Preclinical drug metabolism and pharmacokinetics of salinomycin, a potential candidate for targeting human cancer stem cells.

There has been a search for new anticancer agents to treat cancer resistance throughout the globe. Salinomycin (SAL), a broad spectrum antibiotic and a coccidiostat has been found to counter tumour resistance and kill cancer stem cells with better efficacy than the existing chemotherapeutic agents; paclitaxel and doxorubicin. This refocused its importance for treatment of human cancers.

Lack of Wdr13 gene in mice leads to enhanced pancreatic beta cell proliferation, hyperinsulinemia and mild obesity.

WD-repeat proteins are very diverse, yet these are structurally related proteins that participate in a wide range of cellular functions. WDR13, a member of this family, is conserved from fishes to humans and localizes into the nucleus. To understand the in vivo function(s) of Wdr13 gene, we have created and characterized a mutant mouse strain lacking this gene.

Antidiabetic activity of resveratrol, a known SIRT1 activator in a genetic model for type-2 diabetes.

In the present study, resveratrol, a polyphenolic SIRT1 activator was evaluated for its SIRT1 activation in an in vitro fluorescent based assay (EC(50) : 7 μM). The efficacy of resveratrol was also evaluated in ob/ob mice for its antidiabetic and associated metabolic effects. Mice aged 5-8 weeks were included in four groups; control and resveratrol at 5, 15, 50 mg/kg, b.

Complex actions of thyroid hormone receptor antagonist NH-3 on gene promoters in different cell lines.

It is desirable to obtain new antagonists for thyroid hormone receptors (TRs) and other nuclear receptors (NRs). We previously used X-ray structural models of TR ligand binding domains (LBDs) to design compounds, such as NH-3, that impair coactivator binding to activation function 2 (AF-2) and block thyroid hormone (triiodothyronine, T(3)) actions. However, TRs bind DNA and are transcriptionally active without ligand.

Amino terminal, but not the carboxy terminal, sequences of tropomyosin-1 are essential for the induction of stress fiber assembly in neoplastic cells.

The presence of aberrant cytoskeleton, arising from the downregulation of key cytoskeletal proteins such as tropomyosins (TMs), is a prominent feature of many malignant cells and is suggested to promote neoplastic growth. While our previous work demonstrated that tropomyosin-1 (TM1) promotes stress fiber assembly and suppresses malignant growth, the molecular basis of the anti-oncogenic effects of TM1 has not been determined. By employing chimeric TMs, here we demonstrate that the amino terminal portion of TM1, but not the carboxy terminal portion which contains the alternatively spliced exon-coded sequences, is essential for stress fiber assembly and suppression of malignant growth.

A mouse gene encoding a novel member of the WD family of proteins is highly conserved and predominantly expressed in the testis (Wdr13).

Wdr13, a novel member of the WD family of proteins and the mouse homolog of WDR13 is localized to the locus XA1.1 and is predominantly expressed in the testis. The expression begins at the early stages of gonadal development and is maintained throughout the adult life with a predominant expression in the germ cells of adult testis.

Crosstalk between CARM1 methylation and CBP acetylation on histone H3.

Background: Dynamic changes in the modification pattern of histones, such as acetylation, phosphorylation, methylation, and ubiquitination, are thought to provide a code for the correct regulation of gene expression mostly by affecting chromatin structure and interactions of non-histone regulatory factors with chromatin. Recent studies have suggested the existence of an interplay between histone modifications during transcription. The CBP/p300 acetylase and the CARM1 methyltransferase can positively regulate the expression of estrogen-responsive genes, but the existence of a crosstalk between lysine acetylation and arginine methylation on chromatin has not yet been established in vivo.