Sclerotium rolfsii Lectin Induces Stronger Inhibition of Proliferation in Human Breast Cancer Cells than Normal Human Mammary Epithelial Cells by Induction of Cell Apoptosis

Sclerotium rolfsii lectin (SRL) isolated from the phytopathogenic fungus Sclerotium rolfsii has exquisite binding specificity towards O-linked, Thomsen-Freidenreich (Galβ1-3GalNAcα1-Ser/Thr, TF) associated glycans. This study investigated the influence of SRL on proliferation of human breast cancer cells (MCF-7 and ZR-75), non-tumorigenic breast epithelial cells (MCF-10A) and normal mammary epithelial cells (HMECs). SRL caused marked, dose-dependent, inhibition of proliferation of MCF-7 and ZR-75 cells but only weak inhibition of proliferation of non-tumorigenic MCF-10A and HMEC cells. The inhibitory effect of SRL on cancer cell proliferation was shown to be a consequence of SRL cell surface binding and subsequent induction of cellular apoptosis, an effect that was largely prevented by the presence of inhibitors against caspases -3, -8, or -9. Lectin histochemistry using biotin-labelled SRL showed little binding of SRL to normal human breast tissue but intense binding to cancerous tissues. In conclusion, SRL inhibits the growth of human breast cancer cells via induction of cell apoptosis but has substantially less effect on normal epithelial cells. As a lectin that binds specifically to a cancer-associated glycan, has potential to be developed as an anti-cancer agent

Molecular Interaction Studies of Zinc Sulphide Nanoparticles with DNA and its Consequence: A Multitechnique Approach

Molecular interaction studies between nanoparticles (NPs) and biomolecules are of great importance in the field of nanomedicine as they affect many physiological processes. Therefore, the interaction of zinc sulphide nanoparticles (ZnS NPs) with calf thymus deoxyribonucleic acid (CT DNA) and its significance was analyzed using ultraviolet (UV)–visible light, fluorescence, circular dichroism (CD), zeta potential, viscometry, electrochemical, and polymerase chain reaction methods. Fluorescence quenching analysis revealed that the fluorescence of ZnS NPs was quenched using CT DNA through a static quenching mechanism. The negative values of thermodynamic parameters (∆G, ∆H, and ∆S) showed that the binding process was spontaneous, exothermic, and van der Waals or hydrogen bonding plays an important role in the interaction of ZnS NPs with CT DNA. Thermal melting (Tm) studies indicated a decrease in the Tm of CT DNA, suggesting the destabilization of CT DNA upon interaction with ZnS NPs. In addition, the results obtained from competitive binding, zeta potential, CD, and viscometry measurements showed that the interaction of ZnS NPs with CT DNA is through groove binding. Electrochemical analysis further confirmed the observed results from various spectroscopic and other related studies, in which decrease in the redox peak current along with changes in peak potential (CV) and increase in the electrical resistance (EIS) indicated the interaction between ZnS NPs and CT DNA. Furthermore, PCR analysis using DNA polymerase revealed the potential of ZnS NPs to inhibit DNA replication in vitro. ZnS NP–CT DNA interaction studies can be explored to define new horizons in biomedical applications of ZnS NPs

SEMC mixed faculty recital, July 13, 1984. [sound recording].

Nanomaterials with enzyme-like activities (nanozymes) attracts significant interest due to their therapeutic potential for the treatment of various diseases. Herein, we report that a Mn3O4 nanozyme functionally mimics three major antioxidant enzymes, that is, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) and the multienzyme activity is size as well as morphologydependent. The redox modulatory effect of Mn3O4 plays a crucial role in protecting the cells from MPP+ induced cytotoxicity in a Parkinson disease (PD)-like cellular model, indicating that manganese-based nanomaterials having multienzyme activity can robustly rescue the cells from oxidative damage and thereby possess therapeutic potential to prevent ROS-mediated neurological disorders

Epigallocatechin gallate protects BEAS-2B cells from lipopolysaccharide-induced apoptosis through upregulation of gastrin-releasing peptide

Gastrin-releasing peptide (GRP) plays a major role in the development and maintenance of lung epithelial cells by promoting cell division, whereas its suppression causes growth arrest and apoptosis. The present study shows that human bronchial epithelial BEAS-2B cells challenged with lipopolysaccharide (LPS), an endotoxin from gram-negative bacteria, downregulated GRP expression and induced apoptosis via upregulation of p53 and active caspase-3, signifying the importance of GRP in lung epithelial cell survival. However, in the presence of epigallocatechin-3-gallate (EGCG), a polyphenol in green tea, BEAS-2B cells resisted LPS-induced apoptosis and restored the expression of GRP and its downstream effectors such as epidermal growth factor receptor and NF-kappa B, as analysed by immunoblotting and qPCR. Based on our findings, we objectify that cytoprotective functions of EGCG, via upregulation of GRP in cells challenged with LPS, are novel and can be further explored in a therapeutic point of view for diseases such as septic shock

Exploring the potential of newly synthesized 4-methyl-6-morpholino-pyrimidine derivatives as antiproliferative agents

In view of exploring the potential of pyrimidine derivatives as anticancer agents, a series of 4-methyl-6-morpholinopyrimidine derivatives was synthesised and characterised by NMR (H-1 & C-13), SC-XRD and mass spectral analysis. The in vitro anticancer activity of these compounds was investigated using different human cancer cell lines, namely HeLa (cervix), NCI-H460 (lung), MCF-7 (breast), HepG2 (liver) and IMR-32 (brain). Compounds 4c and 5h exhibited potent anticancer activity in a dose-dependent manner as compared to other derivatives, with IC50 values of 5.88 +/- 1.22 and 6.11 +/- 2.12 mu M on HeLa and NCI-H460, cells respectively. The inhibitory effect of 4c and 5h on cancer cell proliferation was shown to be a consequence of reactive oxygen species (ROS) generation and subsequent induction of cellular apoptosis, as evidenced by an increase in hypodiploid (subG1) population, early apoptotic cell population, caspase-3/7 activity, loss of mitochondrial membrane potential and degradation of nuclear DNA. Furthermore, molecular docking studies revealed that 4c and 5h compounds bind to the ATP binding pocket of the mammalian target of rapamycin (mTOR). Based on our results, we conclude that 4-methyl-6-morpholinopyrimidine derivatives prevent cancer cell proliferation by inducing apoptosis and thus have potential to be further explored for anticancer properties

SRL induces cell apoptosis.

<p>(<b>A</b>) Annexin V cell surface binding in MCF-7 cells after incubation with SRL (20 µg/ml) for 24, 36 or 48 h. Percentages of cells in each quadrant are shown as inserts. The graph indicates percentage of the cell population in different phases. (<b>B</b>) Effect of SRL on cell cycle. MCF-7 cells were exposed to SRL (20 µg/ml) for 24, 36 and 48 h before the cellswere stained with propidium iodide and DNA content was measured by flow cytometry. The graph indicates percentage of cells in subG1, G1, S, and G2–M phases of the cell cycle.</p

Sepharose-conjugated SRL induced growth inhibition of breast cancer cells.

<p>(<b>A</b>) SRL shows strong binding to MCF-7 cells and very weak binding to (<b>B</b>) HMEC. (<b>C</b>) MCF-7 cells were incubated without or with SRL or Sepharose-SRL (C-SRL), at equivalent concentrations to SRL with 128 and 256 hemagglutination units (HAU) activity for 72 h before the cell proliferation was assessed by Calcein AM. Data represent Mean ±SD of triplicateexperiments. *** p<0.0001 when compared to control.</p

SRL histochemistry to normal and cancerous human breast tissues.

<p>SRL histochemistry was performed in human breast (normal, primary cancer and metastatic) tissue samples. SRL shows weak binding to normal human breast tissues but strong binding to primary cancer and metastatic breast tissues. All the images were obtained with 100X magnification. Arrows point to SRL binding to apical surface of the secretory gland epithelia. Representative images of both Haematoxylin-Eosin and Biotin-SRL staining are shown. SRL binding was evaluated through optical analysis by measuring the mean area of stained cells scored arbitrarily as intense (+++), moderate (++), light (+) and no staining (−).</p

SRL inhibits proliferation of human breast cancer cells.

<p>(<b>A</b>). SRL causes dose-dependent inhibition of human breast cancer MCF-7 and ZR-75 cell proliferation. The cells were incubated with or without different concentrations of SRL for 72 h. SRL-mediated cell growth inhibition is prevented by the presence of TF-expressing glycoprotein: MCF-7and ZR-75 cells were incubated with or without 20 µg/ml SRL in the presence of 100 µg/ml asialo bovine submaxillarymucin (aBSM) for 72 h. SRL caused time-dependent inhibition of MCF-7 cell proliferation. (<b>B</b>). The MCF-7 cells were incubated with or without different concentrations of SRL, BSA (40 µg/ml) and TBS for 24, 48 and 72 h before cell proliferation was assessed. Data represent Mean ±SD of triplicate determinations from three different assessments. *p<0.05; ***p<0.001.</p