-CME exhibited significant and selective cytotoxicity against the two tested breast cancer cells (MCF-7 and MDA-MB231) compared to normal cells as revealed by MTT assay. ELISA and western blotting indicated that the observed antiproliferative activity of RD-CME is mediated via the engagement of an intrinsic apoptosis signaling pathway, as judged by enhanced expression of key pro-apoptotic protein markers (p53, Bax and Casp 3) relative to vehicle solvent-treated MCF-7 control cells.. To our knowledge, this is the first report to investigate the medicinal anticancer and antioxidant potential of crude methanolic extract derived from colophony rosin. We provided evidence that RD-CME exhibits strong antioxidant and anticancer effects. The observed cytotoxic activity against MCF-7 is proposed to take place via G2/M cell cycle arrest and apoptosis. Colophony resin has a great potential to join the arsenal of plantderived natural anticancer drugs. Further thorough investigation of the potential cytotoxicity of RD-CME against various cancerous cell lines is required to assess the spectrum and potency of its novel activity.

Topics: Antineoplastic Agents, Phytogenic; Antioxidants; Apoptosis; Biphenyl Compounds; Breast Neoplasms; Cell Proliferation; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Gingiva; Humans; Methanol; Molecular Structure; Picrates; Resins, Plant; Structure-Activity Relationship; Tumor Cells, Cultured

Linalool is a monoterpene alcohol which occurs naturally in several aromatic plants. The aims of this study are to load Linalool on gold nanoparticles, conjugate the complex with CALNN peptide, and investigate them for in-vitro anticancer activities against breast cancer (MCF-7) cell line. Linalool was obtained with 98% purity while gold nanoparticles and CALNN peptide were chemically synthesized. The formation of LIN-GNPs and LIN-GNPs-CALNN was observed through a color change. These compounds were confirmed and characterized using SEM, DLS, AFM, UV-VIS spectrophotometer, XRD, and FTIR. The free radical scavenging potential of each compound was confirmed based on its stable antioxidant effects using different parameters. Blood compatibility on red blood cells was confirmed by hemolytic and in vitro cytotoxicity assays. The in-vitro anticancer activity of each compound towardMCF-7 cell line was investigated using various parameters. From the results, Linalool, GNPs, LIN-GNPs, and LIN-GNPs-CALNN were found to exert cell growth arrest against MCF-7 cell line. The anti-proliferative effect of these compounds was due to cell death and induction of apoptosis confirmed using acridine orange-Ethidium bromide dual staining, DAPI staining, and electrophoresis analysis of DNA fragmentation. High fluorescent signals specific for the cellular uptake of LIN-GNPs and LIN-GNPs-CALNN into the cytoplasm of the cell line were confirmed. To study the toxicity of LIN-GNPs-CALNN in animal models, the hematological, histopathological, and body weight changes were estimated after 4 weeks of intraperitoneal injection of the compounds into the animal models. Our results demonstrate that Linalool, GNPs, Linalool-GNPs, and Linalool-GNPs-CALNN peptide had no side effects and could be clinically used for future therapeutic purposes.

Topics: Acyclic Monoterpenes; Animals; Antineoplastic Agents; Antioxidants; Biphenyl Compounds; Blood Cells; Breast Neoplasms; Cell Death; Cell Nucleus Shape; Cell Proliferation; DNA Fragmentation; Drug Delivery Systems; Dynamic Light Scattering; Endocytosis; Female; Gold; Hemolysis; Humans; Hydroxyl Radical; MCF-7 Cells; Metal Nanoparticles; Mice, Inbred BALB C; Monoterpenes; Peptides; Picrates; Spectrophotometry, Ultraviolet; Spectroscopy, Fourier Transform Infrared; X-Ray Diffraction

The anticancer activity of acridone derivatives has attracted increasing interest, therefore, a variety of substituted analogs belonging to this family have been developed and evaluated for their anti-cancer properties. A series of

Topics: Acridines; Acridones; Benzothiazoles; Biphenyl Compounds; Breast Neoplasms; Cell Survival; DNA; DNA Topoisomerases, Type I; Female; Free Radical Scavengers; Humans; MCF-7 Cells; Picrates; Sulfonic Acids; Wound Healing

Nineteen organoselenides were synthesized and tested for their intrinsic cytotoxicity in hepatocellular carcinoma (HepG2) and breast adenocarcinoma (MCF-7) cell lines and their corresponding selective cytotoxicity (SI) was estimated using normal lung fibroblast (WI-38) cells. Most of the organic selenides exhibited good anticancer activity, and this was more pronounced in HepG2 cells. Interestingly, the naphthoquinone- (5), thiazol- (12), and the azo-based (13) organic selenides demonstrated promising SI (up to 76). Furthermore, the amine 4c, naphthoquinone 5, and azo-based 13 and 15 organic selenides were able to down-regulate the expression of Bcl-2 and up-regulate the expression levels of IL-2, IL-6 and CD40 in HepG2 cells compared to untreated cells. Moreover, most of the synthesized candidates manifested good free radical-scavenging and GPx-like activities comparable to vitamin C and ebselen. The obtained results suggested that some of the presented organoselenium candidates have promising anti-HepG2 and antioxidant activities.

Topics: Antineoplastic Agents; Antioxidants; Biphenyl Compounds; Breast Neoplasms; Carcinoma, Hepatocellular; Cell Line; Cell Proliferation; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Female; Hep G2 Cells; Humans; Liver Neoplasms; MCF-7 Cells; Molecular Structure; Organoselenium Compounds; Picrates; Structure-Activity Relationship

The aim of the study was to synthesize nanoparticles (NPs) with chitosan (CS), and poly (lactic acid) (PLA) as a carrier for the drug piceatannol (PIC). The synthesized nanoparticles form the composite of polymeric-drug nanoparticles (CS/PLA-PIC NPs) by dropping method. The preliminary and stability studies were determined for the polymers drug-loading capacity and encapsulation efficiencies. The in vitro drug release study showed that NPs provided a continuous release of the entrapped PIC. The NPs found to be a good scavenger for DPPH, SOD and NO radicals. MTT and LDH assays revealed higher cytotoxic efficacy of CS/PLA-PIC NPs in HepG2, A549 and MCF7 cells compared to CS-PLA NPs and PIC. Dual staining results showed the early/late-stages of apoptotic and necrotic cells. Furthermore, cells treated with CS/PLA-PIC NPs showed fragmenting DNA and also demonstrated for apoptotic cells percentage by flow cytometry. These results suggested that upon CS/PLA-PIC NPs exposure leads to decrease in cancer cell viability due to apoptosis.

Topics: Apoptosis; Biphenyl Compounds; Breast Neoplasms; Cell Line, Tumor; Chitosan; DNA Fragmentation; Drug Carriers; Drug Liberation; Humans; Liver; Lung Neoplasms; MCF-7 Cells; Nanoparticles; Nitric Oxide; Picrates; Polyesters; Stilbenes; Superoxide Dismutase

Topics: Anti-Infective Agents; Antineoplastic Agents; Antioxidants; Bacteria; Biphenyl Compounds; Breast Neoplasms; Clerodendrum; Fungi; Humans; Microbial Sensitivity Tests; Nanoparticles; Picrates; Spectrum Analysis; Tin Compounds; Tumor Cells, Cultured

Inspired by the impressive biological properties of pyrrolo[2,3- d]pyrimidine units, the objective of this study was to synthesize some new derivatives of heterocyclic compounds with different substituent's using solvent-free microwave irradiation conditions from readily available starting material. The synthesized compounds were screened for their in vitro anti-microbial, anti-oxidant, anti-cancer activities and theoretical molecular docking studies.. Structural elucidation of the synthesized compounds was determined on the basis of various spectroscopic methods. Synthesized compounds have been evaluated for their in vitro antimicrobial activity (MIC) against various microbial strains. After the primary screening, synthesised compounds are further studied for anti-oxidant activity using DPPH assay method, anticancer activity against MCF-7 cell line using MTT assay and molecular docking studies. Moreover, molecular dynamics and simulation was done for best compound using GROMACS.. A series of 2-chloro-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine derivatives 6(a-f), 7(a-c) and 8(a-c) were synthesised using solvent-free microwave irradiation technique. Among all the synthesized compounds, compounds 6e (51.35 μg/mL) and 6f (60.14 µg/mL) showed better activity profile against MCF-7 cell line for breast cancer activity. Compounds 6f and 6d have shown potent antibacterial activity against most of the employed strains, especially against S. pneumoniae, B. cerus and S. aureus. Compound 7a (52.21 µg/mL) showed high potential activity for antioxidant using DPPH assay. Molecular docking study showed good binding of these compounds to the active site of ER- alpha with binding energy ranging from -7.12 kcal/mol to -1.21 kcal/mol. Furthermore, molecular dynamics and simulation was conducted for best pose interacted compound 6e with active site of protein to study its stability and behaviour in nanoscale.. The present research work is intended for facile and efficient green synthesis of various biologically useful potent bio-active molecules from inexpensive and readily available starting substrates under mild reaction condition. These classes of synthesized various heterocyclic compounds holds a great importance to discover newer anti-microbial, anti-oxidant and anti-cancer drugs in future prospects. Further structural modification in these structures will be of interest and may result in compounds having a better therapeutic and biological activity. Hence, this efficient green synthetic protocol and biological results of newly synthesized heterocyclic derivatives are found to be interesting lead molecules for bioactivity in the near future. It could be considered for investigation of their mode of action and for further development.

Topics: Antineoplastic Agents; Antioxidants; Biphenyl Compounds; Breast Neoplasms; Cell Proliferation; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Female; Humans; MCF-7 Cells; Molecular Docking Simulation; Molecular Dynamics Simulation; Picrates; Pyrimidines; Structure-Activity Relationship

Scurrula ferruginea (Jack) Danser is one of the mistletoe species belonging to Loranthaceae family, which grows on the branches of many deciduous trees in tropical countries. This study evaluated the antioxidant activities of S. ferruginea extracts. The cytotoxic activity of the selected extracts, which showed potent antioxidant activities, and high phenolic and flavonoid contents, were investigated in human breast cancer cell line (MDA-MB-231) and non-cancer human skin fibroblast cells (HSF-1184). The activities and characteristics varied depending on the different parts of S. ferruginea, solvent polarity, and concentrations of extracts. The stem methanol extract showed the highest amount of both phenolic (273.51 ± 4.84 mg gallic acid/g extract) and flavonoid contents (163.41 ± 4.62 mg catechin/g extract) and strong DPPH• radical scavenging (IC50 = 27.81 μg/mL) and metal chelation activity (IC50 = 80.20 μg/mL). The stem aqueous extract showed the highest ABTS•+ scavenging ability. The stem methanol and aqueous extracts exhibited dose-dependent cytotoxic activity against MDA-MB-231 cells with IC50 of 19.27 and 50.35 μg/mL, respectively. Furthermore, the extracts inhibited the migration and colony formation of MDA-MB-231 cells in a concentration-dependent manner. Morphological observations revealed hallmark properties of apoptosis in treated cells. The methanol extract induced an increase in ROS generation and mitochondrial depolarization in MDA-MB-231 cells, suggesting its potent apoptotic activity. The present study demonstrated that the S. ferruginea methanol extract mediated MDA-MB-231 cell growth inhibition via induction of apoptosis which was confirmed by Western blot analysis. It may be a potential anticancer agent; however, its in vivo anticancer activity needs to be investigated.

Topics: Antioxidants; Apoptosis; Biphenyl Compounds; Breast Neoplasms; Caspase 3; Caspase 7; Cell Line, Tumor; Cell Movement; Cell Nucleus; Cell Proliferation; Flavonoids; Humans; Iron; Membrane Potential, Mitochondrial; Methanol; Phenols; Picrates; Plant Extracts; Plant Stems; Poly(ADP-ribose) Polymerases; Reactive Oxygen Species; Tracheophyta; Water

Four new chromone derivatives, phomopsichins A-D (

Topics: Acetylcholinesterase; alpha-Glucosidases; Biphenyl Compounds; Breast Neoplasms; Cell Line, Tumor; Chromones; Crystallography, X-Ray; Endophytes; Fermentation; Fungi; Humans; Molecular Structure; Picrates; X-Ray Diffraction; Xanthones

Petroselinum crispum (English parsley) is a common herb of the Apiaceae family that is cultivated throughout the world and is widely used as a seasoning condiment. Studies have shown its potential as a medicinal herb. In this study, P. crispum leaf and stem extracts were evaluated for their antioxidant properties, protection against DNA damage in normal 3T3-L1 cells, and the inhibition of proliferation and migration of the MCF-7 cells.. The dichloromethane extract of P. crispum exhibited the highest phenolic content (42.31 ± 0.50 mg GAE g(-1) ) and ferric reducing ability (0.360 ± 0.009 mmol g(-1) ) of the various extractions performed. The extract showed DPPH radical scavenging activity with an IC50 value of 3310.0 ± 80.5 µg mL(-1) . Mouse fibroblasts (3T3-L1) pre-treated with 400 µg mL(-1) of the extract showed 50.9% protection against H2 O2 -induced DNA damage, suggesting its potential in cancer prevention. The extract (300 µg mL(-1) ) inhibited H2 O2 -induced MCF-7 cell migration by 41% ± 4%. As cell migration is necessary for metastasis of cancer cells, inhibition of migration is an indication of protection against metastasis.. Petroselinum crispum has health-promoting properties with the potential to prevent oxidative stress-related diseases and can be developed into functional food.

Topics: 3T3-L1 Cells; Animals; Antineoplastic Agents, Phytogenic; Antioxidants; Biphenyl Compounds; Breast Neoplasms; Cell Movement; Cell Proliferation; DNA; DNA Damage; Female; Functional Food; Humans; Hydrogen Peroxide; MCF-7 Cells; Mice; Neoplasm Metastasis; Oxidative Stress; Petroselinum; Phenols; Phytotherapy; Picrates; Plant Extracts; Plant Leaves

Pineapple has a delicious taste and good health benefits. Bioactive polysaccharides are important components of pineapple that might contribute to its health benefits. Since little structural information on these polysaccharides is currently available, the aim of this study was to investigate their structural characteristics and bioactivities.. The polysaccharides of pineapple pulp were fractionated into three fractions (PAPs 1-3) by anion exchange chromatography. Their structural characteristics were first identified, including molecular weights and glycosidic linkages. The monosaccharide compositions were revealed as PAP 1 (Ara, Xyl, Man, Glc and Gal), PAP 2 (Rha, Ara, Xyl, Man, Glc and Gal) and PAP 3 (Rha, Ara, Xyl, Man and Gal). Nuclear magnetic resonance (NMR) spectra suggested that PAP 2 had a backbone of → 4)-α-d-Manp-(1 → 2,4)-α-d-Manp-(1 → with branches attached to O-4 of Manp. The NMR data of α-l-Araf-(1→, →3)-α-l-Araf-(1→, →4)-β-d-Galp-(1 → and → 4)-α-d-GalpAMe-(1 → were assigned. PAPs 1 and 2 showed significant antitumor cell proliferation activities against breast carcinoma cell line and strong antioxidant activities.. The above findings indicated that PAPs 1-3 contributed much to the health benefits of pineapple. They could be used as health-beneficial food additives in functional foods.

Topics: Ananas; Antineoplastic Agents; Biphenyl Compounds; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Female; Humans; Magnetic Resonance Spectroscopy; Pancreatitis-Associated Proteins; Phytotherapy; Picrates; Polysaccharides

Rosa rugosa petals are used for production of teas, jams, wines and juices. Despite the wide availability of rose cultivars, comprehensive information on petal chemical composition and healthful properties is still lacking. Therefore, the aim of this study was analysis of cytotoxic, antioxidant and antimicrobial activity and chemical composition of rugosa rose petals.. Petals of R. rugosa were evaluated for their cytotoxic effect against cervical (HeLa) and breast cancer (T47D) cell lines and for antiradical activity (with DPPH•). As a result, significant cytotoxic (up to 100% of dead cells) and antiradical properties (IC₅₀ 1.33-0.08 mg mg⁻¹ DPPH•) were demonstrated. Moreover, notable antimicrobial activity against eight bacterial (i.e. Staphylococcus. epidermidis, S. aureus, Bacillus subtilis, Micrococcus luteus, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus mirabilis) and two yeast strains (Candida. albicans, C. parapsilosis) was shown. Total phenolic, flavonoid, phenolic acid, tannin, carotenoid and polysaccharide content in petals was determined using spectrophotometric methods. Liquid chromatography-electrospray ionization-tandem mass spectrometry was used to thoroughly analyze phenolic acids and flavonoid glycosides in the methanolic extract and fractions obtained after its separation. Five phenolic acids and six flavonoids previously not reported in the plant material were identified.. This is the first such detailed report on chemical composition and biological activity of R. rugosa petals.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Antifungal Agents; Antineoplastic Agents, Phytogenic; Antioxidants; Bacteria; Biphenyl Compounds; Breast Neoplasms; Candida; Female; Flavonoids; Flowers; Glycosides; HeLa Cells; Humans; Neoplasms; Phenols; Phytotherapy; Picrates; Plant Extracts; Rosa; Uterine Cervical Neoplasms

A new chlorogenate oxidovanadium complex (Na[VO(chlorog)(H2O)3].4H2O) was synthesized by using Schlenk methodology in the course of a reaction at inert atmosphere in which deprotonated chlorogenic acid ligand binds to oxidovanadium(IV) in a reaction experiment controlled via EPR technique and based in a species distribution diagram. The compound was characterized by FTIR, EPR, UV-visible and diffuse reflectance spectroscopies and thermogravimetric, differential thermal and elemental analyses. The ligand and the complex were tested for their antioxidant effects on DPPH (1,1-diphenyl-2-picrylhydrazyl radical), ABTS(+) (radical cation of 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt), O2(-), OH and ROO radicals and their cytotoxic activity on different cancer cell lines (SKBR3, T47D and MDAMB231) and primary human mammary epithelial cells. The complex behaved as good antioxidant agent with strongest inhibitory effects on O2(-), OH and ROO radicals and exhibited selective cytotoxicity against SKBR3 cancer cell line. Albumin interaction experiments denoted high affinity toward the complex and its calculated binding constant was indicative of a strong binding to the protein. Based on this study, it is hypothesized that Na[VO(chlorog)(H2O)3].4H2O would be a promising candidate for further evaluation as an antioxidant and anticancer agent.

Topics: Animals; Antineoplastic Agents; Biphenyl Compounds; Breast Neoplasms; Cattle; Cell Line, Tumor; Cell Proliferation; Cell Survival; Coordination Complexes; Drug Stability; Female; Free Radical Scavengers; Free Radicals; Humans; Oxidation-Reduction; Picrates; Protein Binding; Serum Albumin, Bovine; Superoxide Dismutase

To investigate the molecular effects of Nerium oleander leaf distillate on paclitaxel and vincristine resistant (MCF-7/Pac and MCF-7/Vinc) cells and sensitive (MCF-7/S) cell lines.. Nerium oleander (N. oleander) leaf extract was obtained by hydrodistillation method. The toxicological effects of N. oleander distillate, previously suggested as medicinal food supplement, on drug resistant cells were evaluated by XTT tests. MDR modulation potential of the plant material was evaluated by flow cytometry and fluorescent microscopy. Paclitaxel and vincristine were applied to the sublines in combination with N. oleander distillate.. Fractional inhibitory indices show that N. oleander distillate did not increase the antiproliferative effects of anticancer drugs. N. oleander treatment in to MCF-7/Pac and MCF-7/Vinc did not inhibit P-gp activity and MDR1 gene expression level.. As a result it may be suggested that although N. oleander distillate has some medicinal effects as food supplement it may not be suitable as an MDR modulator for drug resistant breast cancer cells.

Topics: Antineoplastic Agents, Phytogenic; ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily B, Member 1; Biphenyl Compounds; Breast Neoplasms; Dietary Supplements; Drug Resistance, Multiple; Female; Flow Cytometry; Gene Expression Regulation, Neoplastic; Humans; MCF-7 Cells; Nerium; Paclitaxel; Picrates; Plant Extracts; Plant Leaves; Polymerase Chain Reaction; Vincristine

Four new ruthenium(II) complexes with N(4)-methyl thiosemicarbazone ligands, (E)-2-(2-chlorobenzylidene)-N-methylhydrazinecarbothioamide (HL(1)) and (E)-N-methyl-2-(2-nitrobenzylidene)hydrazinecarbothioamide (HL(2)), were prepared and fully characterized by various spectro-analytical techniques. The Schiff bases act as bidentate, monobasic chelating ligands with S and N as the donor sites and are preferably found in the thiol form in all the complexes studied. The molecular structure of HL(1) and HL(2) were determined by single crystal X-ray diffraction method. DNA binding of the compounds was investigated by absorption spectroscopy which indicated that the complexes bind to DNA via intercalation. The oxidative cleavage of the complexes with CT-DNA inferred that the effects of cleavage are dose dependent. Antioxidant studies of the ligands and complexes showed the significant antioxidant activity against DPPH radical. In addition, the in vitro cytotoxicity of the ligands and complexes against MCF-7 cell line was assayed which showed higher cytotoxic activity with the lower IC(50) values indicating their efficiency in killing the cancer cells even at low concentrations.

Topics: Animals; Antineoplastic Agents; Antioxidants; Benzaldehydes; Biphenyl Compounds; Breast; Breast Neoplasms; Cattle; Cell Line, Tumor; Cell Survival; Crystallography, X-Ray; DNA; DNA Cleavage; Female; Free Radicals; Humans; Models, Molecular; Picrates; Ruthenium; Thiosemicarbazones

The intent of this study was to purify and characterize a polysaccharide named LA from the fruiting bodies of the edible mushroom Pleurotus abalones.. The 120-kDa polysaccharide was obtained by extraction with boiling water, ethanol precipitation, ion exchange chromatography on Diethylaminoethyl-cellulose and gel filtration on Sephadex G-200.. The LA was composed of glucose, rhamnose, glucuronic acid, xylose, galactose and arabinose in the molar ratio of 26.3:2.7:1:1.4:1.8:1.2. The FITR and 1H-NMR spectrum of LA disclosed that it was a saccharide with an α-configuration. Its 13C-NMR spectrum revealed that its main chain was [→6)-α-D-Gly(1→]n. The LA exhibited antioxidant activities, especially in scavenging 1,1- diphenyl-2-picryl-hydrazyl radicals and hydroxyl radicals. It manifested antiproliferative activity towards breast cancer MCF7 cells with an IC50 of 3.7 µm, and also exerted some antiproliferative activity against HepG2 cells. It manifested a hypoglycemic action on diabetic mice. It inhibited HIV-1 reverse transcriptase with an IC50 of 8.7 × 10(-2) µm.. The polysaccharide from the abalone mushroom.

Topics: Antineoplastic Agents; Antioxidants; Biological Products; Biphenyl Compounds; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Diabetes Mellitus; Female; Fruiting Bodies, Fungal; Hep G2 Cells; HIV Reverse Transcriptase; Humans; Hydroxyl Radical; Hyperglycemia; Hypoglycemic Agents; Inhibitory Concentration 50; Liver Neoplasms; Phytotherapy; Picrates; Pleurotus; Polysaccharides; Reverse Transcriptase Inhibitors

Pomegranate (Punica granatum L.) is known to possess pharmacological activities, such as antioxidant and anticancer. In this study, we evaluated the antioxidant potency of a methanolic pomegranate fruit peel extract (PPE) and the relation with its antiproliferative and apoptotic effects on MCF-7 human breast cancer cells. Total phenolic content and antioxidant activity of PPE were determined using the Folin-Ciocalteau and the 2,2-diphenyl-l-picrylhydrazyl free radical methods, respectively. Phenolic acids present in the extract were characterized by a reverse-phase high-performance liquid chromatography (HPLC) method. Cell proliferation was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction assay. The apoptotic effects were determined by in situ Tdt-mediated dUTP nick end-labeling assay, and Bax/Bcl-2 mRNA expression levels were measured by reverse transcription-polymerase chain reaction. The extraction yield as a percentage of plant material was 37.97% (wt/wt), and total phenolic content was 331.28 mg of gallic acid equivalents/g of extract. According to HPLC analysis, the most abundant phenolic acid detected in the extract was ellagic acid. MCF-7 cell proliferation decreased depending on PPE concentration (25, 50, 100, 200, and 300 μg/mL) and incubation times (24, 48, and 72 hours). After 48 and 72 hours, the apoptotic cell numbers were significantly increased at 100, 200, and 300 μg/mL PPE concentrations. In addition, expression of the pro-apoptotic gene Bax was increased, and that of the anti-apoptotic gene Bcl-2 was decreased after 200 and 300 μg/mL PPE treatment for 48 and 72 hours. Because PPE reduced cell proliferation and induced apoptosis on MCF-7 cancer cells, we believe that PPE has important antioxidant and apoptotic effects.

Topics: Antioxidants; Apoptosis; bcl-2-Associated X Protein; Biphenyl Compounds; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; Ellagic Acid; Female; Fruit; Gene Expression Regulation; Humans; Hydroxybenzoates; Lythraceae; Molybdenum; Phenols; Picrates; Plant Extracts; RNA, Messenger; Tungsten Compounds

In our work, we evaluate the potential antioxidant, antimalarial activity and also activity against human breast cancer cells (MCF7) of Argan fruit extracts using in vitro models to validate the traditional use of this plant. Its chemical composition was also studied to begin the understanding of its activities, waiting to find the structure-activity relationship.. Polyphenols (89.4-218.5 eqGallic acid (mg/g dry)), tannins (39.3-214.0 eqCatechin (mg/g dry)), flavonoids (3.4-11.1 eqQuercetin (mg/g dry)) and anthocyanins (0.74-10.92 eqCyanindin (mug/g dry)) were quantified. A good (ethyl acetate and decoction) and moderate (petroleum ether) antioxidant activity were obtained for DPPH (IC(50) 32.3-600.8 microg/ml) and ABTS (IC(50) 11.9-988.8 microg/ml) assays. In addition, we found a good antimalarial activity (IC(50) 35 to >100 microg/ml) and human breast cancer cells activity (IC(50) 42 to >100 microg/ml).. The ethyl acetate extract and the decoction show interesting antimalarial and antioxidant activities. The results indicate a good correlations between anthocyanins quantitiy and the potential antioxidant (R(2)=0.9867) and also to antimalarial activity (R(2)=0.8175).

Topics: Antimalarials; Antineoplastic Agents, Phytogenic; Antioxidants; Benzothiazoles; Biphenyl Compounds; Breast Neoplasms; Cell Line, Tumor; Female; Flavonoids; Fruit; Humans; Inhibitory Concentration 50; Phenols; Phytotherapy; Picrates; Plant Extracts; Plasmodium falciparum; Sapotaceae; Sulfonic Acids; Tannins

Bioconversion of the isoflavonoid genistein to 2'- hydroxygenistein (2'-HG) was performed using isoflavone 2'-hydroxylase (CYP81E1) heterologously expressed in yeast. A monohydroxylated product was analyzed by liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) and NMR spectrometry and was identified as 2'-HG. An initial bioconversion rate of 6% was increased up to 14% under optimized conditions. After recovery, the biological activity of 2'-HG was evaluated. Bioconverted 2'-HG showed higher antioxidant activity against 1,1- diphenyl-2-picryl hydrazine (DPPH) and 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radicals than did genistein. Furthermore, 2'-HG exhibited greater antiproliferative effects in MCF-7 human breast cancer cells than did genistein. These results suggest that 2'- hydroxylation of genistein enhanced its antioxidant activity and cell cytotoxicity in MCF-7 human breast cancer cells.

Topics: Anticarcinogenic Agents; Antioxidants; Benzothiazoles; Biphenyl Compounds; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Cell Survival; Chromatography, Liquid; Cytochrome P-450 Enzyme System; Dose-Response Relationship, Drug; Female; Genistein; Humans; Hydroxylation; Magnetic Resonance Spectroscopy; Picrates; Spectrometry, Mass, Electrospray Ionization; Sulfonic Acids

Quercetin (QUE; 3,5,7,3',4'-tetrahydroxyflavone) has been shown to possess several beneficial biological activities including antitumor, anti-inflammation and antioxidant properties; however, the effects of QUE in preventing invasion by breast carcinoma cells are still undefined. Increases in the protein, messenger RNA and enzyme activity levels of matrix metalloproteinase (MMP)-9 were observed in 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated MCF-7 cells, and these were blocked by QUE, but not by quercitrin or rutin. A translocation of protein kinase C (PKC)delta from the cytosol to the membrane followed by activation of extracellular signal-regulated kinase (ERK) and c-Jun/activator protein-1 (AP-1) by TPA was demonstrated, and TPA-induced MMP-9 activation and migration were inhibited by the pan PKC inhibitor, GF109203X, the specific PKCdelta inhibitor, rottlerin, an ERK inhibitor (PD98059) and an AP-1 inhibitor (curcumin). Application of QUE significantly suppressed TPA-induced activation of the PKCdelta/ERK/AP-1-signaling cascade. To elucidate the importance of hydroxyl (OH) substitutions to QUE's inhibition of tumor migration, several structurally related flavones of QUE including 3',4'-diOH, 3',4'-diOCH(3), 3,5,7-triOH, 3,4',4'-triOH, 3,3',4'-triOCH(3), luteolin and fisetin were used. Results suggested that OH groups at both C3' and C4' play central roles in QUE's inhibition of TPA-induced MMP-9 activation and migration, and an additional OH at C3, C5 or C7 may increase the inhibitory potency of the 3',4'-diOH flavone against TPA-induced MMP-9 activity and migration. The antitumor invasion and migration effects of breast carcinoma cells induced by QUE with the structure-activity relationship analysis were identified.

Topics: Biphenyl Compounds; Breast Neoplasms; Carcinogens; Cell Movement; Enzyme Activation; Gene Expression Regulation, Neoplastic; Humans; Hydrazines; Hydroxyl Radical; Matrix Metalloproteinase 9; Matrix Metalloproteinase Inhibitors; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Neoplasm Invasiveness; Picrates; Protein Kinase C-delta; Quercetin; Tetradecanoylphorbol Acetate; Transcription Factor AP-1; Transcription, Genetic

The aromatic herb Melissa officinalis L. can be used as an easily accessible source of natural antioxidants and as a possible food supplement and as a phytochemical. Radical scavenging, antibacterial, and antiproliferative activities of petroleum ether, chloroform, ethyl acetate, n-butanol, and water extracts of M. officinalis L. extracts were investigated. The results of antioxidative activity, obtained by electron spin resonance spectroscopy, confirmed that investigated extracts suppressed the formation of 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydroxyl, and lipid peroxyl radicals in all investigated systems in a dose-dependent manner. The maximum DPPH and hydroxyl radical scavenging activities (SA(DPPH) = SA(OH) = 100%) were achieved in the presence of n-butanol extract at concentrations of 0.4 mg/mL and 0.5 mg/mL, respectively. The highest lipid peroxyl scavenging activity (93.20%) was observed at a higher concentration (5 mg/mL) of n-butanol extract in the lipid peroxidation system. The most effective antibacterial activities were expressed by petroleum ether and ethyl acetate extracts on Sarcina lutea. Chloroform extract showed the strongest antiproliferative effect with 50% inhibitory concentration values of 0.09 mg/mL and 0.10 mg/mL for HeLa and MCF-7 cell lines, respectively. The present study demonstrated the high phenolic content and radical scavenging, antibacterial, and antiproliferative activities of extracts of M. officinalis L. originating from Serbia.

Topics: Anti-Bacterial Agents; Antineoplastic Agents, Phytogenic; Antioxidants; Bacteria; Biphenyl Compounds; Breast Neoplasms; Cell Division; Cell Line, Tumor; Electron Spin Resonance Spectroscopy; Free Radical Scavengers; HeLa Cells; Humans; Hydroxyl Radical; Lipid Peroxidation; Melissa; Peroxides; Phenols; Picrates; Plant Extracts

The biological activity of methanolic and aqueous extracts from dehydrated hypocotyls of Lepidium meyenii (Brassicaceae, vernacular name "maca"), was studied on rat hepatocytes and human breast cancer MCF-7 cells. The extracts did not exhibit cytotoxicity in hepatocyte primary cultures up to 10 mg/ml as measured by the MTT viability test, and lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) leakage. Moreover, after 72 h, extracts inhibited LDH and AST leakage from the hepatocytes. When hepatocytes were intoxicated by t-butyl hydroperoxide, neither extract prevented oxidative damage. Both extracts showed weak antioxidant activity in the DPPH radical scavenging test with IC(50) values of 3.46 +/- 0.16 and 0.71 +/- 0.10 mg/ml, for aqueous and methanolic extracts, respectively. Thus, the observed effect on spontaneous enzyme leakage is probably mediated through mechanisms other than antioxidant activity. Both methanolic and aqueous extracts have shown estrogenic activity comparable with that of silymarin in MCF-7 cell line. Maca estrogenicity was exhibited in the range from 100 to 200 mug of extract per ml. The findings in the present study show that maca does not display in vitro hepatotoxicity. In contrast, a slight cytoprotective effect, probably not mediated by antioxidant capacity, was noted. Maca extracts exhibited estrogenic activity comparably to the effect of silymarin in MCF-7 cells.

Topics: Animals; Biphenyl Compounds; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Cells, Cultured; Drug Evaluation, Preclinical; Estrogens; Fatty Acids; Hepatocytes; Humans; Hydrazines; Lepidium; Male; Picrates; Plant Extracts; Rats; Rats, Wistar; Steroids

A new lignan, actaealactone (1), and a new phenylpropanoid ester derivative, cimicifugic acid G (2), together with 15 known polyphenols, protocatechuic acid, protocatechualdehyde, p-coumaric acid, caffeic acid, methyl caffeate, ferulic acid, ferulate-1-methyl ester, isoferulic acid, 1-isoferuloyl-beta-d-glucopyranoside, fukinolic acid, and cimicifugic acids A, B, and D-F, were isolated from an extract of the rhizomes and roots of black cohosh (Actaea racemosa). The structures of the new compounds were determined on the basis of NMR spectroscopic analysis. Compounds 1 and 2 displayed antioxidant activity in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free-radical assay with IC(50) values of 26 and 37 microM, respectively. Other antioxidants identified from A. racemosa include cimicifugic acid A (3), cimicifugic acid B (4), and fukinolic acid (5). Compounds 1 and 2 also exhibited a small stimulating effect on the growth of MCF-7 breast cancer cell proliferation 1.24-fold (14 microM) and 1.14-fold (10 microM), respectively, compared to untreated cells.

Topics: Biphenyl Compounds; Breast Neoplasms; Caffeic Acids; Cimicifuga; Female; Flavonoids; Free Radical Scavengers; Humans; Lignans; Molecular Structure; Phenols; Phenylacetates; Picrates; Plant Roots; Plants, Medicinal; Polyphenols; Rhizome; Tumor Cells, Cultured

Dou-chi, a traditional soybean food fermented with Aspergillus sp., is usually used as a seasoning in Chinese food, and has also been used as a folk medicine in China and Taiwan. As 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavengers, four phenol compounds, one isoflavanone, eight isoflavones and one 4-pyrone have been isolated from dou-chi. Among these fourteen compounds, 3'-hydroxydaidzein, dihydrodaidzein and a 4-pyrone compound have not yet been isolated from soybean miso. The structure of the novel 4-pyrone compound, 3-((E)-2-carboxyethenyl)-5-(4-hydroxyphenyl)-4-pyrone-2-carboxylic acid was elucidated by using the same compound as that obtained from the biotransformation of daidzein. 3'-Hydroxydaidzein showed as high DPPH radical-scavenging activity as that of alpha-tocopherol, and 6-hydroxydaidzein had mushroom tyrosinase inhibitory activity with an IC(50) value of 10 muM. The order of estrogenic activity is as follows: genistein > daidzein >> 3'-hydroxydaidzein > 8-hydroxygenistein, using a green fluorescent protein expression system. Furthermore, the contents of isoflavones in the fermentation process of dou-chi were measured.

Topics: Antimutagenic Agents; Biphenyl Compounds; Breast Neoplasms; Cell Line, Tumor; Fermentation; Free Radical Scavengers; Humans; Isoflavones; Lipoxygenase; Molecular Structure; Monophenol Monooxygenase; Phytoestrogens; Picrates; Soy Foods

Solanum nigrum L. (SNL) has been traditionally used as a herbal plant, whose fruit is believed to have anti-tumor properties, although the mechanism for the activity remains to be elucidated. In this study, we prepared an ethanol extract from ripe fruits of SNL and investigated the mechanism involved in its growth-inhibitory effect on MCF-7 human breast cancer cells. Results from proliferation assay using tritium uptake showed that the proliferative capacity of MCF-7 cells was strongly suppressed in the presence of SNL ethanol extract. This was further confirmed through MTT assay and trypan blue exclusion experiments, which showed a very close correlation between the SNL extract concentration and the surviving cell numbers. The SNL extract-mediated suppression of cell growth was verified to be apoptotic, based on the appearance of DNA laddering, increase in DNA fragmentation, and low fluorescence intensity in nuclei after propidium iodide staining of the cells. Furthermore, the SNL extract was revealed to be a potential scavenger of hydroxyl radicals and DPPH radicals rather than superoxide anions. Collectively, our findings suggest that SNL fruit extract could be used as an anti-oxidant and cancer chemo-preventive material.

Topics: Antioxidants; Apoptosis; Biphenyl Compounds; Breast Neoplasms; Cell Survival; DNA Fragmentation; DNA, Neoplasm; Female; Flow Cytometry; Free Radicals; Humans; Hydroxyl Radical; Phenols; Picrates; Solanum nigrum; Superoxides; Tumor Cells, Cultured

The roots/rhizomes of Cimicifuga racemosa L. (Nutt.) (black cohosh) have traditionally been used to treat menopausal symptoms through an unknown mechanism of action. In an effort to determine if black cohosh had additional health benefits, methanol extracts were investigated for their potential to scavenge reactive oxygen species and to protect against menadione-induced DNA damage. These extracts effectively scavenged 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radicals. In addition, the extracts showed dose-dependent decreases in DNA single-strand breaks and oxidized bases induced by the quinone menadione using the comet (single-cell gel electrophoresis assay) and fragment length associated repair enzyme assays, respectively. Bioassay-directed fractionation of the methanolic extracts using the DPPH assay as a monitor led to the isolation of nine antioxidant active compounds: caffeic acid (1), methyl caffeate (2), ferulic acid (3), isoferulic acid (4), fukinolic acid (5), cimicifugic acid A (6), cimicifugic acid B (7), cimicifugic acid F (8), cimiracemate A (9), and cimiracemate B (10). Six of these antioxidants were found to reduce menadione-induced DNA damage in cultured S30 breast cancer cells with the following order of potency: methyl caffeate (2) > caffeic acid (1) > ferulic acid (3) > cimiracemate A (9) > cimiracemate B (10) > fukinolic acid (5). These data suggest that black cohosh can protect against cellular DNA damage caused by reactive oxygen species by acting as antioxidants.

Topics: Antioxidants; Biphenyl Compounds; Breast Neoplasms; Cimicifuga; DNA Damage; Estrogen Receptor alpha; Free Radical Scavengers; Gene Expression; Humans; Methanol; Picrates; Plant Extracts; Reactive Oxygen Species; Receptors, Estrogen; Transfection; Tumor Cells, Cultured; Vitamin K 3