Anti-Androgenic Activity of Icarisid II from Epimedium Herb in Prostate Cancer LNCaP Cells.

Anti-androgens are regarded as potential therapeutic agents for the treatment of prostate cancer. We determined that an epimedium herb (EH) extract exhibited anti-androgenic activity in a luciferase assay using androgen receptor-positive prostate cancer LNCaP cells. Nine EH-derived flavonoids were examined.

Effects of 14 frequently used drugs on prostate-specific antigen expression in prostate cancer LNCaP cells.

Prostate cancer occurs more frequently among older males and such elderly individuals often have chronic underlying disorders for which various drugs are administered for treatment. The levels of prostate-specific antigen (PSA), a widely used prostate cancer marker, are influenced by a number of drugs, such as non-steroidal anti-inflammatory drugs and statins. In the present study, the drugs prescribed to patients on a repeat prescription collected at the pharmacy of the Gifu Pharmaceutical University (Gifu, Japan) were examined for their effects on the levels of PSA expression in prostate cancer LNCaP cells.

Suppression of metallothionein 3 gene expression by androgen in LNCaP prostate cancer cells.

Androgen deprivation therapy is the standard treatment for prostate cancer. However, tumors often progress towards a more aggressive phenotype despite treatment. Prostate tissue has a high zinc concentration, which may correlate with prostate cancer progression.

Anti-androgenic activity of hydroxyxanthones in prostate cancer LNCaP cells.

Anti-androgens are used to treat prostate cancer. Here, we report that hydroxyxanthones from a plant extract act as anti-androgens in androgen receptor (AR)-positive prostate cancer LNCaP cells. Anti-androgenic activity of the ethanol extract from Garcinia subelliptica was observed in a luciferase assay using LNCaP/MMTV cells with a stably integrated mouse mammary tumor virus (MMTV) promoter.

Characterization of the low pH/low nutrient-resistant LNCaP cell subline LNCaP-F10.

Intratumoral regions of low extracellular pH and low nutrition are common features of solid tumors. Although cancer cells normally die when they are removed from their environment, a small population of cells survive. In the present study, the subline LNCaP-F10, of the prostate cancer cell line LNCaP, was isolated and its low pH/low nutrient-resistant properties were examined.

Antiandrogenic activity of resveratrol analogs in prostate cancer LNCaP cells.

The suppression of androgen signaling is a therapeutic target for the treatment of prostate cancer. Resveratrol (3,4',5-trihydroxystilbene) is known to inhibit the function of the androgen receptor (AR). In the present study, we investigated the antiandrogenic activities of resveratrol analogs in order to identify a potent antiandrogen compound.

Low androgen sensitivity is associated with low levels of Akt phosphorylation in LNCaP-E9 cells.

We previously characterized LNCaP-E9, a low-androgen-sensitive LNCaP cell subline. LNCaP-E9 cells exhibit lower expression of androgen-regulated genes, including prostate-specific antigen (PSA), FK506 binding protein 5 (FKBP5), and prostatic acid phosphatase (PAcP), compared with LNCaP cells after treatment with the synthetic androgen R1881, confirming that the cells have low sensitivity to androgens. To understand the mechanism underlying low androgen sensitivity of LNCaP-E9 cells, we examined the activities of the Akt, p44/42, and p38 mitogen-activated protein kinase signaling pathways, all of which are known to be linked to androgen receptor signaling.

AMP-activated protein kinase modulates the gene expression of aquaporin 9 via forkhead box a2.

Aquaporin 9 (AQP9) is permeable to glycerol, which is a source material in lipogenesis and gluconeogenesis in the liver. We investigated the transcriptional regulation of the AQP9 gene by AMP-activated protein kinase (AMPK), known as an energy sensor in cells since AMPK contributes to the metabolism of carbohydrate, lipid, and protein by regulating the expression of many enzymes and transcription factors in metabolic pathways. An AMPK activator, 5-aminoimidazole-4-carboxamide-1-β-d-ribonucleoside (AICAR), was observed to suppress the expression of the AQP9 gene in HepG2 cells by promoting the phosphorylation of AMPK and AKT/PKB.

Androgen receptor W741C and T877A mutations in AIDL cells, an androgen-independent subline of prostate cancer LNCaP cells.

The androgen-independent LNCaP (AIDL) cell line was generated by maintaining prostate cancer LNCaP cells in a hormone-deprived medium. Notably, synthetic androgen R1881-related gene response is attenuated in AIDL cells as compared to the parental LNCaP cells. The aim of this study was to clarify the mechanisms underlying androgen sensitivity in AIDL cells.

Castration- and aging-induced changes in the expression of zinc transporter and metallothionein in rat prostate.

Prostate tissue contains high concentrations of zinc. Zinc content in the prostate gland changes in prostatic disease, such as benign prostate hyperplasia and prostate cancer, which occur more frequently with increasing age. Prostate zinc content is also known to decrease after castration in animal models.

Up-regulation of the lysyl hydroxylase 2 gene by acetaminophen and isoniazid is modulated by transcription factor c-Myb.

Objectives: Lysyl hydroxylase 2 (LH2), an isoform of hydroxylase, catalyses the hydroxylation of lysine residues in the telopeptide of collagen to form stable and irreversible cross-linkages in collagen. Increased activity of this enzyme in activated stellate cells in human liver has been proposed to relate to the promotion of hepatic fibrosis. In the present study, we examined the regulation of LH2 expression in drug-induced liver injury in order to clarify the mechanisms behind the hepatic fibrosis caused by certain drugs.

Pamidronate inhibits antiapoptotic bcl-2 expression through inhibition of the mevalonate pathway in prostate cancer PC-3 cells.

Bisphosphonates are expected to be efficacious to prevent the growth of metastatic cancer in bone tissue. Bone metastases often occur in patients with various cancers, such as breast, lung and prostate cancer. Bcl-2 is a potent antiapoptotic protein and its expression is known to be closely related to its function.

Protein kinase C is inhibited by bisphosphonates in prostate cancer PC-3 cells.

Bisphosphonates are expected to be effective at preventing tumor metastasis to bone tissue. Since protein kinase C (PKC) plays a crucial role in cancer progression, we examined the effect of bisphosphonates on PKC expression to clarify the mechanism behind the inhibition of the bone metastasis of prostate cancer by bisphosphonates. We found that pamidronate inhibits PKC protein expression and PKC activity in prostate cancer PC-3 cells.

Preparation of a fast dissolving oral thin film containing dexamethasone: a possible application to antiemesis during cancer chemotherapy.

We prepared fast dissolving oral thin film that contains dexamethasone and base materials, including microcrystalline cellulose, polyethylene glycol, hydroxypropylmethyl cellulose, polysorbate 80 and low-substituted hydroxypropyl cellulose. This preparation showed excellent uniformity and stability, when stored at 40 degrees C and 75% in humidity for up to 24 weeks. The film was disintegrated within 15s after immersion into distilled water.

Regulation of glyceraldehyde 3-phosphate dehydrogenase expression by metformin in HepG2 cells.

Biguanides are known to have a serious side effect, lactic acidosis. We previously reported that buformin suppressed the expression of glyceraldehyde 3-phosphate dehydrogenase (GAPD) and suggested that this decrease was one of the causes of lactic acidosis. In this study, we examined the signaling pathway and regulatory factors for the expression of the GAPD gene triggered by metformin in HepG2 cells.

Overexpression of thymosin beta4 increases pseudopodia formation in LNCaP prostate cancer cells.

Thymosin beta4, a major G-actin-sequestering protein, is known to be involved in tumor metastasis. In the present study, we found that thymosin beta4 expression promotes the formation of actin-based pseudopodia-like extensions, associated with cell migration, in human prostate cancer LNCaP cells. Treatment with the phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin and Cdc42/Rac1/RhoA inhibitor Clostridium difficile toxin B significantly reduced pseudopodia formation in thymosin beta4-overexpressing LNCaP cells, suggesting that the pseudopodia formation by thymosin beta4 is probably involved in PI3K and Rho family pathway.

A comparative investigation of fetal skeletal anomalies in rats induced by acetylsalicylic acid with single- and double-staining techniques.

Acetylsalicylic acid (ASA) at single doses of 125, 250, and 500mg/kg was administered to pregnant rats on Gestation Day (GD) 10, and skeletal changes in fetuses harvested on GD 20 and pups on post-natal (PN) Day 21 were evaluated. Changes in cartilage and ossified bones identified by Alizarin Red S single-staining were compared with Alizarin Red S and Alcian Blue double-staining. By the single-staining technique, skeletal abnormalities including fused rib, incomplete ossification of the cervical arch, absent/hemicentric body of thoracic or lumbar vertebra, deformation of lumbar arch, and absent sacral arch were demonstrated in at 250 and 500mg/kg ASA on GD 20.

Evidence that androgen-independent stromal growth factor signals promote androgen-insensitive prostate cancer cell growth in vivo.

Activation of tumor-stromal interactions is considered to play a critical role in the promotion of tumorigenesis. To discover new therapeutic targets for hormone-refractory prostate tumor growth under androgen ablation therapy, androgen-sensitive LNCaP cells and the derived sublines, E9 (androgen-low-sensitive), and AIDL (androgen-insensitive), were recombined with androgen-dependent embryonic rat urogenital sinus mesenchyme (UGM). Tumors of E9 + UGM and AIDL + UGM were approximately three times as large as those of LNCaP + UGM.

Preventive effect of co-administration of water containing magnesium ion on indomethacin induced lesions of gastric mucosa in adjuvant-induced arthritis rat.

It is well known that nonsteroidal anti-inflammatory drugs (NSAIDs) have significant side effects, such as gastroenteropathy, and that rheumatoid arthritis patients taking NSAIDs are more susceptible to NSAIDs-induced gastric lesions as compared with patients with other diseases. We demonstrate the preventive effect of the co-administration of bittern water (BW, nigari-sui in Japanese), which enables the effective intake of Mg(2+), on the ulcerogenic response to indomethacin in adjuvant-induced arthritis (AA) rats. Four kinds of BW with different Mg(2+) contents; ranging from 10-200 mg/l Mg(2+) (BW-10, 25, 50, 200) were used in this study.

Involvement of interleukin 18 in indomethacin-induced lesions of the gastric mucosa in adjuvant-induced arthritis rat.

It is well known that nonsteroidal anti-inflammatory drugs (NSAIDs) have significant side effects, such as gastroenteropathy, and rheumatoid arthritis patients taking NSAIDs are more susceptible to NSAIDs-induced gastric lesions in comparison with other patients. The pathogenic mechanism of these lesions is not fully understood. We demonstrate whether interleukin 18 (IL-18) expression relate the aggravation of gastric lesion in adjuvant-induced arthritis (AA) rats following the oral administration of indomethacin.

Comparison of the mechanisms of cataract development involving differences in Ca2+ regulation in lenses among three hereditary cataract model rats.

We previously found that the increases in Ca2+ content in the lenses of three hereditary cataract model rats, UPL rat (UPLR), Shumiya cataract rat (SCR) and Ihara cataract rat (ICR), are inhibited by aminoguanidine, a selective inhibitor of inducible nitric oxide synthase, and that the mechanisms of Ca2+ enhancement in these rat models differ. In this study, we compare the mechanisms for dysfunction in Ca2+ regulation in UPLR, SCR and ICR. Decreases in the activity of Ca2+-ATPase were found in the lenses of SCR and ICR concurrent with cataract development.

Simultaneous determination of benzodiazepines and their metabolites in human serum by liquid chromatography-tandem mass spectrometry using a high-resolution octadecyl silica column compatible with aqueous compounds.

A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method using a high-resolution octadecyl silica column compatible with aqueous compounds was developed for the simultaneous determination of benzodiazepines and their metabolites in human serum. This method enabled us to determine multiple benzodiazepines, including flurazepam, bromazepam, chlordiazepoxide, nitrazepam, clonazepam, flunitrazepam, estazolam, clobazam, lorazepam, alprazolam, triazolam, brotizolam, fludiazepam, diazepam, quazepam, prazepam and their metabolites such as 7-aminonitrazepam, 7-aminoclonazepam, 7-acetamidonitrazepam, N-desmethylclobazam and N-desmethyldiazepam. The analytes spiked into human serum were subjected to solid-phase extraction followed by liquid chromatography coupled with electrospray ionization tandem mass spectrometry.

Membrane trafficking of aquaporin 3 induced by epinephrine.

We investigated the membrane trafficking of AQP3 induced by epinephrine in Caco-2 cells to clarify the digestive absorption of glycerol permeated by AQP3. Epinephrine was found to promote within 60 min the translocation of AQP3 from the cytoplasmic fraction to the plasma membrane. This increased trafficking of AQP3 was suppressed by phospholipase C and protein kinase C (PKC) inhibitors and a phorbol ester accelerated the trafficking of AQP3 to the membrane fraction.

Regulation of aquaporin 3 expression by magnesium ion.

For understanding the actions of magnesium formulations, magnesium oxide and magnesium sulfate as a constituent of antacid, in the gastrointestinal tract, the effect of magnesium ion on the water channel aquaporin 3 (AQP3) known to be permeable mainly to water and glycerol was investigated in Caco-2 cells. The mRNA and protein of aquaporin 3 were detected by real-time RT-PCR and Western blotting, respectively, and found to increase significantly after treatment with magnesium acetate. Inhibitors for signal transducers, MDL-12330A, H-89, U0126, and Ro 31-8220, were shown to repress the increase in expression of the mRNA.

Pamidronate down-regulates urokinase-type plasminogen activator expression in PC-3 prostate cancer cells.

Background: Bisphosphonates are considered to be effective in preventing tumor metastasis to bone. Urokinase-type plasminogen activator (uPA) is thought to be critically involved in the metastatic phenotype of prostate cancer. In this study, we examined the effect of pamidronate on uPA expression in PC-3 prostate cancer cells.