Lycopene treatment of prostate cancer cell lines inhibits adhesion and migration properties of the cells

licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. Received: 2014.03.17; Accepted: 2014.05.23; Published: 2014.07.02 Background: Consumption of lycopene through tomato products has been suggested to reduce the risk of prostate cancer. Cellular adhesion and migration are important features of cancer progression and therefore a potential target for cancer interception. In the present study we have examined the in vitro effect of lycopene on these processes. Methods: Prostate cancer cell lines PC3, DU145 and immortalised normal prostate cell line PNT-2 were used. The adhesion assay consisted of seeding pre-treated cells onto Matrigel™, gently removing non-adherent cells and quantitating the adherent fraction using WST-1. Migratory potential was assessed using ibidi ™ migration chamber inserts, in which a cell-free zone between two confluent areas was allowed to populate over time and the migration measured. Results: 24 hour incubation of prostate cell lines with 1.15µmol/l lycopene showed a 40 % re-duction of cellular motility in case of PC3 cells, 58 % in DU145 cells and no effect was observed for PNT2 cells. A dose related inhibition of cell adhesion to a basement membrane in the form o

Honey and cancer:current status and future directions

Cancer is a leading cause of death worldwide and poses a challenge to treatment. With overwhelming evidence of the role played by diet and lifestyle in cancer risk and prevention, there is a growing interest into the search for chemopreventative or chemotherapeutic agents derived from natural products. Honey is an important source of bioactive compounds derived from plants and recent years have seen an increased interest in its anticancer properties. This review examines the role of honey in targeting key hallmarks of carcinogenesis, including uncontrolled proliferation, apoptosis evasion, angiogenesis, growth factor signalling, invasion, and inflammation. The evidence for honey as an adjunct to conventional cancer therapy is also presented. The review also highlights gaps in the current understanding and concludes that, before translation of evidence from cell culture and animal studies into the clinical setting, further studies are warranted to examine the effects of honey at a molecular level, as well as on cells in the tumour environment

Single nucleotide polymorphism in the genes of mce1 and mce4 operons of Mycobacterium tuberculosis: analysis of clinical isolates and standard reference strains

<p>Abstract</p> <p>Background</p> <p>The presence of four mammalian cell entry (<it>mce</it>) operons in <it>Mycobacterium tuberculosis </it>suggests the essentiality of the functions of the genes in these operons. The differential expression of the four <it>mce </it>operons in different phases of <it>in vitro </it>growth and in infected animals reported earlier from our laboratory further justifies the apparent redundancy for these genes in the genome.</p> <p>Here we investigate the extent of polymorphism in eight genes in the <it>mce1 </it>and <it>mce4 </it>operons of <it>M. tuberculosis </it>from four standard reference strains (H37Rv, H37Ra, LVS (Low Virulent Strain) and BCG) and 112 clinical isolates varying in their drug susceptibility profile, analysed by direct sequencing and Sequenom MassARRAY platform.</p> <p>Results</p> <p>We discovered 20 single nucleotide polymorphisms (SNPs) in the two operons. The comparative analysis of the genes of <it>mce1 </it>and <it>mce4 </it>operons revealed that <it>yrbE1A </it>[<it>Rv0167</it>] was most polymorphic in <it>mce1 </it>operon while <it>yrbE4A </it>[<it>Rv3501c</it>] and <it>lprN </it>[<it>Rv3495c</it>] had the highest number of SNPs in the <it>mce4 </it>operon. Of 20 SNPs, 12 were found to be nonsynonymous and were further analysed for their pathological relevance to <it>M. tuberculosis </it>using web servers PolyPhen and PMut, which predicted five deleterious nonsynonymous SNPs. A mutation from proline to serine at position 359 of the native Mce1A protein was most deleterious as predicted by both PolyPhen and PMut servers. Energy minimization of the structure of native Mce1A protein and mutated protein was performed using InsightII. The mutated Mce1A protein showed structural changes that could account for the effects of this mutation.</p> <p>Conclusions</p> <p>Our results show that SNPs in the coding sequences of <it>mce1 </it>and <it>mce4 </it>operons in clinical isolates can be significantly high. Moreover, <it>mce4 </it>operon is significantly more polymorphic than <it>mce1 </it>operon (p < 0.001). However, the frequency of nonsynonymous substitutions is higher in <it>mce1 </it>operon and synonymous substitutions are more in <it>mce4 </it>operon. <it>In silico </it>modeling predict that nonsynonymous SNP at <it>mce1A </it>[<it>Rv0169</it>], a virulence gene could play a pivotal role in causing functional changes in <it>M. tuberculosis </it>that may reflect upon the biology of the bacteria.</p

Design of a New Peptide Substrate Probe of the Putative Biomarker Legumain with Potential Application in Prostate Cancer Diagnosis ex vivo

The lysosomal endoprotease legumain (asparaginyl endoprotease) has been proposed as a putative biomarker in prostate tumours, in which the enzyme is markedly overexpressed. Overexpression, coupled with highly selective specificity for cleavage of substrates at the C-terminus of asparagine (Asn) residues, make legumain an attractive biochemical target for potential diagnosis, prognosis and treatment. We report the design, synthesis, characterisation and preliminary evaluation of a new rhodamine-B (Rho-B)-labelled legumain peptide substrate probe 5 [Rho-Pro-Ala-Asn-PEG-AQ(4-OH)] and its selective targeting to lysosomes in PC3 prostate cancer cells. Probe 5 was efficiently activated by recombinant human legumain to afford the high quantum yield reporter fluorophore tripeptide 4b (Rho-Pro-Ala-Asn-OH) with concomitant release of intense fluorescence. Furthermore, probe 5 was activated upon incubation with homogenates derived from fresh-frozen tissue material of prostatectomy specimens. Probe 5 represents a new viable biochemical tool for probing the activity of legumain with the potential to be used in ex vivo diagnostics in the cancer pathology laboratory

Comparison of LDL fatty acid and carotenoid concentrations and oxidative resistance of LDL in volunteers from countries with different rates of cardiovascular disease

Within Europe there are differences in cardiovascular disease (CVD) risk between countries and this might be related to dietary habits. Oxidative modification of LDL is suggested to increase the risk of CVD and both the fatty acid and antioxidant content of LDL can affect its oxidation. In the present study, concentration of LDL fatty acid and antioxidant micronutrients (tocopherols and carotenoids) and ex vivo oxidative resistance of LDL (lag phase) was compared in volunteers from five countries with different fruit and vegetable intakes and reported rates of CVD. Eighty volunteers (forty males, forty females per centre), age range 25-45 years, were recruited from France, Northern Ireland, UK, Republic of Ireland, The Netherlands, and Spain, and their LDL composition and lag phase were measured. There were some differences in LDL carotenoid and α-tocopherol concentrations between countries. α-Tocopherol was low and β- + γ-tocopherol were high (P<0·001) in the Dutch subjects. β-Carotene concentrations were significantly different between the French and Spanish volunteers, with French showing the highest and Spanish the lowest concentration. LDL lycopene was not different between centres in contrast to lutein, which was highest in French (twofold that in the Dutch and Spanish and threefold that in Northern Ireland and the Republic of Ireland, P<0·001). However absolute LDL saturated, monounsaturated, polyunsaturated and total unsaturated fatty acid concentrations were different between countries (P<0·001, total unsaturated highest in Northern Ireland) there was little difference in unsaturated:saturated fatty acid concentration ratios and no difference in polyunsaturated:saturated fatty acid concentration ratios. LDL from the Republic of Ireland (a region with a high rate of CVD) had greater resistance to Cu-stimulated oxidation than samples obtained from volunteers in other countries. In conclusion, LDL composition did not predict resistance to Cu-stimulated oxidation, nor is there evidence that LDL from volunteers in countries with lower rates of CVD have greater resistance to oxidatio