BACKGROUND Urocortin (UCN) gene expression and synthesis have been reported in epithelial and stromal cells of the human endometrium. In this study we evaluated (i) UCN messenger RNA (mRNA) expression and peptide production in uterine specimens collected throughout the endometrial cycle, (ii) UCN secretion after decidualization of cultured human endometrial stromal cells (HESCs) and (iii) the e...

7-Hydroxystaurosporine (UCN-01) is a protein kinase inhibitor that is under development as an anticancer agent in the United States and Japan. Long-term exposure of human A549 non-small cell lung cancer cells to UCN-01 furnished cells (A549/UCN) with acquired resistance against UCN-01. In this study, the sensitivity of these cells toward the growth-arresting properties of certain conventional c...

BACKGROUND UCN-01, a Chk1 inhibitor, abrogates S and G(2) arrest and enhances cancer cell killing by DNA-damaging drugs in preclinical models. UCN-01 avidly binds alpha1-acid glycoprotein in plasma; whether sufficient drug concentrations are achieved in human tumors is unknown. A phase I trial tested the hypothesis that UCN-01 abrogates cisplatin-induced cell cycle arrest (in tumors) at tolerab...

The intermediate portion of the lateral septum (LSi) contains high levels of urocortin (UCN) peptide and type 2 corticotropin-releasing hormone (CRH) receptor (CRHR2) and has anatomic and functional connections with the lateral hypothalamus (LH). We tested the effect of UCN in the LSi on feeding. Injection of 10 or 30 pmol UCN into LSi significantly decreased feeding in food-deprived rats for 2...

A new inhibitor of protein kinase C (PKC), UCN-01, was isolated from the culture broth of Streptomyces sp. N-126. We have found that this strain also produces UCN-02 which is a stereoisomer of UCN-01. The inhibitors have the molecular formula C28H26N4O4 and have an indolo[2,3-alpha]carbazole chromophore. Their structures have been elucidated by mass and NMR spectra. UCN-01 has been shown to inh...

Urocortin (UCN) is a 40-amino acid neuropeptide sharing 45% sequence homology with corticotropin-releasing factor (CRF). The human endometrium expresses both UCN and CRF, and CRF/UCN receptors type-1 (CRF-R1) and -2 (CRF-R2). CRF-R1 activation inhibits cell growth and proliferation of a tumor cell line derived from the human endometrium, and the UCN signaling pathway has been implicated in tumo...

Peptides encoded by the Urocortin (Ucn) II gene, also known as stresscopin-related peptide, were recently identified as new members of the corticotropin-releasing factor (CRF) family. Ucn II is a specific ligand for the type 2 CRF receptor (CRFR). We have demonstrated the peripheral distribution of mouse Ucn (mUcn) II transcripts by using specific mUcn II ribonuclease protection assays, RT-PCR,...

UCN-01 is a derivative of staurosporine, initially developed as a potentially selective inhibitor of the Ca(2+)- and phospholipid-dependent protein kinase C, but with the capacity to inhibit a number of tyrosine and serine/threonine kinases. UCN-01 inhibits the growth of 5 breast carcinoma cell lines with a 50% inhibitory concentration range of 30-100 nM during 6 days of continuous exposure. In...

Although it is known that urocortin 1 (UCN) acts on both corticotropin-releasing factor receptors (CRF(1) and CRF(2)), the mechanisms underlying UCN-induced anorexia remain unclear. In contrast, ghrelin, the endogenous ligand for the growth hormone secretagogue receptor, stimulates food intake. In the present study, we examined the effects of CRF(1) and CRF(2) receptor antagonists (CRF(1)a and ...

Protein kinase C (PKC) is an important constituent of the signaling pathways involved in apoptosis. The PKC inhibitor staurosporine induces apoptosis in many cell types. We characterized the role of PKC in the induction of apoptosis in immature rat thymocytes by investigating the effects of staurosporine with those of five analogs. Four of them, the indolocarbazoles CGP 41251 and UCN-01 and the...