In vitro cytotoxic effect of urtica dioica extracts on acute myelogenous leukemia cell line (kg-1)

Background: Urtica dioica is one of the medicinal herbs with many uses in treating various diseases. In some studies, its antiproliferative and apoptotic effects on cancer cell lines have been shown. Therefore, the evaluation of U. dioica effect was performed on KG-1 cell line for acute myelogenous leukemia (AML) for the first time in this study.Materials and Methods: KG-1 cell line was treated by various extracts (aqueous, hydroalcoholic, chloroform and ethyl acetate) of U. dioica aerial parts and roots in different concentrations. Metabolic activity of extracts on cell line was assessed by MTT assay. To evaluate the percentage of apoptotic cells, the flow cytometry was performed by FITC Annexin V-PI apoptosis detection kit in KG-1 cell line treated with root chloroform (UDC-R) and ethyl acetate (UDE-R) extracts. The results have been reported as percentage of cell viability and IC50.Results: Based on MTT results, the strongest IC50 in KG-1 cell line (219.361μg/ml) was related to UDC-R. The flow cytometric analysis showed that UDC-R and UDE-R in IC50 concentration induced early (53.6% and 57.4%, respectively) and late (27% and 33.2%, respectively) apoptosis in KG-1 cells after 24 hrs. The inhibition of cell proliferation by various extracts of U. dioica was dependent on concentration (p=0.000).Conclusion: Flow cytometric analysis confirmed that UDC-R and UDE-R extracts affect on proliferation reduction of KG-1 cells by activating the apoptotic pathway

The comparison of the apoptosis effects of titanium dioxide nanoparticles into MDA-MB-231 cell line in microgravity and gravity conditions

Objective (s): Gravity could affect some system features and perform directly as an organizing field factor. Recent investigations have examined the titanium dioxide nanoparticles (TiO2 NPs) in biomedical applications, mostly in the cancer treatment field. This study aimed to evaluate the effects of simulated microgravity combined with TiO2 NPs in MDA-MB-231 cells proliferation for the first time. In other words, this study examined the utility of the microgravity environment in nano-therapy. Materials and Methods: The MDA-MB-231 human breast cancer cell line and TiO2 NPs were purchased. The 2D clinostat was applied for the simulation of the microgravity. The morphological studies, MTT cytotoxicity assay, Acridine orange/Ethidium bromide double staining studies and flow cytometry analysis were utilized.Results: The MTT assay, the morphological studies, Acridine orange/Ethidium bromide double staining studies and flow cytometry analysis confirmed the apoptosis-inducing effect of microgravity in combination with TiO2 NPs. The IC50 of simulated microgravity in the presence of TiO2 NPs was determined to be 130 µM. Furthermore, MDA-MB-231 cells exposed to microgravity adopted a different phenotype. Conclusion: Based on our observation, although the relative mechanisms need to be explored further, microgravity can strictly affect the TiO2 NPs effects on MDA-MB-231 cells. The significance of this study lied in the fact that simulating microgravity can be a powerful physical cure for cancer therapy and open new horizons for the studies in the field of biology, biophysics, and medicine

Synthesis, Cytotoxicity Assessment, and Molecular Docking of 4-Substituted-2-p-tolylthiazole Derivatives as Probable c-Src and erb Tyrosine Kinase Inhibitors

In the current project we focused on the synthesis of 4-Substituted-2-p-tolylthiazole derivatives. Cytotoxicity of synthesized compounds were evaluated against T47D breast cancer cell line and also all of the final compounds 3−7 were docked into the active site of c-Src and erb tyrosine kinases. Compound 4 was the most potent derivative in cytotoxicity assay (IC50 = 2.5 µg/mL) and it was also the most potent inhibitor of erb tyrosine kinase (Binding free energy: −10.18 kcal/mol).(doi: 10.5562/cca1939

Synthesis and Evaluation of Antiproliferative Activity of Substituted N-(9-oxo-9H-xanthen-4-yl)benzenesulfonamides

Several novel N-(9-oxo-9H-xanthen-4-yl)benzenesulfonamides derivatives were prepared as potential antiproliferative agents. The in vitro antiproliferative activity of the synthesized compounds was investigated against a panel of tumor cell lines including breast cancer cell lines (MDA-MB-231, T-47D) and neuroblastoma cell line (SK-N-MC) using MTT colorimetric assay. Etoposide, a well-known anticancer drug, was used as a positive standard drug. Among synthesized compounds, 4-methoxy-N-(9-oxo-9H-xanthen-4-yl)benzenesulfonamide (5i) showed the highest antiproliferative activity against MDA-MB-231, T-47D, and SK-N-MC cells. Furthermore, pentafluoro derivatives 5a and 6a exhibited higher antiproliferative activity than doxorubicin against human leukemia cell line (CCRF-CEM) and breast adenocarcinoma (MDAMB- 468) cells. Structure-activity relationship studies revealed that xanthone benzenesulfonamide hybrid compounds can be used for development of new lead anticancer agents

Synthesis and Evaluation of Cytotoxic Activity of Substituted N-(9-oxo-9H-xanthen-4-yl)benzenesulfonamides

Several novel N-(9-oxo-9H-xanthen-4-yl)benzenesulfonamides derivatives were prepared as potential antiproliferative agents. The in vitro antiproliferative activity of the synthesized compounds was investigated against a panel of tumor cell lines including breast cancer cell lines (MDA-MB-231, T-47D) and neuroblastoma cell line (SK-N-MC) using MTT colorimetric assay. Etoposide, a well-known anticancer drug, was used as a positive standard drug. Among synthesized compounds, 4-methoxy-N-(9-oxo-9H-xanthen-4-yl)benzenesulfonamide (5i) showed the highest antiproliferative activity against MDA-MB-231, T-47D, and SK-N-MC cells. Furthermore, pentafluoro derivatives 5a and 6a exhibited higher antiproliferative activity than doxorubicin against human leukemia cell line (CCRF-CEM) and breast adenocarcinoma (MDA-MB-468) cells. Structure-activity relationship studies revealed that xanthone benzenesulfonamide hybrid compounds can be used for development of new lead anticancer agents

Antioxidant activity and protective effects of Saccharomyces cerevisiae peptide fractions against H2O2-induced oxidative stress in Caco-2 cells

Oxidative stress is one of the most causes of some severe diseases and the spoilage of foods. Protein hydrolysates containing antioxidant peptides are a suitable candidate to replace synthetic antioxidant. In the present study, the in vitro and cellular antioxidant properties of Saccharomyces cerevisiae protein hydrolysate and the peptide fractions have been reported. The peptide protective role was evaluated in H2O2-stimulated Caco-2 cells to consider cell viability, cellular lipid and protein oxidation, and the level of cellular antioxidant enzymes such as Catalase (CAT) and Glutathione-S-transferase (GST). The peptide fractions showed a significant ferric reducing antioxidant power (67.10-93.52 mu m FeSO4/mg protein), and < 3 kDa peptide fraction with 59.5% inhibitory effect on the 7th day, exhibited the most inhibitory activity toward linoleic acid peroxidation. Ultrafiltered fractions ( < 3 kDa and 3-5 kDa) significantly (P <= 0.05) decreased the levels of malondialdehyde (MDA) and protein carbonyl and the production of CAT and GST enzymes as protective responses of cells under oxidative stress by H2O2. This study confirms the antioxidant activity of yeast protein hydrolysate and peptide fractions and their potential to reduce cellular oxidative stress and thus validates their potential use as a valuable ingredient of functional foods

In vitro and in silico studies of novel synthetic ACE-inhibitory peptides derived from Saccharomyces cerevisiae protein hydrolysate

The structure-function relation of YR-10 (YGKPVAVPAR) was investigated by synthesizing four structural analogs of that including YHR-10 (YGKHVAVHAR), GA-8 (GKPVAVPA), GHA-8 (GKHVAVHA), and PAR-3 (PAR). GA-8 (GKPVAVPA) was synthesized on the basis of simulated enzymatic gastrointestinal digestion performed by bioinformatics tools (expasy-peptide cutter). This study explains the molecular mechanisms for the interaction of synthetic peptides with ACE. The IC50 values of each were 139.554 +/- 2.3, 61.91 +/- 1.2, 463.230 +/- 3.56, 135.135 +/- 2.1, 514.024 +/- 5.86 mu M, respectively. Results indicated that Pro replacement with His in YR-10 and GA-8 increased ACE inhibitory activity respectively, by 55.63% and 70.82%. Removal of Tyr and Arg from respectively N and C terminal positions of YR-10, following in silico simulated gastrointestinal digestion caused the 3.31 fold decrease in ACE inhibitory activity. YHR-10 showed the best docking poses, and GHA-8 exhibited interaction with Zn2+. Lineweaver-Burk plots of most active peptides suggest that they act as noncompetitive inhibitors against ACE

The stability of antioxidant and ACE-inhibitory peptides as influenced by peptide sequences

As the structural characteristics of peptides affect their functional properties, they are an important factor for peptide stability. The stability characteristic was investigated in two groups of synthetic peptides, analogues of VLSTSFPPK (VL-9). The latter was previously purified from Kluyveromyces marxianus protein hydrolysate. In the first group, the replacement impact of Pro in antepenultimate position with Tyr, Cys and His on antioxidant stability against heat, NaCl, and pH and in the second group, the replacement effect of Lys in C-terminal with Trp, Tyr, and Phe on the stability of antihypertensive activity under gastrointestinal digestion were studied. Pro containing peptide (VL-9) showed the highest antioxidant stability against heat and salt. Despite the positive effect of Cys in antioxidant activity of peptides (VCK-9), it decreased the heat and salt stability. Tyr increased the ABTS cation radical scavenging activity and resulting peptide had the same thermal stability as the primary peptide and higher sensitivity to salt. Despite not significant effect of His on the antioxidant activity, it caused a slight instability against heat and salt. The antioxidant peptides studied showed the highest stability at neutral pH. The higher hydrophilicity of Lys in the peptide sequence caused higher ACE-inhibitory stability in simulated GI digestion