Identification of phytoestrogens as sirtuin inhibitor against breast cancer: Multitargeted approach.

Despite progress in diagnosis and treatment strategies, breast cancer remains a primary risk to female health as indicated by second most cancer-deaths globally caused by this cancer. High risk mutation is linked to prognosis of breast cancer. Due to high resistance of breast cancer against current therapies, there is necessity of novel treatment strategies.

Inhibitor of DNA binding/differentiation proteins as IDs for pancreatic cancer: Role in pancreatic cancer initiation, development and prognosis.

A family of inhibitors of cell differentiation or DNA-binding proteins, known as ID proteins (ID1-4), function as mighty transcription factors in various cellular processes, such as inhibiting differentiation, promoting cell-cycle progression, senescence, angiogenesis, tumorigenesis, and metastasis in cancer. Pancreatic cancer represents the deadliest cancer with the lowest survival rate of 10% due to the diagnosis at an advanced fatal stage and therapeutic resistance. Modestly, the only curative option for this lethal cancer is surgery but is done in less than 15-20% of patients because of the locally aggressive and early metastatic nature.

Western blotting: a powerful staple in scientific and biomedical research.

Western blotting (WB), also known as immunoblotting, is a well-known molecular biology method that biologists often use to investigate many features of the protein, ranging from basic protein analysis to disease detection. WB is simple, unique, rapid, widely used routine tool with easy interpretation and definite results. It is being used in various fields of science, research and development, diagnostic labs and hospitals.

Autophagic and apoptotic cell death induced by the quinoline derivative 2-(6-methoxynaphthalen-2-yl)quinolin-4-amine in pancreatic cancer cells is via ER stress and inhibition of Akt/mTOR signaling pathway.

Pancreatic cancer (PC) is among the most lethal cancers and is resistant to existing therapies, which highlights the need for new and alternative therapeutic treatments. Autophagy is emerging as one of the alternative cell death mechanisms and is well known to cross-talk with apoptosis. Autophagy can act as a viable option to treat highly resistant PC.

Click linker: efficient and high yielding synthesis of a new family of kojic acid congeners as cytotoxic agents.

Highly efficient methodology was developed for the construction of functionalized Kojic acid involving Click linker via 1,3-dipolar cycloaddition and their cytotoxicity against MCF-7, MIAPaCa-2 and DU145 mammalian cell lines were evaluated. Preliminary studies on structure-activity-relationship (SAR) revealed that substitution at C-2 of kojic acid as well as C-5 of 1,2,3-triazole motif played a major role in the activity profile. Kojic acid 1,2,3-triazole analogue containing an alkyl chain ( = 6) exhibited two fold potent activity than the parent compound, kojic acid against MCF-7 and MIA PaCa-2 cell lines.

9-Ethynyl noscapine induces G2/M arrest and apoptosis by disrupting tubulin polymerization in cervical cancer.

Noscapine is a phthalide isoquinoline alkaloid present in the latex of Papaver somniferum and has demonstrated potent antitumor activity in various cancer models. Structural changes in the core molecule of noscapine architecture have produced a number of potent analogs. We have recently synthesized the novel noscapine analogs (3, 4, and 5) with different functional groups appended at ninth position of natural noscapine.

Quisinostat mediated autophagy is associated with differentiation in neuroblastoma SK-N-SH cells.

Neuroblastoma (NB) is the most common childhood cancer that arises from the sympathetic nervous system. NB is characterized by poor prognosis. One of the strategies to control NB is activating the differentiation process in undifferentiated NB cells.

Epigenetic modulation and understanding of HDAC inhibitors in cancer therapy.

The role of genetic and epigenetic factors in tumor initiation and progression is well documented. Histone deacetylases (HDACs), histone methyl transferases (HMTs), and DNA methyl transferases. (DNMTs) are the main proteins that are involved in regulating the chromatin conformation.

Fluorinated thiazolidinol drives autophagic cell death in pancreatic cancer cells via AMPK activation and perturbation of critical sentinels of oncogenic signaling.

Pancreatic cancer is one of the most malignant cancers around the world. The co-occurrence of mutation in KRAS and p53 makes it highly aggressive, proliferative, metastatic, and resistant to apoptotic cell death. Therefore, there is a need to trigger an alternate mechanism of cancer cell death in apoptosis-resistant pancreatic cancer.

Cloning and in vivo metabolizing activity study of CYP3A4 on amiodarone drug residues: A possible probiotic and therapeutic option.

Background: Amiodarone represents a principal antiarrhythmic pharmaceutical drug available in the market for the treatment of ventricular arrhythmias. However, despite its better efficacy, the usage of amiodarone is associated with extracardiac toxicity. The human body evolved a system of cytochrome P450 enzymes which play an essential role in the metabolism of harmful foreign substances.

Inhibition of JNJ-26481585-mediated autophagy induces apoptosis via ROS activation and mitochondrial membrane potential disruption in neuroblastoma cells.

Neuroblastoma (NB) is the common pediatric tumor of the sympathetic nervous system characterized by poor prognosis. Owing to the challenges such as high tumor heterogeneity, multidrug resistance, minimal residual disease, etc., there is an immediate need for exploring new therapeutic strategies and effective treatments for NB.

Imidazo[2,1-]thiazole-Coupled Natural Noscapine Derivatives as Anticancer Agents.

Noscapine, a phthalide isoquinoline alkaloid isolated from the opium poppy is traditionally being used as an anticough drug. With a safe in vitro toxicological profile, noscapine and its analogues have been explored to show microtubule-regulating properties and anticancer activity against various mammalian cancer cell lines. Since then, our group and other research groups worldwide are working on developing new noscapinoids to tap its potential as the leading drug molecule.

Antimicrobial and anticancer potential of low molecular weight polypeptides extracted and characterized from leaves of Azadirachta indica.

Low molecular weight antimicrobial polypeptides were extracted and purified from the young fresh leaves of Azadirachta indica (neem). The total protein extracted was precipitated with 15% TCA-Acetone. The total purified proteins yielded from the two extraction methods were 122.

Scriptaid cause histone deacetylase inhibition and cell cycle arrest in HeLa cancer cells: A study on structural and functional aspects.

Scriptaid (SCR), a well-known histone deacetylase inhibitor, cause various cellular effects such as cell growth inhibition and apoptosis. In this study, we have evaluated the anti-cancer effects of Scriptaid in HeLa cells, IMR-32 and HepG2 cells. Scriptaid inhibited the growth of HeLa cells with IC of 2μM at 48h in a dose-dependent manner.

Microtubule Targeting Agents as Cancer Chemotherapeutics: An Overview of Molecular Hybrids as Stabilizing and Destabilizing Agents.

Microtubules form crucial dynamic structural cellular components of the cell and are composed of the alpha beta tubulin heterodimers. Microtubules are involved in a wide variety of functions in the cell such as attribution to cell shape, motility, intracellular trafficking and mitotic spindle formation. Owing to these reasons, tubulin and microtubules have gained significant interest as important targets for cancer therapy.

Evaluating the probiotic and therapeutic potentials of Saccharomyces cerevisiae strain (OBS2) isolated from fermented nectar of toddy palm.

The purpose of this study is to evaluate the probiotic characteristics of 15 yeast strains isolated from nectar of toddy palm. Initially, the collected samples were inoculated on yeast extract peptone dextrose agar plates and the colonies so obtained were culturally and morphologically characterized. Commercial probiotic yeast, Saccharomyces boulardii served as the control in these experiments.

Prohibitin confers cytoprotection against ISO-induced hypertrophy in H9c2 cells via attenuation of oxidative stress and modulation of Akt/Gsk-3β signaling.

Numerous hypertrophic stimuli, including β-adrenergic agonists such as isoproterenol (ISO), result in generation of reactive oxygen species (ROS) and alteration in the mitochondrial membrane potential (Δψ) leading to oxidative stress. This process is well associated with phosphorylation of thymoma viral proto-oncogene Akt (Ser473) and glycogen synthase kinase-3β (Gsk-3β) (Ser9), with resultant inactivation of Gsk-3β. In the present study, we found that the protective defensive role of prohibitin (PHB) against ISO-induced hypertrophic response in rat H9c2 cells is via attenuation of oxidative stress-dependent signaling pathways.

PHB in Cardiovascular and Other Diseases: Present Knowledge and Implications.

Background: Prohibitin (PHB) is overtly conserved evolutionarily and ubiquitously expressed protein with pleiotropic functions in diverse cellular compartments. However, regulation and function of these proteins in different cells, tissues and in various diseases is different as evidenced by expression of these proteins which is found to be reduced in heart diseases, kidney diseases, lung disease, Crohn's disease and ulcerative colitis but this protein is highly expressed in diverse cancers. The mechanism by which this protein acts at the molecular level in different subcellular localizations or in different cells or tissues in different conditions (diseases or normal) has remained poorly understood.

A proteomic view of isoproterenol induced cardiac hypertrophy: prohibitin identified as a potential biomarker in rats.

Background: The present study aimed at using a proteomics based approach to: a) analyze and contrast the proteome of the healthy and isoproterenol induced hypertrophied hearts and b) identify potential biomarkers for diagnosis of cardiac hypertrophy.

Methods: Male Sprague Dawley (SD) rats were administered isoproterenol (ISO, 5 mg/kg, sc, once daily) for 14 days to induce cardiac hypertrophy. There was a significant (p<0.