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Articles 31 - 60 of 91

Full-Text Articles in Cell and Developmental Biology

Circular Rna Circhipk3 Promotes The Proliferation And Differentiation Of Chicken Myoblast Cells By Sponging Mir-30a-3p, Biao Chen, Jiao Yu, Lijin Guo, Mary Shannon Byers, Zhijun Wang, Xiaolan Chen, Haiping Xu, Qinghua Nie Feb 2019

Circular Rna Circhipk3 Promotes The Proliferation And Differentiation Of Chicken Myoblast Cells By Sponging Mir-30a-3p, Biao Chen, Jiao Yu, Lijin Guo, Mary Shannon Byers, Zhijun Wang, Xiaolan Chen, Haiping Xu, Qinghua Nie

Biology Student Research

Circular RNAs and microRNAs widely exist in various species and play crucial roles in multiple biological processes. It is essential to study their roles in myogenesis. In our previous sequencing data, both miR-30a-3p and circular HIPK3 (circHIPK3) RNA, which are produced by the third exon of the HIPK3 gene, were differentially expressed among chicken skeletal muscles at 11 embryo age (E11), 16 embryo age (E16), and 1-day post-hatch (P1). Here, we investigated their potential roles in myogenesis. Proliferation experiment showed that miR-30a-3p could inhibit the proliferation of myoblast. Through dual-luciferase assay and Myosin heavy chain (MYHC) immunofluorescence, we found that …

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Obesity-Induced Peritoneal Dissemination Of Ovarian Cancer And Dominant Recruitment Of Macrophages In Ascites, Rosa Mistica C. Ignacio, Eun-Sook Lee, Andrew J. Wilson, Alicia Beeghly-Fadiel, Margaret M. Whalen, Deok-Soo Son Dec 2018

Obesity-Induced Peritoneal Dissemination Of Ovarian Cancer And Dominant Recruitment Of Macrophages In Ascites, Rosa Mistica C. Ignacio, Eun-Sook Lee, Andrew J. Wilson, Alicia Beeghly-Fadiel, Margaret M. Whalen, Deok-Soo Son

Chemistry Faculty Research

One-fifth of cancer deaths are associated with obesity. Because the molecular mechanisms by which obesity affects the progression of ovarian cancer (OC) are poorly understood, we investigated if obesity could promote the progression of OC cells using the postmenopausal ob/ob mouse model and peritoneal dissemination of mouse ID8 OC cells. Compared to lean mice, obese mice had earlier OC occurrence, greater metastasis throughout the peritoneal cavity, a trend toward shorter survival, and higher circulating glucose and proinflammatory chemokine CXCL1 levels. Ascites in obese mice had higher levels of macrophages (Mφ) and chemokines including CCL2, CXCL12, CXCL13, G-CSF and M-CSF. Omental …

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Chemokine Network And Overall Survival In Tp53 Wild-Type And Mutant Ovarian Cancer, Rosa Mistica C. Ignacio, Eun-Sook Lee, Andrew J. Wilson, Alicia Beeghly-Fadiel, Margaret M. Whalen, Deok-Soo Son Aug 2018

Chemokine Network And Overall Survival In Tp53 Wild-Type And Mutant Ovarian Cancer, Rosa Mistica C. Ignacio, Eun-Sook Lee, Andrew J. Wilson, Alicia Beeghly-Fadiel, Margaret M. Whalen, Deok-Soo Son

Chemistry Faculty Research

Ovarian cancer (OC) has the highest mortality rate among gynecological malignancies. Because chemokine network is involved in OC progression, we evaluated associations between chemokine expression and survival in tumor suppressor protein p53 (TP53) wild-type (TP53WT) and mutant (TP53m) OC datasets. TP53 was highly mutated in OC compared to other cancer types. Among OC subtypes, CXCL14 was predominantly expressed in clear cell OC, and CCL15 and CCL20 in mucinous OC. TP53WT endometrioid OC highly expressed CXCL14 compared to TP53m, showing better progression-free survival but no difference in overall survival (OS). TP53m serous …

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Synthesis Of Interleukin 1 Beta And Interleukin 6 In Human Lymphocytes Is Stimulated By Tributyltin, Shyretha Brown, Mariam Boules, Nafisa Hamza, Xiaofei Wang, Margaret Whalen Jun 2018

Synthesis Of Interleukin 1 Beta And Interleukin 6 In Human Lymphocytes Is Stimulated By Tributyltin, Shyretha Brown, Mariam Boules, Nafisa Hamza, Xiaofei Wang, Margaret Whalen

Chemistry Faculty Research

Tributyltin (TBT) is a widespread environmental contaminant that is present in human blood and other tissues. It has been shown to disrupt the immune function of human natural killer (NK) cells and to alter the secretion of a number of pro-inflammatory cytokines from immune cells. Secretion of both interleukin 1β (IL-1β) and interleukin 6 (IL-6) from human lymphocytes can be increased dependent upon the level of TBT exposure. This study shows that the TBT-induced increases in secretion of both cytokines are due to TBT-induced increases in the synthesis of these proteins and not simply because of the release of pre-existing …

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Phytonutrient Genistein Is A Survival Factor For Pancreatic Β-Cells Via Gpr30-Mediated Mechanism, Jing Luo, Aihua Wang, Wei Zhen, Yao Wang, Hongwei Si, Zhenquan Jia, Hana Alkhalidy, Zhiyong Cheng, Elizabeth Gilbert, Bin Xu, Dongmin Liu Jun 2018

Phytonutrient Genistein Is A Survival Factor For Pancreatic Β-Cells Via Gpr30-Mediated Mechanism, Jing Luo, Aihua Wang, Wei Zhen, Yao Wang, Hongwei Si, Zhenquan Jia, Hana Alkhalidy, Zhiyong Cheng, Elizabeth Gilbert, Bin Xu, Dongmin Liu

Human Sciences Faculty Research

We previously discovered that phytonutrient genistein rapidly activates cAMP signaling in β-cells and improves islet mass in diabetic mice. However, the mechanism underlying these actions of genistein is still unclear. Here, we show that pharmacological or molecular inhibition of Gαs blocked genistein-stimulated adenylate cyclase activity in plasma membrane and intracellular cAMP production in INS1 cells and islets. Further, genistein stimulation of cAMP generation was abolished in islets exposed to a specific GPR30 inhibitor G15 or islets from GPR30 deficient (GPR30−/−) mice. In vivo, dietary provision of genistein (0.5 g/kg diet) significantly mitigated streptozotocin-induced hyperglycemia in male WT mice, which was …

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High Salt Induces P-Glycoprotein Mediated Treatment Resistance In Breast Cancer Cells Through Store Operated Calcium Influx, Duaa Babaer, Suneetha Amara, Michael Ivy, Yan Zhao, Philip E. Lammers, Jens M. Titze, Venkataswarup Tiriveedhi May 2018

High Salt Induces P-Glycoprotein Mediated Treatment Resistance In Breast Cancer Cells Through Store Operated Calcium Influx, Duaa Babaer, Suneetha Amara, Michael Ivy, Yan Zhao, Philip E. Lammers, Jens M. Titze, Venkataswarup Tiriveedhi

Biology Faculty Research

Recent evidence from our laboratory has demonstrated that high salt (Δ0.05 M NaCl) induced inflammatory response and cancer cell proliferation through salt inducible kinase-3 (SIK3) upregulation. As calcium influx is known to effect inflammatory response and drug resistance, we examined the impact of high salt on calcium influx in breast cancer cells. Treatment of MCF-7 and MDA-MB-231 cells with high salt induced an enhanced intracellular calcium intensity, which was significantly decreased by store operated calcium entry (SOCE) inhibitor co-treatment. Further, high salt induced P-glycoprotein (P-gp) mediated paclitaxel drug resistance in breast cancer cells. Murine tumor studies demonstrated that injection of …

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Vesicles Mimicking Normal And Cancer Cell Membranes Exhibit Differential Responses To The Cell-Penetrating Peptide Pep-1, Bashiyar Almarwani, Esther Nzuzi Phambu, Christopher Alexander, Ha Aimee T. Nguyen, Nsoki Phambu, Anderson Sunda-Meya Apr 2018

Vesicles Mimicking Normal And Cancer Cell Membranes Exhibit Differential Responses To The Cell-Penetrating Peptide Pep-1, Bashiyar Almarwani, Esther Nzuzi Phambu, Christopher Alexander, Ha Aimee T. Nguyen, Nsoki Phambu, Anderson Sunda-Meya

Chemistry Faculty Research

The cell-penetrating peptide (CPP) Pep-1 presents a great potential in drug delivery due to its intrinsic property to cross plasma membrane. However, its mechanism of entry into the cell remains unresolved. In this study, we compare the selectivity of Pep-1 towards vesicles mimicking normal and cancer cell membranes. The interaction was performed in a wide range of peptide-to-lipid molar ratios using infrared (IR), fluorescence, scanning electron microscopy (SEM), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) techniques. At low peptide concentration, fluorescence experiments show that lipid-phosphatidylserine (PS) seems to enable Pep-1 translocation into cancer cell membrane as evidenced by the …

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Tributyltin Stimulates Synthesis Of Interferon Gamma And Tumor Necrosis Factor Alpha In Human Lymphocytes, Shanieek Lawrence, Farah Ismail, Sarah Z. Jamal, Margaret M. Whalen Mar 2018

Tributyltin Stimulates Synthesis Of Interferon Gamma And Tumor Necrosis Factor Alpha In Human Lymphocytes, Shanieek Lawrence, Farah Ismail, Sarah Z. Jamal, Margaret M. Whalen

Chemistry Faculty Research

Tributyltin (TBT) is found in human blood and other tissues and thus is of considerable concern as to its effects on human health. Previous studies have demonstrated that TBT has detrimental effects on immune function. Recently, we found that exposures to TBT caused increased secretion of two important proinflammatory cytokines, tumor necrosis factor alpha (TNFα) and interferon gamma (IFNγ). Elevation of either of these cytokines has the potential to cause chronic inflammation, which is an important factor in a number of diseases including cancer. The current study examined the mechanism of TBT-induced elevations of TNFα and IFNγ secretion and found …

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Flame Retardants, Hexabromocyclododecane (Hcbd) And Tetrabromobisphenol A (Tbbpa), Alter Secretion Of Tumor Necrosis Factor Alpha (Tnfα) From Human Immune Cells, Sharia Yasmin, Margaret Whalen Jan 2018

Flame Retardants, Hexabromocyclododecane (Hcbd) And Tetrabromobisphenol A (Tbbpa), Alter Secretion Of Tumor Necrosis Factor Alpha (Tnfα) From Human Immune Cells, Sharia Yasmin, Margaret Whalen

Chemistry Faculty Research

Hexabromocyclododecane (HBCD) and tetrabromobisphenol A (TBBPA) are flame retardants, used in a variety of applications, which contaminate the environment and are found in human blood. HBCD and TBBPA have been shown to alter the tumor killing function of natural killer (NK) lymphocytes and the secretion of the inflammatory cytokines interferon gamma (IFNγ) and interleukin 1 beta (IL-1β). The current study examined the effects of HBCD and TBBPA on secretion of the critical pro-inflammatory cytokine tumor necrosis factor alpha (TNFα) from human immune cells. Preparations of human immune cells that ranged in complexity were studied to determine if the effects of …

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Cxcr2 Is A Negative Regulator Of P21 In P53-Dependent And Independent Manner Via Akt-Mediated Mdm2 In Ovarian Cancer, Rosa Mistica C. Ignacio, Yuan-Lin Dong, Syeda M. Kabir, Hyeongjwa Choi, Eun-Sook Lee, Alicia Beeghly-Fadiel, Margaret M. Whalen, Deok-Soo Son Jan 2018

Cxcr2 Is A Negative Regulator Of P21 In P53-Dependent And Independent Manner Via Akt-Mediated Mdm2 In Ovarian Cancer, Rosa Mistica C. Ignacio, Yuan-Lin Dong, Syeda M. Kabir, Hyeongjwa Choi, Eun-Sook Lee, Alicia Beeghly-Fadiel, Margaret M. Whalen, Deok-Soo Son

Chemistry Faculty Research

Ovarian cancer (OC) has the highest rate of mortality among gynecological malignancy. Chemokine receptor CXCR2 in OC is associated with poor outcomes. However, the mechanisms by which CXCR2 regulates OC proliferation remain poorly understood. We generated CXCR2-positive cells from parental p53 wild-type (WT), mutant and null OC cells, and assessed the roles of CXCR2 on proliferation of OC cells in p53-dependent and independent manner. CXCR2 promoted cell growth rate: p53WT > mutant = null cells. Nutlin-3, a p53 stabilizer, inhibited cell proliferation in p53WT cells, but had little effect in p53-mutant or null cells, indicating p53-dependence of CXCR2-mediated proliferation. CXCR2 decreased …

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Potential Anticancer Effect Of Prostratin Through Sik3 Inhibition, Dalal Alotaibi, Suneetha Amara, Terrance L. Johnson, Venkataswarup Tiriveedhi Dec 2017

Potential Anticancer Effect Of Prostratin Through Sik3 Inhibition, Dalal Alotaibi, Suneetha Amara, Terrance L. Johnson, Venkataswarup Tiriveedhi

Biology Faculty Research

Prostratin, a phorbol ester natural plant compound, has been demonstrated to exert an anti‑retroviral effect through activation of latent cluster of differentiation (CD)4+T lymphocytes and inhibition of viral entry into the cell through downregulation of chemokine receptor type 4 (CXCR4) expression. However, the potential effect of prostratin on cancer is yet to be defined. As CXCR4 is well known to induce cancer migration, it was hypothesized that prostratin induces an anti‑cancer effect through inhibition of CXCR4 expression. The authors previously demonstrated that high stimulating conditions (sub‑minimal IL‑17, 0.1 ng/ml, synergized with high salt, Δ0.05 M NaCl) promote breast cancer cell …

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Butyltin Compounds Alter Secretion Of Interleukin 6 From Human Immune Cells, Shyretha Brown, Wendy Wilburn, Tyesha Martin, Margaret Whalen Aug 2017

Butyltin Compounds Alter Secretion Of Interleukin 6 From Human Immune Cells, Shyretha Brown, Wendy Wilburn, Tyesha Martin, Margaret Whalen

Chemistry Faculty Research

Butyltins (BTs), tributyltin (TBT) and dibutyltin (DBT) are organotin compounds that have been used in a variety of industrial applications; as a result, these compounds have been found in human blood. Interleukin (IL)-6 is a proinflammatory mediator that is produced by T lymphocytes and monocytes. It is responsible for immune response regulation as well as tissue repair and cellular growth. Both BTs decrease the ability of human natural killer cells to destroy tumor cells and alter the secretion of proinflammatory cytokines tumor necrosis factor alpha, interferon gamma and IL-1 beta (β) from human lymphocytes ex vivo. Here, we show that …

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Critical Role Of Sik3 In Mediating High Salt And Il-17 Synergy Leading To Breast Cancer Cell Proliferation, Suneetha Amara, Ciera Majors, Bipradas Roy, Salisha Hill, Kristie L. Rose, Elbert L. Myles, Venkataswarup Tiriveedhi Jun 2017

Critical Role Of Sik3 In Mediating High Salt And Il-17 Synergy Leading To Breast Cancer Cell Proliferation, Suneetha Amara, Ciera Majors, Bipradas Roy, Salisha Hill, Kristie L. Rose, Elbert L. Myles, Venkataswarup Tiriveedhi

Biology Faculty Research

Chronic inflammation is a well-known precursor for cancer development and proliferation. We have recently demonstrated that high salt (NaCl) synergizes with sub-effective interleukin (IL)-17 to induce breast cancer cell proliferation. However, the exact molecular mechanisms mediating this effect are unclear. In our current study, we adopted a phosphoproteomic-based approach to identify salt modulated kinase-proteome specific molecular targets. The phosphoprotemics based binary comparison between heavy labelled MCF-7 cells treated with high salt (Δ0.05 M NaCl) and light labelled MCF-7 cells cultured under basal conditions demonstrated an enhanced phosphorylation of Serine-493 of SIK3 protein. The mRNA transcript and protein expression analysis of …

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Chain Length Effect On The Structure And Stability Of Antimicrobial Peptides Of The (Rw)N Series, Nsoki Phambu, Bashiyar Almarwani, Arlette M. Garcia, Nafisa S. Hamza, Amira Muhsen, Jacqueline E. Baidoo, Anderson Sunda-Meya May 2017

Chain Length Effect On The Structure And Stability Of Antimicrobial Peptides Of The (Rw)N Series, Nsoki Phambu, Bashiyar Almarwani, Arlette M. Garcia, Nafisa S. Hamza, Amira Muhsen, Jacqueline E. Baidoo, Anderson Sunda-Meya

Chemistry Faculty Research

Three peptides containing (RW)n-NH2 units (where n=4, 6, and 8) have been chosen to study the effect of the chain length on the structure and stability of the peptide using Fourier transform infrared (FTIR), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC) techniques. Their interactions with Escherichia coli (E. coli) membrane mimetic vesicles are discussed. Infrared results indicate that addition of (RW)n-NH2 units increases intermolecular H bonds with antiparallel orientation. TGA and DSC results reveal that (RW)6-NH2 shows the optimal chain length in terms of stability and all three peptides show a preferential interaction with one …

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Avian And Mammalian Facilitative Glucose Transporters, Mary Shannon Byers, Christianna Howard, Xiaofei Wang Apr 2017

Avian And Mammalian Facilitative Glucose Transporters, Mary Shannon Byers, Christianna Howard, Xiaofei Wang

Biology Faculty Research

The GLUT members belong to a family of glucose transporter proteins that facilitate glucose transport across the cell membrane. The mammalian GLUT family consists of thirteen members (GLUTs 1–12 and H+-myo-inositol transporter (HMIT)). Humans have a recently duplicated GLUT member, GLUT14. Avians express the majority of GLUT members. The arrangement of multiple GLUTs across all somatic tissues signifies the important role of glucose across all organisms. Defects in glucose transport have been linked to metabolic disorders, insulin resistance and diabetes. Despite the essential importance of these transporters, our knowledge regarding GLUT members in avians is fragmented. It is clear that …

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Inflammatory Role Of High Salt Level In Tumor Microenvironment (Review), Suneetha Amara, Venkataswarup Tiriveedhi Mar 2017

Inflammatory Role Of High Salt Level In Tumor Microenvironment (Review), Suneetha Amara, Venkataswarup Tiriveedhi

Biology Faculty Research

Chronic inflammation is known to play a critical role in cancer development and progression. High salt is known to mediate several chronic inflammatory diseases including hypertension, myocardial infarction, neurological ischemic attack, autoimmune diseases and cancers. High salt level is shown to induce angiogenesis and immune-dysfunction, both of which play a direct role in cancer proliferation. Furthermore, salt has been suggested to enhance Warburg-like metabolic phenotype in cancer cells and at the same time also induce pro-tumor MΦ2-macrophage phenotype. Recent studies have identified several molecular targets such as tonicity specific transcript factor NFAT5/TonEBP, sodium ion channel γENaC, and vascular endothelial growth …

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The Five Immune Forces Impacting Dna-Based Cancer Immunotherapeutic Strategy, Suneetha Amara, Venkataswarup Tiriveedhi Mar 2017

The Five Immune Forces Impacting Dna-Based Cancer Immunotherapeutic Strategy, Suneetha Amara, Venkataswarup Tiriveedhi

Biology Faculty Research

DNA-based vaccine strategy is increasingly realized as a viable cancer treatment approach. Strategies to enhance immunogenicity utilizing tumor associated antigens have been investigated in several pre-clinical and clinical studies. The promising outcomes of these studies have suggested that DNA-based vaccines induce potent T-cell effector responses and at the same time cause only minimal side-effects to cancer patients. However, the immune evasive tumor microenvironment is still an important hindrance to a long-term vaccine success. Several options are currently under various stages of study to overcome immune inhibitory effect in tumor microenvironment. Some of these approaches include, but are not limited to, …

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Effects Of Al3+ And La3+ Trivalent Metal Ions On Tomato Fruit Proteomes, Sasikiran Sangireddy, Ikenna Okekeogbu, Zhujia Ye, Suping Zhou, Kevin J. Howe, Tara Fish, Theodore W. Thannhauser Feb 2017

Effects Of Al3+ And La3+ Trivalent Metal Ions On Tomato Fruit Proteomes, Sasikiran Sangireddy, Ikenna Okekeogbu, Zhujia Ye, Suping Zhou, Kevin J. Howe, Tara Fish, Theodore W. Thannhauser

Agricultural and Environmental Sciences Faculty Research

The tomato (Solanum lycopersicum) ripening process from mature green (MG) to turning and then to red stages is accompanied by the occurrences of physiological and biochemical reactions, which ultimately result in the formation of the flavor, color and texture of ripe fruits. The two trivalent metal ions Al3+ and La3+ are known to induce different levels of phytotoxicity in suppressing root growth. This paper aims to understand the impacts of these two metal ions on tomato fruit proteomes. Tomato ‘Micro-Tom’ plants were grown in a hydroponic culture system supplemented with 50 μM aluminum sulfate (Al2 (SO4)3 …

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Effects Of Pentachlorophenol And Dichlorodiphenyltrichloroethane On Secretion Of Interferon Gamma (Ifnγ) And Tumor Necrosis Factor Alpha (Tnfα) From Human Immune Cells, Reda Massawe, Leon Drabo, Margaret Whalen Jan 2017

Effects Of Pentachlorophenol And Dichlorodiphenyltrichloroethane On Secretion Of Interferon Gamma (Ifnγ) And Tumor Necrosis Factor Alpha (Tnfα) From Human Immune Cells, Reda Massawe, Leon Drabo, Margaret Whalen

Chemistry Faculty Research

Pentachlorophenol (PCP) and dichlorodiphenyltrichloroethane (DDT) are pesticides that have been widely used and significantly contaminate the environment. Both are found in human blood and have been shown to alter the lytic and binding function of human natural killer (NK) cells. Interferon gamma (IFNγ) and tumor necrosis factor alpha (TNFα) are pro-inflammatory cytokines, which regulate immune responsiveness to pathogens and tumors. Their levels require very tight control to prevent loss of immune competence or excessive inflammation. Here, we examined the capacity of PCP and DDT to alter the secretion of these critical pro-inflammatory cytokines from increasingly reconstituted (more complex) preparations of …

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Microtubule Actin Cross-Linking Factor 1, A Novel Target In Glioblastoma, Najlaa Afghani, Toral Mehta, Jialiang Wang, Nan Tang, Omar Skalli, Quincy A. Quick Dec 2016

Microtubule Actin Cross-Linking Factor 1, A Novel Target In Glioblastoma, Najlaa Afghani, Toral Mehta, Jialiang Wang, Nan Tang, Omar Skalli, Quincy A. Quick

Biology Faculty Research

Genetic heterogeneity is recognized as a major contributing factor of glioblastoma resistance to clinical treatment modalities and consequently low overall survival rates. This genetic diversity results in variations in protein expression, both intratumorally and between individual glioblastoma patients. In this regard, the spectraplakin protein, microtubule actin cross-linking factor 1 (MACF1), was examined in glioblastoma. An expression analysis of MACF1 in various types of brain tumor tissue revealed that MACF1 was predominately present in grade III-IV astroctyomas and grade IV glioblastoma, but not in normal brain tissue, normal human astrocytes and lower grade brain tumors. Subsequent genetic inhibition experiments showed that …

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Proprotein Convertase Processing Enhances Peroxidasin Activity To Reinforce Collagen Iv, Selene Colon, Gautam Bhave Oct 2016

Proprotein Convertase Processing Enhances Peroxidasin Activity To Reinforce Collagen Iv, Selene Colon, Gautam Bhave

Biology Student Research

The basement membrane (BM) is a form of extracellular matrix that underlies cell layers in nearly all animal tissues. Type IV collagen, a major constituent of BMs, is critical for tissue development and architecture. The enzyme peroxidasin (Pxdn), an extracellular matrix-associated protein, catalyzes the formation of structurally reinforcing sulfilimine cross-links within the collagen IV network, an event essential to basement membrane integrity. Although the catalytic function of Pxdn is known, the regulation of its activity remains unclear. In this work we show through N-terminal sequencing, pharmacologic studies, and mutational analysis that proprotein convertases (PCs) proteolytically process human Pxdn at Arg-1336, …

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Exposures To The Environmental Toxicants Pentachlorophenol (Pcp) And Dichlorodiphenyltrichloroethane (Ddt) Modify Secretion Of Interleukin 1-Beta (Il-1Β) From Human Immune Cells, Tamara J. Martin, Margaret M. Whalen Sep 2016

Exposures To The Environmental Toxicants Pentachlorophenol (Pcp) And Dichlorodiphenyltrichloroethane (Ddt) Modify Secretion Of Interleukin 1-Beta (Il-1Β) From Human Immune Cells, Tamara J. Martin, Margaret M. Whalen

Chemistry Faculty Research

Pentachlorophenol (PCP) and Dichlorodiphenyltrichloroethane (DDT) are environmental contaminants found in human blood. Previous studies have shown that PCP and DDT inhibit the lytic function of highly purified human natural killer (NK) lymphocytes and decrease the expression of several surface proteins on NK cells. Interleukin-1 βeta (IL-1β) is a cytokine produced by lymphocytes and monocytes, and anything that elevates its levels inappropriately can lead to chronic inflammation, which among other consequences can increase tumor development and invasiveness. Here, PCP and DDT were examined for their ability to alter secretion of IL-1β from immune cell preparations of various complexity: NK cells; monocyte-depleted …

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Nfat5/Stat3 Interaction Mediates Synergism Of High Salt With Il-17 Towards Induction Of Vegf-A Expression In Breast Cancer Cells, Suneetha Amara, Dalal Alotaibi, Venkataswarup Tiriveedhi Jun 2016

Nfat5/Stat3 Interaction Mediates Synergism Of High Salt With Il-17 Towards Induction Of Vegf-A Expression In Breast Cancer Cells, Suneetha Amara, Dalal Alotaibi, Venkataswarup Tiriveedhi

Biology Faculty Research

Chronic inflammation has been considered an important player in cancer proliferation and progression. High salt (sodium chloride) levels have been considered a potent inducer of chronic inflammation. In the present study, the synergistic role of high salt with interleukin (IL)‑17 towards induction of the inflammatory and angiogenic stress factor vascular endothelial growth factor (VEGF)‑A was investigated. Stimulation of MCF-7 breast cancer cells with high salt (0.2 M NaCl) and sub‑minimal IL‑17 (1 ng/ml) enhanced the expression of VEGF-A (2.9 and 2.6-fold, respectively, P<0.05) compared with untreated cells. Furthermore, co‑treatment with both high salt and sub‑minimal IL‑17 led to a 5.9‑fold increase in VEGF‑A expression (P<0.01), thus suggesting a synergistic role of these factors. VEGF‑A promoter analysis and specific small interfering RNA knock‑down of transcription factors revealed that high salt induced VEGF‑A expression through nuclear factor of activated T‑cells (NFAT)5, while IL‑17 induced VEGF‑A expression via signal transducer and activator of transcription (STAT)3 signaling mechanisms. Treatment of normal human aortic endothelial cells with the supernatant of activated MCF‑7 cells enhanced cell migration and induced expression of migration‑specific factors, including vascular cell adhesion protein, β1 integrin and cluster of differentiation 31. These data suggest that high salt levels synergize with pro‑inflammatory IL‑17 to potentially induce cancer progression and metastasis through VEGF‑A expression. Therefore, low‑salt diet, anti‑NFAT5 and anti‑STAT3 therapies may provide novel avenues for enhanced efficiency of the current cancer therapy.

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Oleanolic Acid Inhibits High Salt-Induced Exaggeration Of Warburg-Like Metabolism In Breast Cancer Cells, Suneetha Amara, Mu Zheng, Venkataswarup Tiriveedhi May 2016

Oleanolic Acid Inhibits High Salt-Induced Exaggeration Of Warburg-Like Metabolism In Breast Cancer Cells, Suneetha Amara, Mu Zheng, Venkataswarup Tiriveedhi

Biology Faculty Research

Cancer cells have a proliferative advantage by utilizing intermediates of aerobic glycolysis (Warburg effect) for their macromolecule synthesis. Although the exact causes of this Warburg effect are unclear, high osmotic stress in solid tumor microenvironment is considered one of the important factors. Oleanolic acid (OA) is known to exert anti-inflammatory and anti-cancer effect. In our current studies, using breast cancer cell lines, we determined the protective role of OA in high salt-mediated osmotic stress-induced cancer growth. Hypertonic (0.16 M NaCl) culture conditions enhanced the cancer cell growth (26 %, p < 0.05) and aerobic glycolysis as marked by increased glucose consumption (34 %, p < 0.05) and lactate production (25 %, p < 0.05) over untreated cells. This effect was associated with increased expression and activity of key rate-limiting enzymes of aerobic glycolysis, namely hexokinase, pyruvate kinase type M2, and lactate dehydrogenase A. Interestingly, this high salt-mediated enhanced expression of aerobic glycolytic enzymes was efficiently reversed by OA along with the decreased cancer cell proliferation. In cancer cells, enhanced aerobic glycolysis is associated with the decreased mitochondrial activity and mitochondrial-associated caspase activity. As expected, high salt further inhibited the mitochondrial related cytochrome oxidase and caspase-3 activity. However, OA efficiently reversed the high salt-mediated inhibition of cytochrome oxidase, caspase activity, and pro-apoptotic Bax expression, thus suggesting that OA induced mitochondrial activity and enhanced apoptosis. Taken together, our data indicate that OA efficiently reverses the enhanced Warburg-like metabolism induced by high salt-mediated osmotic stress along with potential application of OA in anti-cancer therapy.

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Oleanolic Acid Inhibits High Salt-Induced Exaggeration Of Warburg-Like Metabolism In Breast Cancer Cells, Suneetha Amara, Mu Zheng, Venkataswarup Tiriveedhi May 2016

Oleanolic Acid Inhibits High Salt-Induced Exaggeration Of Warburg-Like Metabolism In Breast Cancer Cells, Suneetha Amara, Mu Zheng, Venkataswarup Tiriveedhi

Chemistry Faculty Research

Cancer cells have a proliferative advantage by utilizing intermediates of aerobic glycolysis (Warburg effect) for their macromolecule synthesis. Although the exact causes of this Warburg effect are unclear, high osmotic stress in solid tumor microenvironment is considered one of the important factors. Oleanolic acid (OA) is known to exert anti-inflammatory and anti-cancer effect. In our current studies, using breast cancer cell lines, we determined the protective role of OA in high salt-mediated osmotic stress-induced cancer growth. Hypertonic (0.16 M NaCl) culture conditions enhanced the cancer cell growth (26 %, p < 0.05) and aerobic glycolysis as marked by increased glucose consumption (34 %, p < 0.05) and lactate production (25 %, p < 0.05) over untreated cells. This effect was associated with increased expression and activity of key rate-limiting enzymes of aerobic glycolysis, namely hexokinase, pyruvate kinase type M2, and lactate dehydrogenase A. Interestingly, this high salt-mediated enhanced expression of aerobic glycolytic enzymes was efficiently reversed by OA along with the decreased cancer cell proliferation. In cancer cells, enhanced aerobic glycolysis is associated with the decreased mitochondrial activity and mitochondrial-associated caspase activity. As expected, high salt further inhibited the mitochondrial related cytochrome oxidase and caspase-3 activity. However, OA efficiently reversed the high salt-mediated inhibition of cytochrome oxidase, caspase activity, and pro-apoptotic Bax expression, thus suggesting that OA induced mitochondrial activity and enhanced apoptosis. Taken together, our data indicate that OA efficiently reverses the enhanced Warburg-like metabolism induced by high salt-mediated osmotic stress along with potential application of OA in anti-cancer therapy.

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Dibutyltin-Induced Alterations Of Interleukin 1beta Secretion From Human Immune Cells, Shyretha Brown, Shahin Tehrani, Margaret M. Whalen May 2016

Dibutyltin-Induced Alterations Of Interleukin 1beta Secretion From Human Immune Cells, Shyretha Brown, Shahin Tehrani, Margaret M. Whalen

Chemistry Faculty Research

Dibutyltin (DBT) is used to stabilize polyvinyl chloride plastics (including pipes that distribute drinking water) and as a de-worming agent in poultry. DBT is found in human blood, and DBT exposures alter the secretion of tumor necrosis factor alpha and interferon gamma from lymphocytes. Interleukin (IL)-1β is a proinflammatory cytokine that regulates cellular growth, tissue restoration and immune response regulation. IL-1β plays a role in increasing invasiveness of certain tumors. This study reveals that exposures to DBT (24 h, 48 h and 6 days) modify the secretion of IL-1β from increasingly reconstituted preparations of human immune cells (highly enriched human …

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Sodium Channel Γenac Mediates Il-17 Synergized High Salt Induced Inflammatory Stress In Breast Cancer Cells, Suneetha Amara, Michael T. Ivy, Elbert L. Myles, Venkataswarup Tiriveedhi Mar 2016

Sodium Channel Γenac Mediates Il-17 Synergized High Salt Induced Inflammatory Stress In Breast Cancer Cells, Suneetha Amara, Michael T. Ivy, Elbert L. Myles, Venkataswarup Tiriveedhi

Biology Faculty Research

Chronic inflammation is known to play a critical role in the development of cancer. Recent evidence suggests that high salt in the tissue microenvironment induces chronic inflammatory milieu. In this report, using three breast cancer-related cell lines, we determined the molecular basis of the potential synergistic inflammatory effect of sodium chloride (NaCl) with interleukin-17 (IL-17). Combined treatment of high NaCl (0.15M) with sub-effective IL-17 (0.1nM) induced enhanced growth in breast cancer cells along with activation of reactive nitrogen and oxygen (RNS/ROS) species known to promote cancer. Similar effect was not observed with equi-molar mannitol. This enhanced of ROS/RNS activity correlates …

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Effect Of Quercetin, Genistein And Kaempferol On Glutathione And Glutathione-Redox Cycle Enzymes In 3t3-L1 Preadipocytes, William Y. Boadi, Paul K. Amartey, Andrew Lo Sep 2015

Effect Of Quercetin, Genistein And Kaempferol On Glutathione And Glutathione-Redox Cycle Enzymes In 3t3-L1 Preadipocytes, William Y. Boadi, Paul K. Amartey, Andrew Lo

Chemistry Faculty Research

Context and objective: Many studies have shown that cellular redox potential is largely determined by glutathione (GSH), which accounts for more than 90% of cellular nonprotein thiols. The aim of this study was to delineate the effect of three flavonoids – namely, quercetin, kaempferol and genistein – and exogenous GSH on oxidative damage by the Fenton’s pathway through the GSH and GSH-redox cycle enzymes in 3T3-L1 cells. Materials and methods: 3T3-L1 preadipocytes were exposed to each flavonoid and GSH at concentrations of 0, 5, 10, 15, 20 and 25 µM and then GSH levels and activities of glutathione peroxidase (GSH-Px), …

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Hexabromocyclododecane And Tetrabromobisphenol A Alter Secretion Of Interferon Gamma (Ifn-Γ) From Human Immune Cells, Haifa Almughamsi, Margaret M. Whalen Aug 2015

Hexabromocyclododecane And Tetrabromobisphenol A Alter Secretion Of Interferon Gamma (Ifn-Γ) From Human Immune Cells, Haifa Almughamsi, Margaret M. Whalen

Chemistry Faculty Research

Hexabromocyclododecane (HBCD) and tetrabromobisphenol A (TBBPA) are brominated flame-retardant compounds used in a variety of applications including insulation, upholstery, and epoxy resin circuit boards. Interferon gamma (IFN-γ) is an inflammatory cytokine produced by activated T and NK cells that regulates immune responsiveness. HBCD and TBBPA are found in human blood, and previous studies have shown that they alter the ability of human natural killer (NK) lymphocytes to destroy tumor cells. This study examines whether HBCD and TBBPA affect the secretion of IFN-γ from increasingly complex preparations of human immune cells—purified NK cells, monocyte-depleted (MD) peripheral blood mononuclear cells (PBMCs), and …

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Activation Of Protein Kinase C And Protein Kinase D In Human Natural Killer Cells: Effects Of Tributyltin, Dibutyltin, And Tetrabromobisphenol A, Krupa Rana, Margaret Whalen Jul 2015

Activation Of Protein Kinase C And Protein Kinase D In Human Natural Killer Cells: Effects Of Tributyltin, Dibutyltin, And Tetrabromobisphenol A, Krupa Rana, Margaret Whalen

Chemistry Faculty Research

Up to now, the ability of target cells to activate protein kinase C (PKC) and protein kinase D (PKD) (which is often a downstream target of PKC) has not been examined in natural killer (NK) lymphocytes. Here we examined whether exposure of human NK cells to lysis sensitive tumor cells activated PKC and PKD. The results of these studies show for the first time that activation of PKC and PKD occurs in response to target cell binding to NK cells. Exposure of NK cells to K562 tumor cells for 10 and 30 min increased phosphorylation/activation of both PKC and PKD …

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