Au(iii)-Proline derivatives exhibiting selective antiproliferative activity against HepG2/SB3 apoptosis-resistant cancer cells.

This paper deals with the combination of a proline-based moiety with biologically active gold centers in the oxidation states +1 and +3. In particular, six Au(i)/(iii)-proline dithiocarbamato (DTC) complexes with general formulae [Au(DTC)2] and [AuIIIX2(DTC)] (X = Cl, Br) are reported here. After the synthesis of the ligand and the complexes, all derivatives were characterized via several techniques and tested for their stability in DMSO/water media. This study was focused on the demonstration of a peculiar behavior of Au(iii)-DTC species in solution. Finally, the complexes were screened for their antiproliferative activity against 2 human cancer cell lines, namely HepG2 and HepG2/SB3, taken as models of hepatocellular carcinoma. The latter, chosen for its aggressiveness due to the upregulation of the anti-apoptotic protein SerpinB3, was selectively inhibited in terms of growth by some Au(iii)-DTC complexes.

Synthesis, chemical characterization and cancer cell growth-inhibitory activities of Cu(ii) and Ru(iii) aliphatic and aromatic dithiocarbamato complexes.

In this paper, we focused on the analysis of the effects mediated by different cyclic dithiocarbamic ligands (DTC) on three classes of antiproliferative coordination compounds, namely, Ru(iii) complexes with the general formulae [Ru(DTC)3] and [Ru2(DTC)5]Cl, and the neutral Cu(ii) derivatives of the type [Cu(DTC)2]. In particular, we present the synthesis and characterization of a library of total 23 coordination compounds containing Ru(iii) or Cu(ii) as the biologically-active metal center and two or more dithiocarbamato (DTC) ligands derived from cyclic amines (aliphatic or aromatic). Several techniques including elemental analysis, X-ray crystallography, ESI-MS, 1H-NMR spectroscopy, FT-IR and UV-Vis spectrophotometry were used to characterize the compounds, which highlighted the different electronic behaviors generated by the substituents within the DTC moiety. Moreover, the synthesized compounds were tested for their stability in order to investigate their antiproliferative activity against 3 human cancer cell lines, namely, HeLa, HepG2 and HepG2/SB3. In particular, HepG2/SB3 was chosen for its aggressiveness due to upregulation of the anti-apoptotic protein SerpinB3. Finally, the most promising compounds are studied in terms of log P. Overall, the results reveal the drug-likeness of some of the derivatives of copper(ii) and ruthenium(iii).

Ru(III) anticancer agents with aromatic and non-aromatic dithiocarbamates as ligands: Loading into nanocarriers and preliminary biological studies.

Since the discovery of cisplatin in the 1960s, other metal complexes have been investigated as potential antitumor agents to overcome the side-effects associated with the administration of the Pt-based drug. In line with our previous research, in this work we report the synthesis and characterization of mono- and dinuclear Ru(III) complexes with the pyrrolidinedithiocarbamate (PDT) ligand and the more sterically-hindered carbazole-dithiocarbamato ligand (CDT), to compare their properties (both at the chemical and antiproliferative level), in an attempt to assess a structure-activity rationale. Moreover, to overcome the scarce solubility under physiological conditions of the Ru(III)-dithiocarbamato compounds, the biocompatible copolymer Pluronic® F127 has been used, to encapsulate the metal derivatives in water-soluble micellar carriers. Finally, preliminary biological evaluations on CDT and PDT compounds along with their nanoformulations, open intriguing perspectives in anticancer chemotherapy. In particular, comparing the structure of the Ru(III) derivatives, the ionic dinuclear PDT complex shows an important cytotoxic action in comparison to its neutral counterparts. Moreover, the micellar carrier improves the overall activity of the encapsulated Ru(III)-PDT chemotherapeutics. On the other hand, the nanoformulation of the CDT derivatives allows us to solubilize both the 1:3 and the 2:5 complexes and to state their inactivity.

The Murine Prepuberal Oviduct Supports Early Embryo Development In Vitro: (mouse embryo coculture/2 cell-block/immature oviduct/protein secretion/early embryo signal).

Swiss albino mice were used to evaluate the ability of explanted murine oviducts to support development through the block stage. One cell eggs develop as well when cultured 50 hours in oviducts explanted from pregnant mice or in oviducts from immature mice: The blastocyst formation occurs at a similar rate in both cases. The viability of the blastocysts was high (8/9) when transferred to pseudopregnant (C 57 Black) recipient mice. Only a few difference was observed in the polypeptide pattern of immature and pregnant explanted oviduct. In immature oviduct, the polypeptide secretory profile is not modified by the presence of fertilized embryos transferred into it, and so nor is it directly egg dependent. It is concluded that oviduct's ability to sustain normal early embryonic developments is not dependent upon sexual maturity.

Characteristics and development of the tyrosine-rich protein granules in the adipose tissue of the Curculionid beetle Sitophilus oryzae.

In the Curculionid beetle Sitophilus oryzae, the fat body is composed of one type of adipocyte, interstitial cells and oenocytes. Synthesis and storage of tyrosine-rich-protein granules (TRPG) in adipocytes are observed during all the larval and prepupal stages (except the first larval instar which has not been studied). They appear first in the posterior part of the fat body, around the nucleus of adipocytes. They progressively invade the cytoplasm. In the young pupa, TRPG are present in every part of the body, including the head and the appendages in formation. TRPG grow in size by fusing together. Their mean diameter is 6 microm, but some of them reach up to 50 microm. They present a basic core and an acidic periphery. Their charge in tyrosine increases until the prepupa. They are APS and lipid negative and contain no RNA. During metamorphosis they take on a reticulated structure, evoking a golf ball, and disintegrate into small granules, the tyrosine content of which diminishes drastically, especially in contact with epidermal cells, whence tyrosine is probably transferred. TRPG in S. oryzae contain 16 different insoluble proteins. Five of them are tyrostaurins characterized by their very high content in tyrosine (up to 27%) and their strict insolubility in aqueous solution. Arylphorin-like proteins have not been detected in S. oryzae granules.

Is genome size influenced by colonization of new environments in dipteran species?

Genome size differences are usually attributed to the amplification and deletion of various repeated DNA sequences, including transposable elements (TEs). Because environmental changes may promote modifications in the amount of these repeated sequences, it has been postulated that when a species colonizes new environments this could be followed by an increase in its genome size. We tested this hypothesis by estimating the genome size of geographically distinct populations of Drosophila ananassae, Drosophila malerkotliana, Drosophila melanogaster, Drosophila simulans, Drosophila subobscura, and Zaprionus indianus, all of which have known colonization capacities. There was no strong statistical differences between continents for most species. However, we found that populations of D. melanogaster from east Africa have smaller genomes than more recent populations. For species in which colonization is a recent event, the differences between genome sizes do not thus seem to be related to colonization history. These findings suggest either that genome size is seldom modified in a significant way during colonization or that it takes time for genome size of invading species to change significantly.

Changes in ecdysteroid and juvenile hormone titers in the hemolymph of Galleria mellonella larvae and pupae.

The variations in circulating ecdysteroids and juvenile hormones (JH) in Galleria, from the end of the antepenultimate larval stage until emergence of adults, have been determined. The two hormonal families were extracted separately from the same hemolymph sample and quantified by two radioimmunoassays. Juvenile hormone RIA activity was about 35 nM in larvae of the antepenultimate and penultimate stages. It dropped before each molt and increased thereafter. Moreover, it gradually decreased during the last larval instar. In pupae, it was generally low, but it rose drastically during the late pupal development and in young adults. This rise was very much higher in females than in males. Three different RIA-active compounds were found; they were assumed to be JH-I, JH-II, and JH-III according to their retention times in HPLC. The three compounds were present in almost equal concentration in larvae of the penultimate stage: JH-I predominated, however, during the last larval instar. In late pupae, the main hormone was JH-III both in males and in females. There is no clear relationship between ecdysteroid and juvenile hormone changes, except for a female-specific ecdysteroid rise which coincides with the juvenile hormone release in late pupae. This double hormonal stimulation can be involved in the regulation of vitellogenin synthesis and deposition in oocytes.

A molecular aspect of symbiotic interactions between the weevil Sitophilus oryzae and its endosymbiotic bacteria: over-expression of a chaperonin.

Specific proteins of symbiosis were analyzed by the comparison of two-dimensional electrophoresis protein patterns of symbiotic and aposymbiotic strains of the weevil Sitophilus oryzae. One protein was shown to be exclusively expressed in the aposymbiotic strain and three proteins, including a chaperonin, were characterized in the symbiotic strain pattern. The groE-like operon, encoding the two chaperonins groES and GroEL-like proteins of the endocytobiotes, was sequenced. It was found to be very similar to the groE operon of Escherichia coli (82% identity). In vitro and ex vivo experiments of protein labelling demonstrated that almost 40% of the endocytobiote protein synthesis ex vivo is focused on the GroEL-like protein. Finally, we showed by northern blotting that heat shock at 38 degrees C results in groEL mRNA accumulation inside the endocytobiotes. This work supports the hypothesis that chaperonins could have an essential physiological function in the maintenance of the symbiotic association.