Glycogen synthase kinase-3beta (GSK-3beta) is a ubiquitously expressed constitutively active serine/threonine kinase that phosphorylates cellular substrates and thereby regulates a wide variety of cellular functions, including development, metabolism, gene transcription, protein translation, cytoskeletal organization, cell cycle regulation, and apoptosis. The activity of GSK-3beta is negatively...

Ultraviolet B (UVB)-induced cyclooxygenase-2 (COX-2) expression plays an important role in UVB tumor promotion. We examined whether Akt and glycogen synthase kinase 3beta (GSK-3beta), components of the phosphatidylinositol 3'-kinase pathway, are involved in UVB induction of COX-2 transcription. UVB caused Akt phosphorylation at both Thr-308 and Ser-473 that was inhibited by LY294002, a phosphat...

The objective of the present study was to investigate the effects of genistein and equol on 3beta-hydroxysteroid dehydrogenase (3beta-HSD) and 17beta-hydroxysteroid dehydrogenase 3 (17beta-HSD3) in human and rat testis microsomes. These enzymes (3beta-HSD and 17beta-HSD3), along with two others (cytochrome P450 side-chain cleavage enzyme and cytochrome P450 17alpha-hydroxylase/17-20 lyase), cat...

BACKGROUND Aberrant regulation of glycogen synthase kinase-3beta (GSK-3beta) has been implicated in several human cancers; however, it has not been reported in the gastric cancer tissues to date. The present study was performed to determine the expression status of active form of GSK-3beta phosphorylated at Tyr216 (pGSK-3beta) and its relationship with other tumor-associated proteins in human g...

Prostate cancer is a major health threat for American men. Therefore, the development of effective therapeutic options is an urgent issue for prostate cancer treatment. In this study, we evaluated the effect of glycogen synthase kinase-3beta (GSK-3beta) suppression on tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in human prostate cancer cell lines. In the pr...

There are conflicting reports regarding the effect of dietary cholesterol-oxidation products (oxysterols) on the development of atherosclerosis in experimental animals. To address this issue, apolipoprotein (Apo) E-deficient mice were fed a purified diet (AIN-93) or the same purified diet containing 0.2 g cholesterol or 0.2 g oxysterols/kg. The dietary oxysterols had no significant effect on th...

Syntheses of steroidal heterocycles containing a five-membered N,S- heterocycle attached at the 6,7 positions of the B ring are reported. 5Alpha-cholestane-6-one (1), its 3beta-acetoxy- (2) and 3beta-chloro- (3) analogues reacted with semicarbazide and aqueous sodium acetate in refluxing ethanol to yield 5alpha-cholestan-6-one-semicarbazone 1a and its 3-beta-acetoxy and 3beta-chloro derivatives...

RATIONALE Numerous studies have proposed that glycogen synthase kinase (GSK)-3beta is a central regulator of the hypertrophic response of cardiomyocytes. However, all of this work has relied on overexpression of GSK-3beta, expression of constitutively active mutants, or small molecule inhibitors with documented off-target effects. Genetic loss of function approaches have not been used in the ad...

Wee1 protein kinase plays an important regulatory role in cell cycle progression. It inhibits Cdc-2 activity by phosphorylating Tyr15 and arrests cells at G2-M phase. In an attempt to understand Wee1 regulation during cell cycle, yeast two-hybrid screening was used to identify Wee1-binding protein(s). Five of the eight positive clones identified encode 14-3-3beta. In vivo binding assay in 293 c...

Ambrox (1), a perfumery diterpene, was oxidatively metabolised by a plant pathogenic fungus Botrytis cinerea in a xenobiotic fashion to afford a major product, i.e., 1beta-hydroxy-8-epiambrox (13) (60%) along with three minor metabolites 3beta-hydroxyambrox (2), sclareolide (5) and 3beta-hydroxysclareolide (7). Sclareolide (5), a cytotoxic diterpenoidal lactone was fermented with the same fungu...