Evaluation of polyamines as marker of melanoma cell proliferation and differentiation by an improved high-performance liquid chromatographic method.

The differentiation therapy is focused on the identification of new agents able to impair the proliferative and metastatic potential of cancer cells through the induction of differentiation. Although several markers of cell differentiation on tumor cells have been identified, their causal relationship with neoplastic competence has not been characterized in sufficient detail to propose their use as new pharmacological targets useful for the design of new differentiation agents. Polyamine level in cancer cells and in body fluids was proposed as potential marker of cell proliferation and differentiation.

Aloe-emodin exerts a potent anticancer and immunomodulatory activity on BRAF-mutated human melanoma cells.

Aim of this study was to extend the knowledge on the antineoplastic effect of aloe-emodin (AE), a natural hydroxyanthraquinone compound, both in metastatic human melanoma cell lines and in primary stem-like cells (melanospheres). Treatment with AE caused reduction of cell proliferation and induction of SK-MEL-28 and A375 cells differentiation, characterized by a marked increase of transamidating activity of transglutaminase whose expression remained unmodified. In vitro antimetastatic property of AE was evaluated by adhesion and Boyden chamber invasion assays.

Inhibition of cell proliferation, migration and invasion of B16-F10 melanoma cells by α-mangostin.

In this study, we have evaluated the potential antineoplastic effects of α-mangostin (α-M), the most representative xanthone in Garcinia mangostana pericarp, on melanoma cell lines. This xanthone markedly inhibits the proliferation of high-metastatic B16-F10 melanoma cells. Furthermore, by deeply analyzing which steps in the metastatic process are influenced by xanthone it was observed that α-M strongly interferes with homotypic aggregation, adhesion, plasticity and invasion ability of B16-F10 cells, probably by the observed reduction of metalloproteinase-9 activity.

Antineoplastic activity of strawberry (Fragaria×ananassa Duch.) crude extracts on B16-F10 melanoma cells.

The antiproliferative and differentiation potential of anthocyanin-rich strawberry fruit crude extracts (SE) were investigated on B16-F10 murine melanoma cells. Treatment of melanoma cells with SE produced a remarkable reduction of cell proliferation, paralleled with both the lowering of the intracellular levels of polyamine, and the enhancement of tissue transglutaminase (TG2, EC 2.3.

Tissue transglutaminase activity protects from cutaneous melanoma metastatic dissemination: an in vivo study.

The role of tissue transglutaminase (TG-2, TGase-2) in cancer development is still a fascinating field of research. The available reports do not elucidate fully its mechanism of action, due to the limitations of in vitro approaches. Therefore, to understand TG-2 role in cancer, we carried out an in vivo study with a more direct approach.

Hippocampal polyamine levels and transglutaminase activity are paralleling spatial memory retrieval in the C57BL/6J mouse.

Although a potential role for polyamines and transglutaminases (TGs) in memory mechanisms have been proposed, hippocampal spermine (SPM) and spermidine (SPD) levels as well as transamidating activity of TG in spatial memory have not been addressed yet. It was therefore the aim of the study to assess hippocampal polyamines and TG activity at the probe trial in a spatial memory paradigm. C57BL/6J mice (20 animals per group) were used for the experiments and divided into a trained and a yoked (untrained) group.

Transglutaminases: key regulators of cancer metastasis.

The ability to metastasize represents the most important characteristic of malignant tumors. The biological details of the metastatic process remain somewhat unknown, due to difficulties in studying tumor cell behaviour with high spatial and temporal resolution in vivo. Several lines of evidence involve transglutaminases (TGs) in the key stages of tumor progression cascade, even though the molecular mechanisms remain controversial.

Preclinical evaluation of the antineoplastic efficacy of 7-(2-hydroxyethyl)theophylline on melanoma cancer cells.

Differentiation-based therapeutics are an underutilized but potentially a significant option for cancer treatment. The effect of methylxanthines on melanoma cell differentiation has been well documented. We report the in-vitro and in-vivo anticancer potential of a theophylline analogue, 7-(2-hydroxyethyl)theophylline (HET), on murine B16-F10 and human Sk-Mel 110 metastatic melanoma cell lines.

Aloin enhances cisplatin antineoplastic activity in B16-F10 melanoma cells by transglutaminase-induced differentiation.

Aloin, a natural anthracycline from aloe plant, is a hydroxyanthraquinone derivative shown to have antitumor properties. This study demonstrated that aloin exerted inhibition of cell proliferation, adhesion and invasion abilities of B16-F10 melanoma cells under non-cytotoxic concentrations. Furthermore, aloin induced melanoma cell differentiation through the enhancement of melanogenesis and transglutaminase activity.

Aloe-emodin as antiproliferative and differentiating agent on human U937 monoblastic leukemia cells.

Aims: Aloe-emodin (AE), a plant derived anthraquinone, has been shown to have anticancer activity in various human cancer cell lines. We have recently reported that AE possesses a differentiative potential on melanoma cells. The purpose of this study was to investigate the possible modulation of defined markers of monocytic differentiation of AE on human U937 cell line.

Evidences for a role of protein cross-links in transglutaminase-related disease.

Transglutaminases (TGs) are a large family of related and ubiquitous enzymes that catalyze the cross-linking of a glutaminyl residue of a protein/peptide substrate to a lysyl residue of a protein/peptide co-substrate. Considerable and intense progress has been made in the understanding of the chemistry, molecular biology and cell biology of TGs. The knowledge that very different physiological and pathological processes are dependent on the presence of adequate levels of these cross-linking enzymes and on the amount of both free and protein-conjugated polyamines by TG, has generated an incredible amount of original research and review articles.

Spermidine delays eye lens opacification in vitro by suppressing transglutaminase-catalyzed crystallin cross-linking.

A Ca(2+)-dependent TG activity, identified in the eye lens of several mammalian species, has long been implicated in cataract formation. The precise mechanism of the involvement of this enzyme in this process remains unclear. The purpose of this work was to investigate the modulatory effect of polyamines on TG activity during rabbit eye lens in vitro opacification.

Polyamine concentration, transglutaminase activity and changes in protein synthesis during cryopreservation of shoot tips of apple variety Annurca.

Changes in metabolism and protein expression were analysed during cryopreservation of the ancient apple variety Annurca. Our experiments concerned transglutaminase activity, polyamine levels and protein expression associated with shoot tip dehydration. Cryopreserved shoot tips displayed 72% regrowth after treatment in liquid medium with 0.

Synergic effect of α-tocopherol and naringenin in transglutaminase-induced differentiation of human prostate cancer cells.

Prostate cancer is the second most common cancer in men worldwide. Its prevention and treatment remain a challenge to clinicians. Thus, there is an urgent need to discover novel, less toxic, and more effective therapies for patients.

Antitumor activity of theophylline in combination with Paclitaxel: a preclinical study on melanoma experimental lung metastasis.

Melanoma is one of the most aggressive forms of tumor, being responsible for about 80% of skin cancer deaths. Much effort is being directed at obtaining less-toxic anticancer therapies, and the combination between low cytotoxic doses of chemotherapeutic drugs and natural differentiative compounds seems to be of particular importance. The present study was undertaken to examine the possible role of a combination therapy using paclitaxel (PTX) as chemotherapeutic molecule and theophylline (TH) as differentiative agent in the prevention of metastasis in B16-F10 melanoma-bearing C57BL6/N mice.

Antitumor properties of aloe-emodin and induction of transglutaminase 2 activity in B16-F10 melanoma cells.

Aims: Aloe-emodin (AE), a natural hydroxyanthraquinone compound, has been reported as a potential anticancer agent. We studied the antineoplastic properties of AE on highly metastatic B16-F10 melanoma murine cells.

Main Methods: Cell proliferation was assessed by cell counting and viability was investigated using MTT and Trypan Bleu exclusion tests.

Similar antineoplastic effects of nimesulide, a selective COX-2 inhibitor, and prostaglandin E1 on B16-F10 murine melanoma cells.

There is now increasing evidence that a constitutive expression of cyclooxygenase 2 (COX-2) plays a role in the development and progression of malignant ectodermal tumours. In this study, we investigated whether the selective inhibition of COX-2 would be beneficial in melanoma treatment. Nimesulide, a selective inhibitor of COX-2 that causes the breakdown of proinflammatory 2-series prostaglandins (PG2), adversely affected the growth of B16-F10 melanoma cells through the induction of differentiation.

Anthraquinones danthron and quinizarin exert antiproliferative and antimetastatic activity on murine B16-F10 melanoma cells.

The anticancer potential of anthraquinones danthron and quinizarin on highly metastatic B16-F10 melanoma murine cells was investigated. Several parameters related to cell proliferation and differentiation, i.e.

Phytochemicals and protein-polyamine conjugates by transglutaminase as chemopreventive and chemotherapeutic tools in cancer.

Identifying novel chemopreventive and chemotherapeutic agents and targeting them to patients at high risk of developing cancer or following curative treatment may go some way towards improving prognosis. This review examines current knowledge regarding the chemopreventive and chemotherapeutic potential of phytochemicals in cancer. Both in vitro and animal studies demonstrate that several phytochemicals increase the activity of intracellular transglutaminases, a family of enzymes involved in cell differentiation, through the covalent conjugation of polyamine to cellular protein, with promising anti-neoplastic properties.

Post-translational modification of glutamine and lysine residues of HIV-1 aspartyl protease by transglutaminase increases its catalytic activity.

The human immunodeficiency virus type 1 aspartyl protease (HIV-1 PR) is a homodimeric aspartyl endopeptidase that is required for virus replication. HIV-1 PR was shown to act invitro as acyl-donor and -acceptor for both guinea pig liver transglutaminase (TG, EC 2.3.

Transglutaminase-dependent antiproliferative and differentiative properties of nimesulide on B16-F10 mouse melanoma cells.

The aim of this study was to collect evidences on the role of transglutaminase (TG, E.C.2.

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.

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.

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.

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.