Development of near-infrared region luminescent N-acetyl-L-cysteine-coated Ag2S quantum dots with differential therapeutic effect

Aim: N-acetyl-L-cysteine (NAC) is a free radical scavenger. We developed NAC-coated Ag2S (NAC-Ag2S) quantum dot (QD) as an optical imaging and therapeutic agent. Materials & methods: QDs were synthesized in water. Their optical imaging potential and toxicity were studied in vitro. Results: NAC-Ag2S QDs have strong emission, that is tunable between 748 and 840 nm, and are stable in biologically relevant media. QDs showed significant differences both in cell internalization and toxicity in vitro. QDs were quite toxic to breast and cervical cancer cells but not to lung derived cells despite the higher uptake. NAC-Ag2S reduces reactive oxygen species (ROS) but causes cell death via DNA damage and apoptosis. Conclusion: NAC-Ag2S QDs are stable and strong signal-generating theranostic agents offering selective therapeutic effects

The ATP Assay, but not the MTT assay, Detects Further Cytotoxicity of the Combination of Anthracycline-based Therapy with Histone Deacetylase Inhibitor (Valproic Acid) in Breast Cancer Cells

Purpose: It has been investigated that whether or not the combination of valproic acid (a histone deacetylase inhibitor) with anthracycline-based chemotherapy (FEC: 5-fluorouracil+epirubicine+ cyclophosphamide) would change the cytotoxic effects of FEC in breast cancer cells

The Effects of Fenarimol and Methyl Parathion on Glucose 6-Phosphate Dehydrogenase Enzyme Activity in Rats

Fenarimol and methyl parathion are pesticides that have been used in agriculture for several years. These pesticides have significant effects on environmental and human health. Therefore, we investigated the effects of methyl parathion and fenarimol on glucose 6-phosphate dehydrogenase (EC 1.1.1.49) enzyme activity in rats. The glucose 6- phosphate dehydrogenase is the first enzyme of the pentose phosphate pathway and it is important in detoxifying reactions by NADPH generated. In this study, wistar albino rats administrated with methyl parathion (7 mg kg–1) and fenarimol (200 mg kg−1) by intraperitoneally for different periods (2, 4, 8, 16, 32, 64, and 72 h). The glucose 6-phosphate dehydrogenase enzyme activity was assayed in liver, kidney, brain, and small intestine in male and female rats. The exposure of fenarimol and methyl parathion caused increase of glucose 6-phosphate dehydrogenase enzyme activity in rat tissues, especially at last periods. We suggest that this increment of enzyme activity may be the reason of toxic effects of fenarimol and methyl parathion

A Glance at the methods for detection of apoptosis qualitatively and quantitatively

While programmed cell death, apoptosis, occurs as a necessary and natural event for multicellular organisms, necrosis is a form of unplanned cell death as a result of pathological or chemical trauma. There are numerous molecular and morphological differences between these two forms of cell death, whose decision is based on the type and dose of the stress. As apoptosis is critical for homeostasis of an organism, i.e. for development to adult stage, disease progression, or response to different stimuli, it is being studied more extensively in the area of basic research and clinics, and the need for quick detection of apoptosis and well established criteria for the discrimination of apoptosis have also gained more popularity. Here, we review our knowledge on the most commonly used methods for both qualitatively and quantitatively measuring apoptosis, including morphological imaging (i.e. through light, fluorescence, phase contrast or electron microscopy), immunohistochemical (i.e. Annexin V-FITC, TUNEL, M30 antigen or caspase 3 detection), biochemical (i.e. DNA-or protein-based electrophoresis or flow cytometry-based methods), immunological (i.e. ELISA), and molecular biology techniques (i.e. array-based techniques) while focusing on the differences for distinction between the two forms of cell death. Indeed, one has to confirm that cell death occurs through apoptosis based on more than one of these protocols depending on the specific purpose of the user

A Glance at the methods for detection of apoptosis qualitatively and quantitatively

While programmed cell death, apoptosis, occurs as a necessary and natural event for multicellular organisms, necrosis is a form of unplanned cell death as a result of pathological or chemical trauma. There are numerous molecular and morphological differences between these two forms of cell death, whose decision is based on the type and dose of the stress. As apoptosis is critical for homeostasis of an organism, i.e. for development to adult stage, disease progression, or response to different stimuli, it is being studied more extensively in the area of basic research and clinics, and the need for quick detection of apoptosis and well established criteria for the discrimination of apoptosis have also gained more popularity. Here, we review our knowledge on the most commonly used methods for both qualitatively and quantitatively measuring apoptosis, including morphological imaging (i.e. through light, fluorescence, phase contrast or electron microscopy), immunohistochemical (i.e. Annexin V-FITC, TUNEL, M30 antigen or caspase 3 detection), biochemical (i.e. DNA-or protein-based electrophoresis or flow cytometry-based methods), immunological (i.e. ELISA), and molecular biology techniques (i.e. array-based techniques) while focusing on the differences for distinction between the two forms of cell death. Indeed, one has to confirm that cell death occurs through apoptosis based on more than one of these protocols depending on the specific purpose of the user

Anti-proliferative and Apoptotic Effects of Coordination Compounds of Zinc(II), Palladium(II), and Platinum(II) with Tridentate 4-(6-hydroxyphenyl)-2,6-di(thiazol-2-yl)pyridine

The mononuclear coordination compounds, [Zn(L)Cl-2] (1), [Pd(L)Cl]Cl (2), and [Pt(L)Cl]Cl (3) (L) is a tridentate-coordinated of 4-(6-hydroxyphenyl)-2,6-di(thiazol-2-yl)pyridine) were synthesized and characterized by different spectroscopic methods (FTIR, MALDI-TOF-MS, H-1 NMR, C-13 NMR, and UV/Vis). By using density functional theory (DFT) and time-dependent DFT (TD-DFT) methods, the geometrical parameters, UV/Vis absorption spectra, and infrared vibrational frequencies for the investigated compounds were explored. Anticancer activities of these compounds were determined by SRB viability assay in human lung (A549 and H1299), prostate (LNCAP), colorectal (HT-29), breast cancer (MDA-MB-231) and healthy bronchial (BEAS-2B), breast (MCF-10A), colon (CCD-18Co), and prostate (WPMY-1) epithelial cells. Caspase 3/7 activity, cleaved cytokeratin-18, and PARP levels were measured to determine apoptosis in the metal compounds found to be effective. Among the compounds, 1 showed a selective inhibiting effect and induced apoptosis on the cancer cells, thus further analyses are needed to evaluate its antitumor/anticancer activity.The authors are grateful to the Research Fund of Zonguldak Bulent Ecevit University (Project Number: 2020-72118496-05) and the Research Fund of Bursa Uludag University (Project Number: FHIZ-2021-515) for the financial support under the project. Oguzhan AKGUN is a Ph.D. student financed by the Council of Higher Education (YOEK) 100/2000 Ph.D. Scholarship Program. Computer time provided by TUBITAK ULAKBIM TRUBA Resources is gratefully acknowledged.Research Fund of Zonguldak Bulent Ecevit University [2020-72118496-05]; Research Fund of Bursa Uludag University [FHIZ-2021-515]; Council of Higher Education (YOEK) [100/2000]; TUBITAK ULAKBIM TRUBA Resource

Soloxolone methyl, as a 18 beta H-glycyrrhetinic acid derivate, may result in endoplasmic reticulum stress to induce apoptosis in breast cancer cells

Being one of the leading causes of cancer death among women, various chemotherapeutic agents isolated from natural compounds are used in breast cancer treatment and consequently studies to develop new drugs still continue. There are several studies on 18 beta H-glycyrrhetinic acid, a secondary metabolite which is found in Glycyrrhiza glabra (liquorice roots), as a potential anticancer agent. In this study, the cytotoxic and apoptotic effects of Soloxolone methyl compound, a semisynthetic derivative of 18 beta H-glycyrrhetinic acid were investigated on breast cancer cells (MCF-7, MDA-MBA-231). Soloxolone methyl is found to be cytotoxic on both MCF-7 and MDA-MBA-231 breast cancer cells by inducing apoptosis. Especially in MDA-MB-231 cells apoptosis is detected to be triggered by ER stress. The antigrowth effects of Soloxolone methyl were determined using MTT and ATP assays. To identify the mode of cell death (apoptosis/necrosis), fluorescent staining (Hoechst 33342 and Propidium iodide) and caspase-cleaved cytokeratin 18 (M30-antigen) analyses were used. In addition, apoptosis was investigated on gene and protein levels by PCR and Western Blotting. Soloxolone methyl decreased cell viability on cells in a dose and time-dependent manner and induced apoptosis markers. An increase on apoptotic proteins related to endoplasmic reticulum stress (IRE1-alpha, Bip, CHOP) was also determined in MDA-MB-231 cells. Moreover, an increase of apoptotic gene expressions was determined in both cells treated with Soloxolone methyl. Advance analyses should be performed to elucidate the potential of Soloxolone methyl as an anticancer agent in breast cancer treatment

Investigation of the efficacy of paclitaxel on some miRNAs profiles in breast cancer stem cells

Understanding of the functions of microRNAs in breast cancer and breast cancer stem cells have been a hope for the development of new molecular targeted therapies. Here, it is aimed to investigate the differences in the expression levels of let-7a, miR-10b, miR-21, miR-125b, miR-145, miR-155, miR-200c, miR-221, miR-222 and miR-335, which associated with gene and proteins in MCF-7 (parental) and MCF-7s (Mammosphere/stem cell-enriched population/CD44+/CD24-cells) cells treated with paclitaxel. MCF7-s were obtained from parental MCF-7 cells. Cytotoxic activity of paclitaxel was determined by ATP assay. Total RNA isolation and cDNA conversion were performed from the samples. Changes in expression levels of miRNAs were examined by RT-qPCR. Identified target genes and proteins of miRNAs were analyzed with RT-qPCR and western blot analysis, respectively. miR-125b was significantly expressed (2.0946-fold; p = 0.021) in MCF-7s cells compared to control after treatment with paclitaxel. Downregulation of SMO, STAT3, NANOG, OCT4, SOX2, ERBB2 and ERBB3 and upregulation of TP53 genes were significant after 48 h treatment in MCF-7s cells. Protein expressions of SOX2, OCT4, SMAD4, SOX2 and OCT4 also decreased. Paclitaxel induces miR-125b expression in MCF-7s cells. Upregulation of miR-125b may be used as a biomarker for the prediction of response to paclitaxel treatment in breast cancer

Mixed ligand complexes of Co(II), Ni(II) and Cu(II) with quercetin and diimine ligands: synthesis, characterization, anti-cancer and anti-oxidant activity

In this work, mixed ligand complexes of Co(II) Ni(II) and Cu(II) were synthesized using quercetin and diimine (1,10-phenanthroline or 2,2 '-bipyiridine) ligands. The obtained Ni(II) and Co(II) complexes are new and the Cu(II) complexes are synthesized by different method from the literature. The characterization of complexes was performed by elemental analysis, thermogravimetric analysis, ESI-MS, UV-visible and infrared spectral analyses, magnetic susceptibility and molar conductivity measurements. It was found that quercetin, diimine and metal(II) ion form 1:1:1 complexes. Resulting data supported octahedral geometry for Ni(II) and Co(II) complexes and square pyramidal geometry for Cu(II) complexes. The proposed compositions are [Co(queH-1)Cl(phen)(H2O)]center dot 2H(2)O (1, queH = quercetin, phen = 1,10-phenanthroline), [Ni(queH-1)Cl(phen)(H2O)]center dot 2H(2)O (2), [Cu(queH-1)Cl(phen)]center dot 2.5H(2)O (3) and [Cu(queH-1)Cl(bpy)]center dot 2H(2)O (4, bpy = 2,2 '-bipyiridine). Antioxidant capacity and total phenolic content of complexes measured by Folin-Ciocalteu and ABTS methods. Anti-cancer effect of these compounds were tested against different cancer cells (A549, PC-3, HeLa and MCF-7). Apoptosis identified by the fluorescence imaging, caspase cleaved cytokeratin-18 and flow cytometry analysis (annexin V, caspase 3/7, mitochondria membrane potential and oxidative stress). As a result, Cu(II) complexes are more effective than the other compounds and Complex 3 is a promising anti-cancer compound against breast cancer MCF-7 and MDA-MB-231 cells (IC50 values are 2.4 and 5.4 mu M for 48 h, respectively). Flow cytometry analysis exhibited that Complex 3 caused apoptosis in MCF-7 cells. These results support that Complex 3 has anticancer activity and can be a potential anticancer agent especially in breast cancer