Glutamine regulates ovarian cancer cell migration and invasion through ETS1.

Cancer cells are dependent on glutamine for their metabolism and growth. Despite being the most abundant amino acid in the blood, glutamine deprivation occurs in the core of the tumor rendering less access to glutamine to the nearby tumor cells. Tumor cells mostly use the glutamine for mitochondrial oxidative phosphorylation (OXPHOS) to produce energy and the ingredients of the biomass required for the highly proliferating and metastatic ovarian cancer cells.

Glutamine deficiency promotes stemness and chemoresistance in tumor cells through DRP1-induced mitochondrial fragmentation.

Glutamine is essential for maintaining the TCA cycle in cancer cells yet they undergo glutamine starvation in the core of tumors. Cancer stem cells (CSCs), responsible for tumor recurrence are often found in the nutrient limiting cores. Our study uncovers the molecular basis and cellular links between glutamine deprivation and stemness in the cancer cells.

Power of an Organic Electron Acceptor in Modulation of Intracellular Mitochondrial Reactive Oxygen Species: Inducing JNK- and Caspase-Dependent Apoptosis of Cancer Cells.

Here, we demonstrate an interesting strategy of modulating mitochondrial reactive oxygen species (ROS) using the organic electron acceptor molecule carbonyl-bridged bithiazole attached with bis-trifluoroacetophenone (BBT). This molecule was found to affect complex I activity. It has the propensity to bind close to the flavin mononucleotide site of complex I of mitochondria where it traps electron released from nicotinamide adenine dinucleotide (NADH) and elevates intracellular ROS, which suggests that the bridged carbonyl in BBT plays a crucial role in the acceptance of electron from NADH.

Potential Neuroprotective Peptide Emerged from Dual Neurotherapeutic Targets: A Fusion Approach for the Development of Anti-Alzheimer's Lead.

Amyloid-beta (Aβ) peptide misfolds into fibrillary aggregates (β-sheet) and is deposited as amyloid plaques in the cellular environment, which severely damages intraneuronal connections leading to Alzheimer's disease (AD) pathogenesis. Furthermore, neurons are rich in tubulin/microtubules, and the intracellular network of microtubules also gets disrupted by the accumulation of Aβ fiber in the brain. Hence, development of new potent molecules, which can simultaneously inhibit Aβ fibrillations and stabilize microtubules, is particularly needed for the efficient therapeutic application in AD.

Why Microtubules Should Be Considered as One of the Supplementary Targets for Designing Neurotherapeutics.

In the past decade of research, drugs targeting amyloid beta (Aβ) have failed in clinical amelioration of Alzheimer's disease (AD). This has led to researchers searching for more attractive targets. Here, we discuss one such approach of developing future neurotherapeutics by targeting microtubules.

Glial-Neuron Transformation by "Chemical Cocktail".

Repairing of brain damage is a challenging task due to the limited regenerative potential of complex network of neurons interspersed with glial cells. To address this issue, a number of approaches are in progress. Here we discuss a fascinating approach in which reactive astrocytes generated during any brain injury can be transformed into functional neurons using a mixture of small molecules or "chemical cocktail".

Discovery of Neuroregenerative Peptoid from Amphibian Neuropeptide That Inhibits Amyloid-β Toxicity and Crosses Blood-Brain Barrier.

Development of potential therapeutics for Alzheimer's disease (AD) requires a multifaceted strategy considering the high levels of complexity of the human brain and its mode of function. Here, we adopted an advanced strategy targeting two key pathological hallmarks of AD: senile plaques and neurofibrillary tangles. We derived a lead short tetrapeptide, Ser-Leu-Lys-Pro (SLKP), from a dodeca-neuropeptide of amphibian (frog) brain.

Neurosphere Development from Hippocampal and Cortical Embryonic Mixed Primary Neuron Culture: A Potential Platform for Screening Neurochemical Modulator.

Reconstitution of a complex biological structure or system following a simple and facile strategy using minimum physiochemical cues is challenging for an in-depth understanding of the system. In particular, the brain is a highly sophisticated and complex network of trillions of neurons and glial cells that controls function of our body. Understanding this complex machinery requires an innovative and simple bottom-up approach.

Genesis of Neuroprotective Peptoid from Aβ30-34 Inhibits Aβ Aggregation and AChE Activity.

Aβ peptide and hyper-phosphorylated microtubule associated protein (Tau) aggregation causes severe damage to both the neuron membrane and key signal processing microfilament (microtubule) in Alzheimer's disease (AD) brains. To date, the key challenge is to develop nontoxic, proteolytically stable amyloid inhibitors, which can simultaneously target multiple pathways involved in AD. Various attempts have been made in this direction; however, clinical outcomes of those attempts have been reported to be poor.

Peptide-Based Acetylcholinesterase Inhibitor Crosses the Blood-Brain Barrier and Promotes Neuroprotection.

Design and development of acetylcholinesterase (AChE) inhibitor has tremendous implications in the treatment of Alzheimer's disease (AD). Here, we have adopted a computational approach for the design of a peptide based AChE inhibitor from its active site. We identified an octapeptide, which interacts with the catalytic anionic site (CAS) of AChE enzyme and inhibits its activity.

FGF9-induced ovarian cancer cell invasion involves VEGF-A/VEGFR2 augmentation by virtue of ETS1 upregulation and metabolic reprogramming.

Ovarian cancer (OC) renders its lethality to enhanced metastasis and late detection. A plethora of growth factors including Vascular Endothelial Growth Factor (VEGF) and Fibroblast Growth Factor (FGF) stimulated signaling pathways regulate the invasive/metastatic behavior of ovarian tumors contributing to its aggressiveness. Autocrine VEGF-functioning by virtue of upregulated VEGFR2 contributes to the invasiveness of OC cells by modulating the MMPs.

Stemness and chemoresistance are imparted to the OC cells through TGFβ1 driven EMT.

Ovarian cancer (OC) is the fourth most common gynecological malignancy due to its highly aggressive, recurrent, and drug-resistant nature. The last two features are rendered by the presence of cancer stem cells (CSCs). Factors like TGFβ1 and their downstream signaling pathways are upregulated in most cancers and are known to induce EMT and stemness, but the exact mechanisms underlying the process remain unelucidated.

Live Cell Microscopy: A Physical Chemistry Approach.

Probing dynamics of intracellular components using physical chemistry techniques is a remarkable bottom-up approach for understanding the structures and functions of a biological cell. In this "Feature Article", we give an overview on local polarity, solvation, viscosity, acid-base property, red-ox processes (thiol-disulfide exchange), and gene silencing at selected intracellular components inside a live cell. Significant differences have been observed between cancer cells and their noncancer counterparts.

Crafting of Neuroprotective Octapeptide from Taxol-Binding Pocket of β-Tubulin.

Microtubules play a crucial role in maintaining the shape and function of neurons. During progression of Alzheimer's disease (AD), severe destabilization of microtubules occurs, which leads to the permanent disruption of signal transduction processes and memory loss. Thus, microtubule stabilization is one of the key requirements for the treatment of AD.

Mesenchymal splice isoform of CD44 (CD44s) promotes EMT/invasion and imparts stem-like properties to ovarian cancer cells.

Increased metastasis and a precipitous recurrence contribute to the lethality of ovarian cancer (OC). Several molecular mechanisms including aberrant-splicing have been closely associated with the extent of cancer progression. Numerous gene transcripts are differentially spliced in cancer cells, CD44 being one of them.

Co-Activation of TGFβ and Wnt Signalling Pathways Abrogates EMT in Ovarian Cancer Cells.

Background/aims: The aggressive property of ovarian cancer (OC) in terms of epithelial-mesenchymal transition (EMT), proliferation and metastasis are of major concern. Different growth factors including TGFβ are associated with regulating these molecular events but the underlying mechanisms remain unclear. The aim of this report is to decipher the regulation of EMT by co-activation of TGFβ and Wnt signalling cascades in gaining malignancy.

Biodegradable Neuro-Compatible Peptide Hydrogel Promotes Neurite Outgrowth, Shows Significant Neuroprotection, and Delivers Anti-Alzheimer Drug.

A novel neuro-compatible peptide-based hydrogel has been designed and developed, which contains microtubule stabilizing and neuroprotective short peptide. This hydrogel shows strong three-dimensional cross-linked fibrillary networks, which can capture water molecules. Interestingly, this hydrogel serves as excellent biocompatible soft material for 2D and 3D (neurosphere) neuron cell culture and provides stability of key cytoskeleton filaments such as microtubule and actin.

Apoferritin Nanocage Delivers Combination of Microtubule and Nucleus Targeting Anticancer Drugs.

An ideal nano drug delivery agent must be potent enough to carry high dose of therapeutics and competent enough in targeting specific cell of interest, having adequate optimized physiochemical properties and biocompatibility. Carrying differentially polar therapeutics simultaneously will make them superior in their class. However, it is of enormous challenge to the researchers to find such a unique nanocarrier and to engineer all of the above-mentioned features into it.

Synergistic Anticancer Effect of Peptide-Docetaxel Nanoassembly Targeted to Tubulin: Toward Development of Dual Warhead Containing Nanomedicine.

Microtubule dynamics play a crucial role in cancer cell division. Various drugs are developed to target microtubule. Although a few of them show potential in treatment of cancer, but success rate is limited due to their poor bioavailability and lack of specificity.

Amyloid beta peptides inside a reconstituted cell-like liposomal system: aggregation, FRET, fluorescence oscillations and solvation dynamics.

Aggregations of amyloid-beta (Aβ) peptides were studied inside a reconstituted cell like liposomal system using time-resolved confocal microscopy. Fluorescence correlation spectroscopy (FCS) and confocal images indicate that Aβ forms a very large aggregate in bulk and more efficiently, in the bilayer region of the liposome, respectively. The aggregates formed inside the liposome gradually migrate out to bulk water.

Novel tubulin-targeted cell penetrating antimitotic octapeptide.

An antimitotic cell penetrating octapeptide containing single Arg amino acid is discovered, which strongly binds with the exchangeable GTP/GDP binding site of tubulin, inhibits tubulin polymerization, reduces kinesin driven microtubule motility, activates apoptotic and mitotic check point proteins, induces apoptotic death and significantly inhibits the multicellular tumor spheroid growth of HeLa cells.

Thioredoxin interacting protein mediates lipid-induced impairment of glucose uptake in skeletal muscle.

Insulin resistance (IR) is an important determinant of type-2 diabetes mellitus (T2DM). Free fatty acids (FFAs) induce IR by various mechanisms. A surfeit of circulating FFA leads to intra-myocellular lipid accumulation that induces mitochondrial ROS generation and worsens IR.

Binding studies of creatinine and urea on iron-nanoparticle.

Kidney diseases are complicated and can be fatal. Dialysis and transplantation are the only survival solutions to the patients suffering from kidney failures. Both hemodialysis and peritoneal dialysis are risky, due to the possibility of infection and these are expensive and time consuming.

Novel hexapeptide interacts with tubulin and microtubules, inhibits Aβ fibrillation, and shows significant neuroprotection.

Herein, we report a novel hexapeptide, derived from activity dependent neuroprotective protein (ADNP), that spontaneously self-assembles to form antiparallel β-sheet structure and produces nanovesicles under physiological conditions. This peptide not only strongly binds with β-tubulin in the taxol binding site but also binds with the microtubule lattice in vitro as well as in intracellular microtubule networks. Interestingly, it shows inhibition of amyloid fibril formation upon co-incubation with Aβ peptide following an interesting mechanistic pathway and excellent neuroprotection in PC12 cells treated with anti-nerve growth factor (NGF).