Pharmacokinetics, antitumor and cardioprotective effects of liposome-encapsulated phenylaminoethyl selenide in human prostate cancer rodent models.

Purpose: Cardiotoxicity associated with the use of doxorubicin (DOX), and other chemotherapeutics, limits their clinical potential. This study determined the pharmacokinetics and antitumor and cardioprotective activity of free and liposome encapsulated phenyl-2-aminoethyl-selenide (PAESe).

Methods: The pharmacokinetics of free PAESe and PAESe encapsulated in liposomes (SSL-PAESe) were determined in rats using liquid chromatography tandem mass-spectrometry.

Inhibition of JNK and p38 MAPK phosphorylation by 5-(acetylamino)-4-oxo-6-phenyl-2-hexenoic acid methyl ester and 4-phenyl-butenoic acid decreases substance P-induced TNF-α upregulation in macrophages.

The interactions between the immune and nervous systems play an important role in immune and inflammatory conditions. Substance P (SP), the undecapeptide RPKPQQFFGLM-NH2, is known to upregulate the production of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α. We report here that 5-(acetylamino)-4-oxo-6-phenyl-2-hexenoic acid methyl ester (AOPHA-Me) and 4-phenyl-3-butenoic acid (PBA), two anti-inflammatory compounds developed in our laboratory, reduce SP-stimulated TNF-α expression in RAW 264.

Cellular antioxidant activity of phenylaminoethyl selenides as monitored by chemiluminescence of peroxalate nanoparticles and by reduction of lipopolysaccharide-induced oxidative stress.

Hydrogen peroxide (H2O2), produced in living cells by oxidases and by other biochemical reactions, plays an important role in cellular processes such as signaling and cell cycle progression. Nevertheless, H2O2 and other reactive oxygen species are capable of inducing damage to DNA and other cellular components, and oxidative stress caused by overproduction of cellular oxidants has been linked to pathologies such as inflammatory diseases and cancer. Therefore, new approaches for reducing the accumulation of cellular oxidants are of considerable interest from both a biotechnological and a therapeutic perspective.

Myo-inositol hexakisphosphate, isolated from female gametophyte tissue of loblolly pine, inhibits growth of early-stage somatic embryos.

• Myo-inositol hexakisphosphate (InsP(6)), abundant in animals and plants, is well known for its anticancer activity. However, many aspects of InsP(6) function in plants remain undefined. We now report the first evidence that InsP(6) can inhibit cellular proliferation in plants under growth conditions where phosphorus is not limited.

The antioxidant phenylaminoethyl selenide reduces doxorubicin-induced cardiotoxicity in a xenograft model of human prostate cancer.

Anthracyclines are potent anticancer agents, but cardiotoxicity mediated by free radical generation limits their clinical use. This study evaluated the anticancer activity of phenyl-2-aminoethyl selenide (PAESe) and its potential to reduce doxorubicin (DOX)-induced cardiotoxicity. Growth inhibitory effects of PAESe with DOX, and vincristine, clinically used anticancer agents, and tert-butylhydroperoxide (TBHP), a known oxidant, on the growth of human prostate carcinoma (PC-3) cells was determined.

Identification of a thioselenurane intermediate in the reaction between phenylaminoalkyl selenoxides and glutathione.

Selenium has a long history of association with human health and disease, and a low concentration of selenium in plasma has been identified in epidemiological studies as a risk factor for several disorders associated with oxidative stress. This association suggests that organoselenium compounds capable of propagating a selenium redox cycle might supplement natural cellular defenses against oxidants, such as peroxynitrite and hydrogen peroxide. While several such organoselenium compounds are under active investigation as potential therapeutic agents, chemical characterization of reaction intermediates involved in their redox cycling has been problematical.

L-Phenylalanine concentration in blood of phenylketonuria patients: a modified enzyme colorimetric assay compared with amino acid analysis, tandem mass spectrometry, and HPLC methods.

Background: Phenylketonuria (PKU) is an autosomal recessive disorder caused by an impaired conversion of L-phenylalanine (Phe) to L-tyrosine, typically resulting from a deficiency in activity of a hepatic and renal enzyme L-phenylalanine hydroxylase. The disease is characterized by an increased concentration of Phe and its metabolites in body fluids.

Methods: A modified assay based on an enzymatic-colorimetric methodology was developed for measuring blood Phe levels in PKU patients; this method is designed for use with undeproteinized samples and avoids the use of solvents or amphiphilic agents.

Isolation and characterization of a molecule stimulatory to growth of somatic embryos from early stage female gametophyte tissue of loblolly pine.

Loblolly pine (LP, Pinus taeda) is the primary commercial species in southern forests of the US. Somatic embryogenesis (SE) is an effective technique to implement clonal tree production of high-value genotypes from breeding and genetic engineering programs. Unlike angiosperm embryos with attached cotyledons as seed storage organs, the diploid conifer embryo is surrounded by the unattached haploid female gametophyte (FG).