Synthesis and structure of mono-, bi- and trimetallic amine-bis(phenolate) cobalt(II) complexes

A series of cobalt(II) amine-bis(phenolate) complexes has been prepared and characterized. The protonated tripodal tetradentate ligand precursors; dimethylaminoethylamino-N,N-bis(2-methylene-4-tert-butyl-6-methylphenol), H2[O2NN¢]BuMeNMe2, dimethylaminoethylamino-N,N-bis(2-methylene-4,6-di-tert-butylphenol), H2[O2NN¢]BuBuNMe2, diethylaminoethylamino-N,N-bis(2-methylene-4,6-di-tert-amylphenol), H2[O2NN¢]AmAmNEt2 and 2-pyridylamino-N,N-bis(2-methylene-4,6-di-tert-amylphenol), H2[O2NN¢]AmAmPy; were reacted with cobaltous acetate tetrahydrate under varying conditions to afford a range of monometallic, bimetallic and trimetallic species. An unusual four coordinate complex Co[O2NN¢]AmAmNEt2 containing CoII in a trigonal monopyramidal environment was structurally characterized, whereas using a less sterically demanding ligand a series of five coordinate complexes Co[O2NN¢]BuBuNMe2(L) (L = H2O, CH3OH, (CH3)2C=O, propylene oxide) containing CoII in a trigonal bipyramidal environment was prepared. A new angular structural parameter related to t is defined, where t¢ may be used to compare complexes with trigonal monopyramidal structures. In contrast, ligands containing a pendant pyridyl donor afford dimeric species including {Co(m-CH3OH)[O2NN¢]AmAmPy}2. In the absence of base and in the presence of excess cobaltous acetate, trimetallic complexes were isolated containing a central CoII in an octahedral environment coordinated to four CH3OH and two bridging acetate ligands between two Co[O2NN¢] fragments with CoII in a trigonal bipyramidal setting. The paramagnetic CoII complexes reported were also characterized by UV-vis spectroscopy, mass spectrometry, cyclic voltammetry and magnetic measurements

Loss of Protein Kinase C δ Gene Expression in Human Squamous Cell Carcinomas: A Laser Capture Microdissection Study

Protein kinase C delta (PKC-δ) protein levels are frequently low in chemically and UV-induced mouse skin tumors as well as in human cutaneous squamous cell carcinomas (SCCs). Furthermore, overexpression of PKC-δ in human SCC lines and mouse epidermis is sufficient to induce apoptosis and suppress tumorigenicity, making PKC-δ a potential tumor suppressor gene for SCCs. Here we report that PKC-δ is lost in human SCCs at the transcriptional level. We used laser capture microdissection to isolate cells from three normal human epidermis and 14 human SCCs with low PKC-δ protein. Analysis by quantitative reverse transcription-PCR revealed that PKC-δ RNA was reduced an average of 90% in the SCCs tested, consistent with PKC-δ down-regulation at the protein level. Analysis of DNA from nine of the same tumors revealed that PKC-δ gene was deleted in only one tumor. In addition, Ras-transformed human keratinocytes, which have selective down-regulation of PKC-δ at both protein and mRNA levels, had significantly repressed human PKC-δ promoter activity. Together, these results indicate that PKC-δ gene expression is suppressed in human SCCs, probably via transcription repression. Our results have implications for the development of topical therapeutic strategies to trigger the re-expression of pro-apoptotic PKC-δ to induce apoptosis in SCCs

Hypoxia Suppression of Bim and Bmf Blocks Anoikis and Luminal Clearing during Mammary Morphogenesis

Hypoxia can regulate many cellular processes. We show that hypoxia, via hypoxia-inducible factor (HIF)-1, blocks anoikis of epithelial cells by activating signaling pathways that inhibit expression of proapoptotic proteins Bim and Bmf. Hypoxia also disrupts mammary morphogenesis and blocks anoikis associated with lumen formation in three-dimensional in vitro model of mammary acini