The Potential Role of Nitric Oxide in Halting Cancer Progression Through Chemoprevention

Nitric oxide (NO) in general plays a beneficial physiological role as a vasorelaxant and the role of NO is decided by its concentration present in physiological environments. NO either facilitates cancer-promoting characters or act as an anti-cancer agent. The dilemma in this regard still remains unanswered. This review summarizes the recent information on NO and its role in carcinogenesis and tumor progression, as well as dietary chemopreventive agents which have NO-modulating properties with safe cytotoxic profile. Understanding the molecular mechanisms and cross-talk modulating NO effect by these chemopreventive agents can allow us to develop better therapeutic strategies for cancer treatment

Analisis Karakteristik Saluran Komunikasi Satelit Bergerak Berdasarkan Rasio S/N Daerah Makassar Kondisi Clear Sky

Pada penelitian ini dilakukan pengukuran dan analisis signal strength GPS dengan menguji software berbasis PC dengan sistem operasi Linux. Menggunakan beberapa sofware untuk pengambilan data, pengolahan dan pengujian GPS receiver yang memiliki kemampuan menentukan posisi user pada kondisi mobile (bergerak) dengan tampilan visual pada MAP (peta). Penelitian dilakukan pada beberapa lokasi yang memiliki topografi yang diinginkan. Software-software berbasis PC yang digunakan pada Sitem Operasi Linux (Ubuntu v 10.10) yaitu GPSd (GPS Daemon), GPSpipe, XGPS, dan Tango GPS untuk Map (Peta) sedangkan untuk software berbasis PC pada Windows yaitu Matlab v 7.6. Software-software tersebut sudah mempunyai kemampuan menampilkan posisi satelit dan user beserta informasi yang sangat penting tanpa harus menerima data mentah lagi pada NMEA 0183 dalam kondisi mobile. Pengamatan dilakukan dengan mengumpulkan nilai S/N dari masing-masing satelit yang tertangkap oleh penerima di daerah kota Makassar.Penelitian ini terfokus pada tiga titik 3 (tiga) kondisi yakni LOS (line of sight), NLOS Moderate dan NLOS Heavy. Data yang diinput dari NMEA GPS pipe untuk 12 PRN disortir dan output yang dihasilkan dalam bentuk grafik kualitas signal strength setiap PRN satelit, untuk tampilan visual pada XGPS.Pada penelitian ini dilakukan pengukuran dan analisis signal strength GPS dengan menguji software berbasis PC dengan sistem operasi Linux. Menggunakan beberapa sofware untuk pengambilan data, pengolahan dan pengujian GPS receiver yang memiliki kemampuan menentukan posisi user pada kondisi mobile (bergerak) dengan tampilan visual pada MAP (peta). Penelitian dilakukan pada beberapa lokasi yang memiliki topografi yang diinginkan. Software-software berbasis PC yang digunakan pada Sitem Operasi Linux (Ubuntu v 10.10) yaitu GPSd (GPS Daemon), GPSpipe, XGPS, dan Tango GPS untuk Map (Peta) sedangkan untuk software berbasis PC pada Windows yaitu Matlab v 7.6. Software-software tersebut sudah mempunyai kemampuan menampilkan posisi satelit dan user beserta informasi yang sangat penting tanpa harus menerima data mentah lagi pada NMEA 0183 dalam kondisi mobile. Pengamatan dilakukan dengan mengumpulkan nilai S/N dari masing-masing satelit yang tertangkap oleh penerima di daerah kota Makassar.Penelitian ini terfokus pada tiga titik 3 (tiga) kondisi yakni LOS (line of sight), NLOS Moderate dan NLOS Heavy. Data yang diinput dari NMEA GPS pipe untuk 12 PRN disortir dan output yang dihasilkan dalam bentuk grafik kualitas signal strength setiap PRN satelit, untuk tampilan visual pada XGPS

(-)-Epigallocatechin-3-gallate reverses the expression of various tumor-suppressor genes by inhibiting DNA methyltransferases and histone deacetylases in human cervical cancer cells

There has been increasing evidence that numerous bioactive dietary agents can hamper the process of carcinogenesis by targeting epigenetic alterations including DNA methylation. This therapeutic approach is considered as a significant goal for cancer therapy due to the reversible nature of epigenetic-mediated gene silencing and warrants further attention. One such dietary agent, green tea catechin, (-)-epigallocatechin-3-gallate (EGCG) has been shown to modulate many cancer-related pathways. Thus, the present study was designed to investigate the role of EGCG as an epigenetic modifier in HeLa cells. DNA methyltransferase (DNMT) and histone deacetylase (HDAC) inhibition assays were conducted, and the transcription levels of DNMT3β and HDAC1 were assessed by enzymatic activity assay and RT-PCR, respectively. Furthermore, we studied the binding interaction of EGCG with DNMT3β and HDAC1 by molecular modeling as well as promoter DNA methylation and expression of retinoic acid receptor-â (RARâ), cadherin 1 (CDH1) and death-associated protein kinase-1 (DAPK1) in EGCG-treated HeLa cells by RT-PCR and MS-PCR. In the present study, time-dependent EGCG-treated HeLa cells were found to have a significant reduction in the enzymatic activity of DNMT and HDAC. However, the expression of DNMT3β was significantly decreased in a time-dependent manner whereas there was no significant change in HDAC1 expression. Molecular modeling data also supported the EGCG-mediated DNMT3β and HDAC1 activity inhibition. Furthermore, time-dependent exposure to EGCG resulted in reactivation of known tumor-suppressor genes (TSGs) in HeLa cells due to marked changes in the methylation of the promoter regions of these genes. Overall, the present study suggests that EGCG may have a significant impact on the development of novel epigenetic-based therapy

Sulforaphane inhibits growth of human breast cancer cells and augments the therapeutic index of the chemotherapeutic drug, gemcitabine

Phytochemicals are among the natural chemopreventive agents with most potential for delaying, blocking or reversing the initiation and promotional events of carcinogenesis. They therefore offer cancer treatment strategies to reduce cancer related death. One such promising chemopreventive agent which has attracted considerable attention is sulforaphane (SFN), which exhibits anti-cancer, anti-diabetic, and anti-microbial properties. The present study was undertaken to assess effect of SFN alone and in combination with a chemotherapeutic agent, gemcitabine, on the proliferative potential of MCF-7 cells by cell viability assay and authenticated the results by nuclear morphological examination. Further we analyzed the modulation of expression of Bcl-2 and COX-2 on treatment of these cells with SFN by RT-PCR. SFN showed cytotoxic effects on MCF-7 cells in a dose- and time-dependent manner via an apoptotic mode of cell death. In addition, a combinational treatment of SFN and gemcitabine on MCF-7 cells resulted in growth inhibition in a synergistic manner with a combination index (CI)\u3c1. Notably, SFN was found to significantly downregulate the expression of Bcl-2, an anti-apoptotic gene, and COX-2, a gene involved in inflammation, in a time-dependent manner. These results indicate that SFN induces apoptosis and anti-inflammatory effects on MCF-7 cells via downregulation of Bcl-2 and COX-2 respectively. The combination of SFN and gemcitabine may potentiate the efficacy of gemcitabine and minimize the toxicity to normal cells. Taken together, SFN may be a potent anti-cancer agent for breast cancer treatment

A trial sequential meta-analysis of TNF-α –308G\u3eA (rs800629) gene polymorphism and susceptibility to colorectal cancer

© 2019 The Author(s). Purpose: Tumor necrosis factor-α (TNF-α), secreted by the activated macrophages, may participate in the onset and progression of colorectal cancer (CRC). The association of TNF-α –308 G\u3eA (rs1800629) single-nucleotide polymorphism (SNP) with CRC risk has been investigated by many studies but the results are inconclusive. A trial sequential meta-analysis was performed for precise estimation of the relationship between TNF-α –308 G\u3eA gene polymorphism with CRC risk. Methods: Medline (PubMed), EMBASE (Excerpta-Medica) and Google Scholar were mined for relevant articles. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the significance of association. Results: The pooled analysis indicated no risk associated with TNF-α –308 G\u3eA SNP and overall CRC risk in five genetic comparison models, i.e. allelic (A vs. G: P = 0.524; OR = 1.074, 95% CI = 0.863–1.335), homozygous (AA vs. GG: P = 0.489; OR = 1.227, 95% CI = 0.688–2.188), heterozygous (AG vs. GG: P = 0.811; OR = 1.024, 95% CI = 0.843–1.244), dominant (AA+AG vs. GG: P = 0.630; OR = 1.055, 95% CI = 0.849–1.311) and recessive (AA vs. AG+GG: P = 0.549; OR = 1.181, 95% CI = 0.686–2.033). Subgroup analysis revealed that TNF-α –308 G\u3eA SNP is associated with reduced risk of CRC in Asian ethnicity. The study showed no publication bias. Conclusions: No association of TNF-α –308 G\u3eA SNP with overall CRC risk was found. This SNP is likely to be protective against CRC in Asian population when compared with Caucasian population. Larger prospective-epidemiological studies are warranted to elucidate the roles of TNF-α –308 G\u3eA SNP in the etiology of CRC and to endorse the present findings

Association of MBL2 gene polymorphisms with pulmonary tuberculosis susceptibility: Trial sequence meta-analysis as evidence

© 2019 Mandal et al. Background: Mannose-binding lectin (MBL) or mannose-binding protein (MBP), encoded by MBL2 gene and secreted by the liver, activates complement system through lectin pathway in innate immunity against the host’s infection. Conflictingly, a number of MBL2 variants, rs1800450 (A\u3eB), rs1800451 (A\u3eC), rs5030737 (A\u3eD), rs7096206 (Y\u3eX), rs11003125 (H\u3eL), and rs7095891 (P\u3eQ) allele, have been found to be associated with compromised serum levels and pulmonary tuberculosis (PTB) susceptibility. The present meta-analysis study was performed to evaluate the potential association of these MBL2 gene variants with PTB susceptibility. Materials and methods: A quantitative synthesis was performed on PubMed (Medline), EMBASE, and Google Scholar web database searches. A meta-analysis was performed to calculate the pooled odds ratios and 95% CIs for all the genetic models. Results: A total of 14 eligible studies were included to analyze their pooled data for associations between alleles, genotypes, and minor allele carriers. The statistical analysis revealed the significant reduced PTB risk with homozygous variant genotype of rs1800451 polymorphism (CC vs AA: P=0.043; OR =0.828, 95% CI =0.689–0.994). Contrary to this, the variant allele of rs5030737 polymorphism showed association with increased PTB risk (D vs A: P=0.026; OR =1.563, 95% CI =1.054–2.317). However, the other genetic models of rs1800450 (A\u3eB), rs7096206 (Y\u3eX), and rs11003125 (H\u3eL) MBL2 gene polymorphisms did not divulge any association with PTB susceptibility. Conclusion: The current meta-analysis concludes that rs1800451 (A\u3eC) and rs5030737 (A\u3eD) polymorphisms of MBL2 gene play a significant role in PTB susceptibility. Further, well-designed epidemiological studies with larger sample size including consideration of environmental factors are warranted for the future

Inhibitory effect of genistein on the invasive potential of human cervical cancer cells via modulation of matrix metalloproteinase-9 and tissue inhibitiors of matrix metalloproteinase-1 expression

Background: One of the most challenging stumbling blocks for the treatment of cancer is the ability of cancer cells to break the natural barriers and spread from its site of origin to non-adjacent regional and distant sites, accounting for high cancer mortality rates. Gamut experimental and epidemiological data advocate the use of pharmacological or nutritional interventions to inhibit or delay various stage(s) of cancer such as invasion and metastasis. Genistein, a promising chemopreventive agent, has gained considerable attention for its powerful anti-carcinogenic, anti-angiogenic and chemosensitizing activities. Methods: In this study, the cytotoxic potential of genistein on HeLa cells by cell viability assay and the mode of cell death induced by genistein were determined by nuclear morphological examination, DNA laddering assay and cell cycle analysis. Moreover, to establish its inhibitory effect on migration of HeLa cells, scratch wound assay was performed and these results were correlated with the expression of genes involved in invasion and migration (MMP-9 and TIMP-1) by RT-PCR. Results: The exposure of HeLa cells to genistein resulted in significant dose- and time-dependent growth inhibition, which was found to be mediated by apoptosis and cell cycle arrest at G2/M phase. In addition, it induced migration-inhibition in a time-dependent manner by modulating the expression of MMP-9 and TIMP-1. Conclusion: Our results signify that genistein may be an effective anti-neoplastic agent to prevent cancer cell growth and invasion and metastasis. Therefore therapeutic strategies utilizing genistein could be developed to substantially reduce cancer morbidity and mortality. © 2012 Elsevier Ltd

Sulforaphane Reverses the Expression of Various Tumor Suppressor Genes by Targeting DNMT3B and HDAC1 in Human Cervical Cancer Cells

Sulforaphane (SFN) may hinder carcinogenesis by altering epigenetic events in the cells; however, its molecular mechanisms are unclear. The present study investigates the role of SFN in modifying epigenetic events in human cervical cancer cells, HeLa. HeLa cells were treated with SFN (2.5 µM) for a period of 0, 24, 48, and 72 hours for all experiments. After treatment, expressions of DNMT3B, HDAC1, RARβ, CDH1, DAPK1, and GSTP1 were studied using RT-PCR while promoter DNA methylation of tumor suppressor genes (TSGs) was studied using MS-PCR. Inhibition assays of DNA methyl transferases (DNMTs) and histone deacetylases (HDACs) were performed at varying time points. Molecular modeling and docking studies were performed to explore the possible interaction of SFN with HDAC1 and DNMT3B. Time-dependent exposure to SFN decreases the expression of DNMT3B and HDAC1 and significantly reduces the enzymatic activity of DNMTs and HDACs. Molecular modeling data suggests that SFN may interact directly with DNMT3B and HDAC1 which may explain the inhibitory action of SFN. Interestingly, time-dependent reactivation of the studied TSGs via reversal of methylation in SFN treated cells correlates well with its impact on the epigenetic alterations accumulated during cancer development. Thus, SFN may have significant implications for epigenetic based therapy