Biomedical subjects

Alessandro Lentini

Publications and source records attributed to Alessandro Lentini.

4 recordsLinked to original sources

PubMed2006

Decrease of polyamine levels and enhancement of transglutaminase activity in selective reduction of B16-F10 melanoma cell proliferation induced by atrial natriuretic peptide.

The atrial natriuretic peptide (ANP) at physiological levels reduced the proliferation of highly metastatic murine (B16-F10) and human (SK-MEL 110) melanoma cell lines whereas rat aortic smooth muscle (RASM) cells were unaffected. In RASM cells, the levels of proliferation markers (putrescine, spermidine and spermine) increase after 24 h of epidermal growth factor (EGF) stimulation (RASM-EGF), but strongly decrease after 24 h of exposition to ANP. The B16-F10 cell line, which received no EGF stimulation, showed a similar decrease in polyamine content after ANP treatment. Furthermore, the enzymatic activity of a differentiation marker (transglutaminase) was increased for both RASM-EGF and B16-F10 cells after 24 h of treatment with 10(-10) mol/l ANP, concomitantly with the observed inhibition of polyamine biosynthesis and cell growth. Data obtained on B16-F10 cells treated with 8Br-GMPc or with an ANP analogue (cANF) support the involvement of the type C ANP receptor (NRP-C) in hormone effects. From the overall results, it appears that ANP may play a role in the inhibition of cellular growth under hyperproliferative conditions, as shown for RASM-EGF cells. The B16-F10 melanoma cell line showed similar results, but in the absence of mitogen stimulation. This observation suggests that the constitutive hyperproliferative state of tumor cells may be a sufficient condition to favor the ANP inhibitory effects on cell growth. This finding is particularly interesting in the light of a possible use of ANP as a potential selective antineoplastic agent.

Animals↗

PubMed2002

Platelet-derived growth factor inhibits basic fibroblast growth factor angiogenic properties in vitro and in vivo through its alpha receptor.

Basic fibroblast growth factor (bFGF) and platelet-derived growth factor-BB (PDGF-BB) modulate vascular wall cell function in vitro and angiogenesis in vivo. The aim of the current study was to determine how bovine aorta endothelial cells (BAECs) respond to the simultaneous exposure to PDGF-BB and bFGF. It was found that bFGF-dependent BAEC migration, proliferation, and differentiation into tubelike structures on reconstituted extracellular matrix (Matrigel) were inhibited by PDGF-BB. The role played by PDGF receptor alpha (PDGF-Ralpha) was investigated by selective stimulation with PDGF-AA, by blocking PDGF-BB-binding to PDGF-Ralpha with neomycin, or by transfecting cells with dominant-negative forms of the receptors to selectively impair either PDGF-Ralpha or PDGF-Rbeta function. In all cases, PDGF-Ralpha impairment abolished the inhibitory effect of PDGF-BB on bFGF-directed BAEC migration. In addition, PDGF-Ralpha phosphorylation was increased in the presence of bFGF and PDGF, as compared to PDGF alone, whereas mitogen-activated protein kinase phosphorylation was decreased in the presence of PDGF-BB and bFGF compared with bFGF alone. In vivo experiments showed that PDGF-BB and PDGF-AA inhibited bFGF-induced angiogenesis in vivo in the chick embryo chorioallantoic membrane assay and that PDGF-BB inhibited bFGF-induced angiogenesis in Matrigel plugs injected subcutaneously in CD1 mice. Taken together these results show that PDGF inhibits the angiogenic properties of bFGF in vitro and in vivo, likely through PDGF-Ralpha stimulation.

Animals↗

PubMed2002

Sugar-induced modification of fibroblast growth factor 2 reduces its angiogenic activity in vivo.

Both clinical and animal studies have shown that angiogenesis is impaired in diabetes mellitus; however, the mechanisms responsible for this effect are poorly characterized. The major aims of the present study were to evaluate the effect of hyperglycemia on fibroblast growth factor 2 (FGF2)-induced angiogenesis in vivo and to determine whether FGF2 non-enzymatic glycation occurs in hyperglycemic mice. New blood vessel formation was examined in reconstituted basement membrane protein (Matrigel) plugs containing FGF2 in control normoglycemic CD1 and in hyperglycemic nonobese diabetic (NOD) mice. FGF2-induced angiogenesis in NOD mice was inhibited by 75% versus control mice (P < 0.001). When recombinant FGF2 was mixed with Matrigel and injected in mice, it was found that recombinant FGF2 glycation was significantly enhanced in plugs from NOD versus control mice (P < 0.01). In the Boyden chamber assay, the chemotactic effect of glycated FGF2 toward endothelial cells was lower than that of unmodified FGF2 (P < 0.01). Further, FGF2 glycated in vitro and co-injected with Matrigel in CD1 mice was a weaker angiogenic stimulus than unglycated FGF2 (P < 0.005). These results indicate that FGF2-induced angiogenesis is inhibited in diabetic mice, FGF2 glycation is enhanced in hyperglycemic mice, and glycation markedly reduces FGF2 chemotactic effect in vitro and its angiogenic properties in vivo. Thus, FGF2 glycation may represent a mechanism responsible for the impairment of angiogenesis in diabetes mellitus.

Animals↗

PubMed2002

Theophylline-induced apoptosis is paralleled by protein kinase A-dependent tissue transglutaminase activation in cancer cells.

It has been reported that theophylline induces growth inhibition and apoptosis in tumour cells. We report that theophylline induces growth inhibition and apoptosis of several human epithelial tumour cells with an IC:50 of 2.5 mM after 48 h of exposure. Moreover, 2.5 mM theophylline induces the accumulation of cancer cells in S-phase of the cell cycle with a concomitant reduction in the percentage of tumour cells in G(1)/G(0) phase. These effects are paralleled by cytoskeletal remodelling with a consequent redistribution of actin fibers and shape change as demonstrated by fluorescence microscopy. The apoptotic death of tumour cells occurs together with an increase in the expression and activity of the pro-apoptotic enzyme tissue transglutaminase (tTGase). All these effects are promptly antagonized by the specific PKA inhibitor KT5720, suggesting the involvement of cAMP intracellular elevation and, consequently, PKA activation. On the other hand, growth inhibition and tTGase expression and activity are potentiated by retinoic acid, a tTGase inducer. Therefore, a mechanistic model of theophylline action and anti-tumour strategies based on the concomitant use of theophylline and agents that potentiate tTGase activity can be hypothesized.

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