Adenocarcinoma Cell Line MCF-7 Research Articles

Antiproliferative potential of Plinia edulis leaves

Plinia edulis, popularly known as ‘cambucá’, is used in Brazilian folk medicine to treat several conditions. The aim of this study was to evaluate the mutagenicity and cytotoxicity of cambucá leaf extract, as well as its antioxidant activity. The ‘Ames’ test and Orac assay were used to evaluate the mutagenicity and antioxidant activity, respectively, and the phytochemical analysis of the ethanol leaf extract (LE) was performed by chromatographic and spectrometric methods. The in vitro cytotoxicity was tested on CHO (Chinese Hamster Ovary) cells and on nine human tumor cell lines. Phytochemical analysis of LE has revealed the presence of triterpenes and flavonoids. The LE did not show mutagenicity at the concentration of 20 mg plate-1 and exhibited high antioxidant activity, with Orac value of 3948 µmol TE g-1. The LE and its fractions (ethyl acetate; methanol) showed antiproliferative activity against cancer cell lines and proliferative activity in normal cells. The ethyl acetate fraction was the most active extract, presenting antiproliferative activity against strains of breast cancer, prostate cancer, colon cancer, lung cancer, melanoma and leukemia (GI50 0.01-8.57 µg mL-1), being more effective than the reference drug (doxorubicin) against human breast adenocarcinoma MCF-7 cell line. These results suggest P. edulis as a potential adjuvant in cancer therapy and chemoprevention.

Synthesis, cytotoxicity and antioxidant activity of new conjugates of N-acetyl-d-glucosamine with α-aminophosphonates

A series of the first conjugates of N-acetyl-d-glucosamine with α-aminophosphonates was synthesized using the Kabachnik-Fields reaction, the Pudovik reaction, a copper(I)-catalyzed azide-alkyne cycloaddition reaction (CuAAC) and evaluated for the in vitro cytotoxicity against human cancer cell lines M − HeLa, HuTu-80, A549, PANC-1, MCF-7, T98G and normal lung fibroblast cells WI-38. The tested conjugates, with exception of compound 21b, considered as a lead compound, were either inactive against the used cancer cells or showed moderate cytotoxicity in the range of IC50 values 33−80 μM. The lead compound 21b, being non cytotoxic against normal human cells WI-38 (IC50 = 90 μM), demonstrated good activity (IC50 = 17 μM) against breast adenocarcinoma cells (MCF-7) which to be 1.5 times higher than the activity of the used reference anticancer drug tamoxifen (IC50 = 25.0 μM). A flexible receptor molecular docking simulation showed that the cytotoxicity of the synthesized conjugates of N-acetyl-d-glucosamine with α-aminophosphonates against breast adenocarcinoma MCF-7 cell line is due to their ability to inhibit EGFR kinase domain. In addition, it was found that conjugates 22a and 22b demonstrated antioxidant activity that was not typical for α-aminophosphonates.

Differences in nonoxidative sulfur metabolism between normal human breast MCF-12A and adenocarcinoma MCF-7 cell lines

Recent studies have revealed the role of endogenous hydrogen sulfide (H2S) in the development of breast cancer. The capacity of cells to generate H2S and the activity and expression of the main enzymes (cystathionine beta synthase; CBS, cystathionase γ-lyase; CGL, 3-mercaptopyruvate sulfurtransferase; MPST and thiosulfate sulfurtransferase; TST) involved in H2S metabolism were analyzed using an in vitro model of a non-tumourigenic breast cell line (MCF-12A) and a human breast adenocarcinoma cell line (MCF-7). In both cell lines, MPST, CGL, and TST expression was confirmed at the mRNA (RT-PCR) and the protein (Western Blot) level, while CBS expression was detected only in MCF-7 cells. Elevated levels of GSH, sulfane sulfur and increased CBS and TST activity were presented in the MCF-7 compared to the MCF-12A cells. It appears that cysteine might be mainly a substrate for GSH synthesis in breast adenocarcinoma. Increased capacity of the cells to generate H2S was shown for MCF-12A compared to MCF-7 cell line. Results suggest an important function of CBS in H2S metabolism in breast adenocarcinoma. The presented work may contribute to further research on new therapeutic possibilities for breast cancer - one of the most frequently diagnosed types of cancer among women.

Comparative analysis of oncolytic potential of vesicular stomatitis virus serotypes Indiana and New Jersey in cancer cell lines

Aim. Compare the lytic efficiency and the kinetics of accumulation of vesicular stomatitis virus serotypes Indiana (VSV-IND) and New Jersey (VSV-NJ) on cell lines of mouse melanoma B16F10, human hepatocellular carcinoma HepG2 and human mammary adenocarcinoma MCF7.Materials and methods. The viability of mouse melanoma B16F10, human hepatocellular carcinoma HepG2 and human mammary adenocarcinoma MCF7 cell lines infected with VSV-IND and VSV-NJ viruses at different multiplicity of infection (10 MOI; 1 MOI; 0.1 MOI) was assessed after 24, 48 and 72 hours, and the half maximal inhibitory concentration (IC50) values were measured using the methyl tetrazolium test. The relationship with virus accumulation in cell culture was determined using reverse transcription – quantitative polymerase chain reaction; 50% tissue culture infectious dose (TCID50) of VSV-IND and VSV-NJ for B16F10, HepG2, MCF7 were calculated using the Reed-Muench method.Results. The most susceptible cell line for both viruses was B16F10: cell viability 72 hours after infection at 10 MOI was only 10.4% and 5.7% for VSV-IND and VSV-NJ, respectively. HepG2 cell viability at 72 hours post-infection at 10 MOI was 10.8% and 9.8% for VSV-IND and VSV-NJ, and for MCF7 adenocarcinoma it was 46.6% and 36.2%, respectively. Moreover, only in the B16F10 culture was a positive statistically significant correlation of medium strength established between the inhibition of cell viability and the accumulation of viral RNA: for VSV-IND r = 0.601 (p < 0.05); for VSV-NJ r = 0.668 (p < 0.05). HepG2 and MCF7 showed no significant correlation.Conclusion. The research results indicate the potential of using oncolytic viruses of the VSV-IND and VSV-NJ as a platform for the development of new recombinant viruses for virotherapy of solid tumors in combination with other types of treatment.

Phenolic Compounds from Sour Cherry Pomace: Microencapsulation, in Vitro Digestion, and Cell Growth Activities.

The objective of this work was the valorisation of sour cherry (Prunus cerasus L.) pomace as a source of biologically active compounds. To formulate microcapsules, polyphenolic compounds were extracted and encapsulated with maltodextrin as wall material, by freeze-drying. An in vitro digestion study was carried out on obtained encapsulates but also on sour cherry pomace extract and sour cherry pomace freeze-dried powder. The results indicated that encapsulation, as well as freeze-drying, provided a good protective effect on bioactive compounds during digestion. Furthermore, the potential antiproliferative and cytotoxic activities of encapsulates and sour cherry pomace extract were evaluated using breast adenocarcinoma MCF7 cell lines, colon adenocarcinoma HT-29 cell lines, and noncancer cell line. Encapsulates and sour cherry pomace extract showed variable anti-proliferative activity towards all cell lines. Obtained results showed that encapsulation of sour cherry pomace could be useful for improving the stability of polyphenolic compounds in the gastrointestinal tract. The results highlight the bioactive potential of sour cherry pomace as a nutraceutical resource and the protective effects of microencapsulation on the digestion of bioactive compounds.

3-(1,2,3-Triazol-4-yl)-β-Carbolines and 3-(1H-Tetrazol-5-yl)-β-Carbolines: Synthesis and Evaluation as Anticancer Agents.

Herein, the synthesis and anticancer activity evaluation of a series of novel β-carbolines is reported. The reactivity of nitrosoalkenes towards indole was explored for the synthesis of novel tryptophan analogs where the carboxylic acid was replaced by a triazole moiety. This tryptamine was used in the synthesis of 3-(1,2,3-triazol-4-yl)-β-carbolines via Pictet-Spengler condensation followed by an oxidative step. A library of compounds, including the novel 3-(1,2,3-triazol-4-yl)-β-carbolines as well as methyl β-carboline-3-carboxylate and 3-tetrazolyl-β-carboline derivatives, was evaluated for their antiproliferative activity against colorectal cancer cell lines. The 3-(1H-tetrazol-5-yl)-β-carbolines stood out as the most active compounds, with values of half-maximal inhibitory concentration (IC50) ranging from 3.3 µM to 9.6 µM against colorectal adenocarcinoma HCT116 and HT29 cell lines. The results also revealed a mechanism of action independent of the p53 pathway. Further studies with the 3-tetrazolyl-β-carboline derivative, which showed high selectivity for cancer cells, revealed IC50 values below 8 μM against pancreatic adenocarcinoma PANC-1, melanoma A375, hepatocarcinoma HEPG2, and breast adenocarcinoma MCF-7 cell lines. Collectively, this work discloses the 3-tetrazolyl-β-carboline derivative as a promising anticancer agent worthy of being further explored in future works.

ADAPTOR PROTEIN Ruk/CIN85 PARTICIPATES IN THE METABOLIC CONTROL OF HUMAN BREAST ADENOCARCINOMA MCF-7 CELLS

Aim. To determine the role of Ruk/CIN85 in the control of breast adenocarcinoma cells metabolism, we performed systemic analysis of the activity levels/content of key enzymes/components of glycolysis and oxidative phosphorylation using as a model the weakly invasive human breast adenocarcinoma MCF-7 cell line (Mock); and its sublines with stable overexpression (G4 subline) and reverse down-regulation (G4vir subline) of the adaptor protein. Materials and methods. MCF-7 cells were cultured in the complete DMEM medium under standard conditions. Enzymes activity, content of metabolites and protein in cell extracts and the conditioned cell culture medium were estimated by spectrophotometric and fluorometric assays. Results. First of all, biochemical indexes of aerobic glycolysis, activity levels of some key glycolytic enzymes and metabolites were evaluated. A significant increase in the activity of these enzymes, aldolase A (ALDOA) and lactate dehydrogenase A (LDHA), was found in G4 cells compared to Mock by 1.3 and 1.6 times, respectively. In addition, in the conditioned medium of G4 cells, an increase in lactate content by 1.5 times compared with the control was found, which corresponded to a change in LDHA activity. Knockdown of Ruk/CIN85 expression level in G4 subline resulted in a significant decrease of these parameters compared to G4 cells, ALDOA – 4 times, LDHA - 1.4 times, and lactate production - 2.5 times. It should be noted that in G4vir cells, LDHA activity returned to level of control cells, while ALDOA activity and lactate content additionally decreased by 3 times and 1.6 times, respectively. Therefore, the observed changes in the intensity of glycolysis in MCF-7 sublines positively correlate with the expression level of adaptor protein studied. To assess the metabolic status of mitochondria, the level of activity of the Krebs cycle enzyme, NAD-dependent malate dehydrogenase (MDH2), the catalyst of last stage of the cycle, was determined. A 2-fold decrease in MDH2 activity was found in the MCF-7 G4 subline relative to control Mock cells, as well as an increase in this index by 2.4 times in G4vir cells to control values. Unlike glycolysis, we observed the opposite pattern with respect to the intensity of Krebs cycle reactions depending on the expression level of Ruk/CIN85. Conclusions. Use of limited proteolysis technique as the source of additional information for computer modeling allowed us to propose an improved model of 3D-structure of fibrinogen αC-regions. This model takes into account the behavior of αC-regions in the physiological condition and contributes to the general knowledge about fibrinogen structure.

Synthesis of Gold Nanoparticles Using Centella Asiatica Extract and its In Vitro Cytotoxic Activity Against Human Breast Adenocarcinoma MCF-7 and Normal Vero Cell Line

In the past few decades, the gold nanoparticles (AuNPs) have attained much attention among all metal nanoparticles and it is greatly contributed for cancer photo-diagnostics, photo-thermal therapy, bio-labelling, drug delivery etc. In the present investigation, AuNPs were green synthesized using Centella asiatica leaf aqueous extract. The physicochemical properties of synthesized AuNPs were characterized using UV–visible and Transmission Electron Microscopy (TEM) analysis. Further, in vitro anticancer efficacy of biosynthesized AuNPs were assessed against human breast adenocarcinoma (MCF-7) and normal African green monkey kidney Vero cell line. Bio approach synthesized gold nanoparticles were highly stable, monodisperse particles in the size ranging

Cytotoxicity and Anticancer activity of Aqueous Leaf Extract of Solanum torvumon Normal Vero and Human Breast Adenocarcinoma MCF-7 Cell Line

Naturalherbalproducts areformulatedwitha combinationofphytoconstituentsfrom plants which play a pivotalrole becauseof their diverse medicinal properties.Limited plants have been screened for their complete biological and pharmacological nature.In the present research workan attempt wasmade to infer the medicinal value of aqueousextract of Solanumtorvum (S.torvum)leaves. Phytochemical analysis of theaqueous extracts of S.torvumleaf in the present study ascertain the presence of flavonoids, phenols, saponins, alkaloids, coumarins, sterols, proteins and reducing sugars.Further, the potentiality of aqueous extract ofS.torvumleaveswas assessedfor its cytotoxic effecton Normal Verocell lineand anticancer activityonHumanbreast adenocarcinoma cell lineby 3-(4,5dimethylthiazole-2-yl)-2,5-diphenyl tetrazoliumbromide assay.A 24-hour incubationcell proliferation studyreducedthe cell viability of MCF-7 breast cancer cell lines.In vitro studieson cytotoxicity analysis on Vero cell line revealed thattheaqueous leaf extract of S.torvumhasno toxicityand further it was foundtobeeffectiveinthepreventionofcellproliferation by MCF-7celllines.©2022iGlobal Research and PublishingFoundation. All rights reserved.

Cytotoxic Fractions from Hechtia glomerata Extracts and p-Coumaric Acid as MAPK Inhibitors.

Preliminary bioassay-guided fractionation was performed to identify cytotoxic compounds from Hechtia glomerata, a plant that is used in Mexican ethnomedicine. Organic and aqueous extracts were prepared from H. glomerata’s leaves and evaluated against two cancer cell lines. The CHCl3/MeOH (1:1) active extract was fractionated, and the resulting fractions were assayed against prostate adenocarcinoma PC3 and breast adenocarcinoma MCF7 cell lines. Active fraction 4 was further analyzed by high-performance liquid chromatography–quadrupole time-of-flight–mass spectrometry analysis to identify its active constituents. Among the compounds that were responsible for the cytotoxic effects of this fraction were flavonoids, phenolic acids, and aromatic compounds, of which p-coumaric acid (p-CA) and its derivatives were abundant. To understand the mechanisms that underlie p-CA cytotoxicity, a microarray assay was performed on PC3 cells that were treated or not with this compound. The results showed that mitogen-activated protein kinases (MAPKs) that regulate many cancer-related pathways were targeted by p-CA, which could be related to the reported effects of reactive oxygen species (ROS). A molecular docking study of p-CA showed that this phenolic acid targeted these protein active sites (MAPK8 and Serine/Threonine protein kinase 3) at the same binding site as their inhibitors. Thus, we hypothesize that p-CA produces ROS, directly affects the MAPK signaling pathway, and consequently causes apoptosis, among other effects. Additionally, p-CA could be used as a platform for the design of new MAPK inhibitors and re-sensitizing agents for resistant cancers.

Methoxy and bromo scans on N-(5-methoxyphenyl) methoxybenzenesulphonamides reveal potent cytotoxic compounds, especially against the human breast adenocarcinoma MCF7 cell line

Thirty seven N-(5-methoxyphenyl)-4-methoxybenzenesulphonamide with methoxy or/and bromo substitutions (series 1-4) and with different substituents on the sulphonamide nitrogen have been synthesised. 21 showed sub-micromolar cytotoxicity against HeLa and HT-29 human tumour cell lines, and were particularly effective against MCF7. The most potent series has 2,5-dimethoxyanilines, especially the 4-brominated compounds 23–25. The active compounds inhibit microtubular protein polymerisation at micromolar concentrations, thus pointing at tubulin as the target. Co-treatment with the MDR inhibitor verapamil suggests that they are not MDR substrates. Compound 25 showed nanomolar antiproliferative potency. It severely disrupts the microtubule network in cells and arrests cells at the G2/M cell-cycle phase, thus confirming tubulin targeting. 25 triggered apoptotic cell death, and induced autophagy. Docking studies suggest binding in a distinct way to the colchicine site. These compounds are promising new antitumor agents acting on tubulin.

New cyanopyridine-based scaffold as PIM-1 inhibitors and apoptotic inducers: Synthesis and SARs study

Two novel series of 6-(4-benzamido-/4-phthalimido)-3-cyanopyridine derivatives were designed and synthesized as inhibitors of PIM-1 kinase. Based on cytotoxicity results via MTT assay against prostate carcinoma PC3, human hepatocellular carcinoma HepG2 and breast adenocarcinoma MCF-7 cell lines, the most potent cytotoxic cyanopyridine hits, 6, 7, 8, 12 and 13 were 1.5–3.3 times more inhibitor of cell proliferation than the reference standard, 5-FU. Selectivity profile of the latter compounds on normal human cells (WI-38), was executed, indicating that they are highly selective (IC50 > 145 μM) in their cytotoxic effect. The promising compounds were further evaluated as PIM-1 kinase inhibitors. These compounds elicited remarkable inhibition of PIM-1 kinase (76.43–53.33%). Extensive studies on apoptosis were conducted for these compounds; they enhanced caspase-3 and boosted the Bax/Bcl-2 ratio 27-folds in comparison to the control. Molecular docking study of the most potent compound, 13 in PIM-1 kinase active site was consistent with the in vitro activity. Finally, prediction of chemo-informatic properties released compound 13 as the most promising ligand.

New Cytotoxic Cerebrosides from the Red Sea Cucumber Holothuria spinifera Supported by In-Silico Studies.

Bioactivity-guided fractionation of a methanolic extract of the Red Sea cucumber Holothuria spinifera and LC-HRESIMS-assisted dereplication resulted in the isolation of four compounds, three new cerebrosides, spiniferosides A (1), B (2), and C (3), and cholesterol sulfate (4). The chemical structures of the isolated compounds were established on the basis of their 1D NMR and HRMS spectral data. Metabolic profiling of the H. spinifera extract indicated the presence of diverse secondary metabolites, mostly hydroxy fatty acids, diterpenes, triterpenes, and cerebrosides. The isolated compounds were tested for their in vitro cytotoxicities against the breast adenocarcinoma MCF-7 cell line. Compounds 1, 2, 3, and 4 displayed promising cytotoxic activities against MCF-7 cells, with IC50 values of 13.83, 8.13, 8.27, and 35.56 µM, respectively, compared to that of the standard drug doxorubicin (IC50 8.64 µM). Additionally, docking studies were performed for compounds 1, 2, 3, and 4 to elucidate their binding interactions with the active site of the SET protein, an inhibitor of protein phosphatase 2A (PP2A), which could explain their cytotoxic activity. This study highlights the important role of these metabolites in the defense mechanism of the sea cucumber against fouling organisms and the potential uses of these active molecules in the design of new anticancer agents.

Apoptosis-mediated antiproliferation of A549 lung cancer cells mediated by Eugenia aquea leaf compound 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone and its molecular interaction with caspase receptor in molecular docking simulation.

In a previous study, 2′,4′-dihydroxy-6′-methoxy-3′,5′-dimethylchalcone (ChalcEA) isolated from the leaves of Eugenia aquea was reported to inhibit proliferation of the breast adenocarcinoma MCF7 cell line and to promote apoptosis via activation of poly(adenosine diphosphate-ribose) polymerase protein. The present study aimed to evaluate the inhibitory effect of ChalcEA on the proliferation of A549 lung cancer cells using a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxylmethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay, and to examine the ability of ChalcEA to induce apoptosis through activation of the caspase cascade signaling pathway in a western blotting assay. The results revealed that ChalcEA inhibited proliferation of the A549 lung cancer cell lines in a time- and dose-dependent manner with IC50 values of 25.36 and 19.60 µM for 24 and 48 h treatments, respectively. Western blot analysis indicated that ChalcEA exerted its anti-proliferative effects by promoting apoptosis via the activation of caspase-9 and caspase-3. Based on in silico results, ChalcEA with the binding energy of −6.53 kcal/mol could compete better than 4-methyl benzenesulfonamide (−6.43 kcal/mol) as an inhibitor of caspase-3 (PDB: 2XYG). ChalcEA has potential since it has three hydrophobic features. These results provided a basis for further study of ChalcEA as an active compound for anticancer therapeutics.

Design, Synthesis, and Evaluation of Novel 2-Methoxyestradiol Derivatives as Apoptotic Inducers Through an Intrinsic Apoptosis Pathway.

In order to discover novel derivatives in the anti-tumor field, reported anti-tumor pharmacophores (uridine, uracil, and thymine) were combined with 2-methoxyestradiol, which has been characterized as having excellent biological properties in terms of anti-tumor activity. Thus, 20 hybrids were synthesized through etherification at the 17β-OH or 3-phenolic hydroxyl group of 2-methoxyestradiol, and evaluated for their biological activities against the human breast adenocarcinoma MCF-7 cell lines, human breast cancer MDA-MB-231 cell lines, and the normal human liver L-O2 cell lines. As a result, all the uridine derivatives and single-access derivatives of uracil/thymine possessed good anti-proliferative activity against tested tumor cells (half maximal inhibitory concentration values from 3.89 to 19.32 µM), while only one dual-access derivative (21b) of thymine possessed good anti-proliferative activity (half maximal inhibitory concentration ≈ 25 µM). Among them, the uridine derivative 11 and the single-access derivative of uracil 12a possessed good anti-proliferative selectivity against tested tumor cells. Furthermore, basic mechanism studies revealed that hybrids 11 and 12a could induce apoptosis in MCF-7 cells through mitochondrial pathway. These hybrids induced morphological changes in MCF-7 cells, causing mitochondrial depolarization. These two hybrids also had the following effects: arrest of the cell cycle at the G2 phase; up regulation of Apaf-1, Bax, and cytochrome c; down regulation of Bcl-2 and Bcl-xL for both mRNA and protein; and increase of the expression for caspase-8 and -9. Finally, apoptotic effector caspase-3 was increased, which eventually caused nuclear apoptosis at least through an intrinsic pathway in the mitochondria. Additionally, hybrids 11 and 12a could specifically bind to estradiol receptor alpha in a dose-dependent manner.

Synthesis and characterization of microbial poly3-hydroxybutyric acid nanocarrier for curcumin as an antibreast cancer agent

Background and objective In a previous study, the authors produced, optimized, characterized, and purified the poly3-hydroxybutyric acid (PHB) using the locally isolated Bacillus flexus bacterial strain. The development of a biodegradable drug carrier as an efficient delivery system has received great interest over the past few decades. The objective of this study was to produce a nano-PHB carrier for curcumin to be more effective in tumor fighting. Materials and methods PHB was produced on the optimized medium by B. flexus strain. The nano-PHB form was produced using the nanoprecipitation technique. The size, shape, and characteristics of loaded curcumin nano-PHB particles were performed using zeta-potential, scanning electron microscopy, and Fourier transform infrared spectroscopy techniques. The antitumor effect of the nano-PHB loaded curcumin was performed using human breast adenocarcinoma MCF-7 cell line. Results and conclusion In this study, a naturally developed, biodegradable, and biocompatible nanosized carrier for curcumin-targeted delivery in breast-cancer cells with higher encapsulation efficiency (95.5%) was formulated. The size range of both free PHB and curcumin-loaded PHB was 237 and 260 nm respectively. The nanoparticles exhibited a spherical shape with no aggregation which is confirmed by electron microscopy, indicating a higher colloidal stability. The curcumin-loaded PHB nanocarrier showed a sustained drug release behavior. In-vitro anticancer assays showed the superiority of curcumin-loaded PHB nanocarrier over free curcumin for fighting breast cancer. These results show that the PHB biopolymer acts as an efficient carrier vehicle for the curcumin.

The N'-Substituted Derivatives of 5-Chloro-3-Methylisothiazole-4-Carboxylic Acid Hydrazide with Antiproliferative Activity.

Thanks to the progress in oncology, pharmacological treatment of cancer is gaining in importance and in the near future anti-cancer chemotherapeutics are expected to be the main method of treatment for cancer diseases. What is more, the search for new anti-cancer compounds with the desired application properties is constantly underway. As a result of designed syntheses, we obtained some new N’-substituted 5-chloro-3-methylisothiazole-4-carboxylic acid hydrazide derivatives with anticancer activity. The structure of new compounds was determined by mass spectrometry (MS), elemental analysis, proton nuclear magnetic resonance spectroscopy (1H-NMR), carbon nuclear magnetic resonance spectroscopy (13C-NMR), 1H-13C NMR correlations and infrared spectroscopy (IR). Moreover, the structures of the compounds were confirmed by crystallographic examination. The antiproliferative MTT tests for 11 prepared compounds was conducted towards human biphenotypic B cell myelomonocytic leukemia MV4-11. SRB test was used to examine their potential anticancer activity towards human colon adenocarcinoma cell lines sensitive LoVo, resistant to doxorubicin LoVo/DX, breast adenocarcinoma MCF-7 and normal non-tumorigenic epithelial cell line derived from mammary gland MCF-10A. The most active compound was 5-chloro-3-methyl-N′-[(1E,2E)-(3-phenyloprop-2-en-1-ylidene]isothiazole-4-carbohydrazide, which showed the highest antiproliferative activity against all tested cell lines.

The 5-hydrazino-3-methylisothiazole-4-carboxylic acid, its new 5-substituted derivatives and their antiproliferative activity

Currently, the basic method of treatment of colon cancer is surgery. The range of anticancer drugs used in the treatment of colorectal cancer is small and is based mainly on systemic combination chemotherapy. As a result of the designed syntheses, we received new isothiazole derivatives with anticancer activity. The synthesized 5-hydrazino-3-methylisothiazole-4-carboxylic acid has never been obtained before. It is also a substrate for the synthesis of its innovative derivatives, i.e. compounds that are Schiff bases. The identification of the structure of new compounds was carried out using mass spectrometry (MS), proton nuclear magnetic resonance spectroscopy (1H NMR), carbon nuclear magnetic resonance spectroscopy (13C NMR) and infrared spectroscopy (IR). Potential antitumor activity was confirmed in antiproliferative MTT and SRB tests. The selected, most biologically active substances were characterized by high selectivity towards leukemia and colon cancer cell lines. They caused high inhibition of proliferation of human biphenotypic B cell myelomonocytic leukemia MV4-11 (13 compounds), human colon adenocarcinoma cell lines sensitive LoVo (8 compounds) and resistant to doxorubicin LoVo/DX (12 compounds). However, in the conducted studies, their activity against breast adenocarcinoma MCF-7 and normal non-tumorigenic epithelial cell line derived from mammary gland MCF-10A was substantially lower. The result of this work is claimed Polish patent application.

EVALUATION OF PHYTOCHEMICAL COMPOUNDS IN Moringa oliefera Lam. EXTRACTS ON CYTOTOXICITY OF MCF-7 CELL LINE

Moringa olifera Lam. which called Miracle tree was an enormous usage of medical, nutritional and economic benefits so its leaves and roots extracts were vitro examined for phytochemicals contents, antioxidant, and cytotoxicity against MCF-7 cell line. Leaves and roots both extracts were estimate using 2,2-di phenyl-1-picryl hydrazyl (DPPH) radical scavenging assay and high performance liquid chromatography (HPLC) to determine phenolic and flavonoids compounds. The leaves aqueous and ethyl acetate extracts contained a significantly (p<0.05) more phenolic compounds than root extracts, while roots ethyl acetate extracts were significantly more active in DPPH assay comparing with aqueous extracts . However, the leaves aqueous extract and roots ethyl extracts were contained high values flavonoids compound but in case of phenolic compounds the aqueous roots ex tract recorded the greatest highest number followed by the leaves ethyl acetate extract. The ethyl acetate extractions for leaves and roots have a high inhibition percentage against breast adenocarcinoma MCF-7 cell line comparing with aqueous extracts.

Evaluation of nonlinear dynamics of the cell structure damage as a promising method for personalized cancer diagnostics

Background:Modulation interference microscopy is one of the promising technologies for early personalized cancer diagnostics, while it gives the possibility to obtain real-time images of living functioning cells at a nanometer resolution, as well as to assess spatio-temporal changes of their intracellular structures.Aim:To identify the markers of malignant transformation of cells based on a multiple scale spatio-temporal of the data obtained by lase interferometry duringin situregistration of changes in intracellular structures.Materials and methods:The study was performed with the breast adenocarcinoma MCF-7 cell line and human kidney epithelial cells HEK 293 provided by the N.N. Blokhin National Medical Research Centre of Oncology (Moscow, Russia). Changes in fluctuation of the living cell phase thickness were measured with a laser modulation interference microscope MIM-340 (PA UOMZ, Russia). The multifractal detrended fluctuation analysis (MF-DFA) was used to assess the results obtained.Results:By comparison of the scaling exponential spectra and corresponding spectra of the singular fluctuations in the minimal and maximal diameters of the phase pictures of HEK 293 cells and MCF-7 cells, it was shown that the cancer cell dynamics has definite monofractal properties: a linear dependency of the scaling exponentsτfrom the actualqparameter and “dotted” singularity spectrum (the spectral width does not exceed 0.1). The dynamics of healthy cell demonstrated multifractal properties, such as a non-linear dependencyτ(q)and a bell shaped singularity spectrum (the spectral width over 0.1).Conclusion:We have proposed a new approach to assess the intracellular structural damage during oncogenesis. The signs of monofractality are objective criteria of malignization. The results obtained seems promising as early diagnostic markers of cancer transformation (damage) of cells and determination of tumor cell sensitivity / resistance to anti-tumor agents in an individual patient.