Recent progress in genetics of aging, senescence and longevity: focusing on cancer-related genes.

It is widely believed that aging results from the accumulation of molecular damage, including damage of DNA and mitochondria and accumulation of molecular garbage both inside and outside of the cell. Recently, this paradigm is being replaced by the "hyperfunction theory", which postulates that aging is caused by activation of signal transduction pathways such as TOR (Target of Rapamycin). These pathways consist of different enzymes, mostly kinases, but also phosphatases, deacetylases, GTPases, and some other molecules that cause overactivation of normal cellular functions.

Integrin α5β1 simultaneously controls EGFR-dependent proliferation and Akt-dependent pro-survival signaling in epidermoid carcinoma cells.

To delineate distinctive role of the components of α5β1 integrin-EGFR axis in control of epidermoid carcinoma cell proliferation, we performed individual inhibition of α5β1 and EGFR via genetic and phamacological methods, respectively. We demonstrated that pharmacological inhibition of epidermal growth factor receptor (EGFR) significantly affected proliferation of A431 human cells by inducing the G0/G1 cell cycle arrest, whereas shRNA-mediated depletion of α5 subunit of α5β1 integrin led to a similar type of cell cycle arrest followed by significant apoptosis. Both treatments resulted in suppression of activated (phosphorylated) forms of focal adhesion kinase (FAK) and Erk.

[17(20)E]- and [17(20)Z]-pregna-5,17(20)-dien-21-oylamides. Facile synthesis and primary evaluation for cancer cells proliferation.

Reaction of 17alpha-bromo-21-iodo-3beta-acetoxypregn-5-en-20-one with ammonia, primary, and secondary amines is simple and convenient method for preparation of [17(20)E]- and [17(20)Z]-pregna-5,17(20)-dien-21-oylamides. Synthesis and characteristics of 12 related amides are presented. Primary testing on cells proliferation indicated differing effects of synthesized compounds on androgen insensitive MCF-7 cells and androgen sensitive LNCaP cells.

Chlorin e6-cholesterol conjugate and its copper complex. Simple synthesis and entrapping in phospholipid vesicles.

Synthesis of 13'[(cholest-5-en)-3beta-yloxyethoxycarbamoyl]-chlorin e6 starting from methylpheophorbide and 3beta(2-hydroxy)-ethoxycholest-5-ene is presented, as well as the preparation of related copper complex. Both conjugates obtained may be simply incorporated in phosphatidyl choline vesicles.

Toxicity of (22R,23R)-22,23-dihydroxystigmastane derivatives to cultured cancer cells.

Toxicity of eight 22,23-dihydroxystigmastane derivatives (four pairs of (22R,23R)- and (22S,23S)-isomers differing in steroid backbone structure) to human breast carcinoma MCF-7 cells was compared. For every pair of structurally related compounds, (22R,23R) isomer was found to be significantly more toxic than (22S,23S) isomer. Computational analysis showed that side chain of (22R,23R)-22,23-dihydroxystigmastane derivatives is rigid, whereas that of (22S,23S)-isomers is rather flexible.

Integrin alpha5beta1 controls invasion of human breast carcinoma cells by direct and indirect modulation of MMP-2 collagenase activity.

Integrins control a variety of signal transduction pathways central to cell survival, proliferation, and differentiation and their functions and expression levels are altered in many types of cancer. Although alpha5beta1 is one of the most studied integrins in cancer, its functions in different aspects of this disease have not been completely elucidated. In particular, controversial data exist on its role in tumor invasion and metastasis.

Proteomic profiles of induced hepatotoxicity at the subcellular level.

In the present study proteomes of liver samples were analyzed after administration of phenobarbital (PB) or 3-methylcholantrene (3-MC) to mice. Liver cell homogenates were subfractionated by differential ultracentrifugation into cytosol and microsomes, which were subjected to 2-DE to generate the proteomic maps of these fractions. 2-DE yielded 1100 and 800 protein spots for microsomes and cytosol, respectively.

Atomic force microscopy revelation of molecular complexes in the multiprotein cytochrome P450 2B4-containing system.

The application of atomic force microscopy (AFM) to the identification and visualization of individual molecules and their complexes in a reconstituted monooxygenase P450 2B4 system without the phospholipid was demonstrated. The method employed in this study distinguishes the monomeric proteins from their binary complexes and, also, the binary from the ternary complexes. The AFM images of the full-length P450 2B4 system's constituent components - cytochrome P450 2B4 (2B4), NADPH-cytochrome P450 reductase and cytochrome b5 (b5), were obtained on highly-oriented pyrolitic graphite.