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  • Undergraduate Poster Abstracts
  • Pharmacology

    FRI-833 ANTICANCER EFFICACY OF PURIFIED COMPONENTS FROM PEARL GARLIC

    • Esmeralda Martinez ;
    • Tyra Hessel ;
    • Hamida Qavi ;

    FRI-833

    ANTICANCER EFFICACY OF PURIFIED COMPONENTS FROM PEARL GARLIC

    Esmeralda Martinez, Tyra Hessel, Hamida Qavi.

    University of Houston-Downtown, Houston, TX.

    For the past several years, mortality rates for breast cancer have decreased as awareness, diagnosis, and treatment have increased; however, it is still a debilitating disease that affects 1 in 8 women during their lifetime. The most common breast cancer treatments have severe side effects. Therefore, scientists and clinicians are always searching for new anticancer agents, especially from natural sources. Compounds derived from natural sources such as plants are promising for alternative treatments. Particularly, garlic has a history of medicinal properties which indicates a possibility of being a source of anticancer agents. The purpose of this study is to extract, purify, and identify compounds from a pearl garlic extract and test their anticancer efficacy in vitro. Previously, a methanol extract of pearl garlic showed 30% breast cancer cell growth inhibition. In this current study, components from pearl garlic have been purified using silica gel column chromatography, and 2 components with possible anticancer activity have been selected and are being characterized structurally. These components will be used for anticancer efficacy determination using breast cancer cells in vitro. When completed, this study will enhance our knowledge regarding the anticancer activity of components from pearl garlic and will offer the opportunity to design a rational approach to therapeutic invention of breast cancer.

    THU-827 CONSTRUCTING PGL3 DONOR PLASMID TO TEST HOMOLOGOUS RECOMBINATION IN RESPONSE TO DNA-PROTEIN CROSSLINKS

    • Elizabeth Lezama ;
    • Lisa Chesner ;
    • Colin Campbell ;

    THU-827

    CONSTRUCTING PGL3 DONOR PLASMID TO TEST HOMOLOGOUS RECOMBINATION IN RESPONSE TO DNA-PROTEIN CROSSLINKS

    Elizabeth Lezama1, Lisa Chesner2, Colin Campbell2.

    1Milwaukee School of Engineering, Milwaukee, WI, 2University of Minnesota, Minneapolis, MN.

    DNA-protein crosslinks (DPCs) form when proteins become covalently attached to chromosomal DNA. Known causative agents include numerous cancer chemotherapeutic drugs, ionizing radiation, and cigarette smoke. DPCs exhibit cytotoxic and mutagenic characteristics. They interrupt chromosomal replication and can cause mutations that can cause cancer. Currently, it is not known how cells recognize and respond to drug-induced DPCs. In order to gain insight into this question, a plasmid containing a 700 bp deletion in the luciferase gene was constructed. This 700 bp deletion causes the luciferase gene to be inactivated. A site-specific DPC, already constructed, will be co-transfected with the plasmid containing the inactivated luciferase gene into Chinese hamster cells, and a host cell reactivation assay will be performed to quantify DNA repair. We hypothesize that cells utilize homologous recombination to repair DPCs. To test this hypothesis, we will co-transfect an undamaged homologous recombination donor plasmid along with the DPC-containing plasmid. It is believed that homologous recombination with the donor plasmid enhances DPC repair and will yield more plasmids with an active luciferase gene. We anticipate that insight gained into the pathways that contribute to DPC repair will enhance efforts to understand how tumor cells develop resistance to certain anti-cancer therapeutics and may aid in the development of novel anti-cancer drugs.

    FRI-832 GENE EXPRESSION ANALYSIS TO UNDERSTAND THE ROLE OF ZINC STATUS ON ARSENIC-INDUCED OXIDATIVE STRESS RESPONSE

    • Sandra Alvarez ;
    • Vanessa De La Rosa ;
    • Laurie G. Hudson ;
    • Jim Liu ;

    FRI-832

    GENE EXPRESSION ANALYSIS TO UNDERSTAND THE ROLE OF ZINC STATUS ON ARSENIC-INDUCED OXIDATIVE STRESS RESPONSE

    Sandra Alvarez, Vanessa De La Rosa, Laurie G. Hudson, Jim Liu.

    The University of New Mexico College of Pharmacy, Albuquerque, NM.

    Groundwater contamination by inorganic arsenic is a global health concern. Within the Navajo tribal community, legacy uranium mining in the area has resulted in groundwater contamination by several toxic metals including arsenic. Long-term exposure to arsenic has been shown to cause an increased risk of cancer, developmental effects, cardiovascular disease, neurotoxicity, and diabetes. Previous studies have shown zinc deficiency and arsenic exposure alter the oxidative stress response, independently. The synergistic effect of zinc deficiency and arsenic exposure on oxidative stress remains unknown and has implications for exacerbating adverse health effects associated with arsenic exposure. The present study aims to investigate how zinc deficiency alters arsenic-induced oxidative stress. Changes in gene expression of key oxidative stress response genes will be measured using qPCR in arsenic treated control THP-1 cells and arsenic treated zinc deficient THP-1 cells. We expect to see increased expression of oxidative stress genes in arsenic-treated zinc deficient cells as compared to normal THP-1 cells, suggesting an increase in cellular oxidative stress as a result of zinc status. An understanding the role of zinc status lays the foundation for developing a zinc supplementation regimen for zinc-deficient populations at high risk for arsenic exposure.

    THU-832 THE ANTI-HYPERTENSIVE DRUG NITRENDIPINE IS TOXIC FOR MURINE NEUROBLASTOMA CELLS

    • Isabel Rivera ;
    • Antonio De Maio ;
    • David Cauvi ;
    • Nelson Arispe ;

    THU-832

    THE ANTI-HYPERTENSIVE DRUG NITRENDIPINE IS TOXIC FOR MURINE NEUROBLASTOMA CELLS

    Isabel Rivera1, Antonio De Maio1, David Cauvi1, Nelson Arispe2.

    1University of California, San Diego, La Jolla, CA, 2Uniformed Services University of the Health Sciences, Bethesda, MD.

    Alpha calcium-channel blockers are widely used for the treatment of hypertension. However, these antihypertension drugs may have secondary effects that have not been recognized yet. We investigated the effect of an alpha calcium channel blocker, nitrendipine (NTD), on the viability of neuronal cells. NTD binds to the voltage dependent L-type calcium channel, inhibiting its activity. L-type calcium channels consist of 4 subunits; α1, α2/δ, γ, and β; localized within the plasma membrane. NTD specifically binds with high affinity to the α1c subunit, which is critical for ion conductivity. We found that NTD inhibited the proliferation of murine neuroblastoma cells (N2A) as detected by the XTT method. In addition, NTD-induced cell death of N2A cells in a concentration-dependent manner as detected by flow cytometry using annexin 5 staining and propidium iodine permeability. To further investigate the toxic effect of NTD, the gene encoding for the α1c subunit (cacna1c) of the L-type calcium channels was knocked down by siRNA in N2A cells. We observed a decrease in cacna1c mRNA levels which did not alter the toxic effect of NTD. We concluded that the toxic effect of NTD on neuroblastoma cells is independent of binding to the L-type calcium channel. Further studies are required to investigate the mechanism of NTD-induced neuronal toxicity. However, it is important to note the potential toxic effect of this drug, which is widely prescribed for the treatment of hypertension.

    FRI-827 ACTIVATED PROTEIN C INDUCES THE ACTIVATION OF AKT AND PHOSPHORYLATION OF CAVEOLIN-1 IN ENDOTHELIAL CELLS

    • Mauricio Marquez Palencia ;
    • JoAnn Trejo ;

    FRI-827

    ACTIVATED PROTEIN C INDUCES THE ACTIVATION OF AKT AND PHOSPHORYLATION OF CAVEOLIN-1 IN ENDOTHELIAL CELLS

    Mauricio Marquez Palencia, JoAnn Trejo.

    University of California, San Diego, La Jolla, CA.

    Sepsis is a systemic inflammatory reaction caused by severe bacterial infection. In sepsis, an increase of cytokines and coagulation responses causes vascular leakage and tissue edema. Activated protein C (APC), an agonist for protease-activated receptor 1(PAR1), induces cytoprotective signaling in the endothelial cells that line blood vessels, protecting against vascular permeability. However, the FDA withdrew APC as a treatment for sepsis because of increased bleeding events. This project aims to determine the mechanism of APC cytoprotective signaling. Our hypothesis is that APC activation of PAR1 induces the phosphorylation of Akt and Caveolin-1 (Cav-1) in an Src-dependent manner in endothelial cells. Toward investigating the APC signaling pathway, we show through immunoblotting that Akt and Cav-1 are phosphorylated in endothelial cells stimulated with APC. We use pharmacological inhibitors and shRNA-mediated gene silencing to investigate the function of Src kinase and PAR1 in the APC-induced phosphorylation of Akt and Cav-1. In future studies, we will examine the role of Akt activation and Cav-1 phosphorylation in the protection of the endothelial barrier following APC stimulation. By understanding the APC cytoprotective signaling pathway, we may discover new therapeutic targets for sepsis treatment.

    THU-833 POLYPHARMACY IN PEDIATRIC TRANSPLANT PATIENTS RECEIVING TACROLIMUS

    • Jennifer Murillo ;
    • Jonathan Constance ;
    • Michael Spigarelli ;
    • Catherine M.T. Sherwin ;

    THU-833

    POLYPHARMACY IN PEDIATRIC TRANSPLANT PATIENTS RECEIVING TACROLIMUS

    Jennifer Murillo, Jonathan Constance, Michael Spigarelli, Catherine M.T. Sherwin.

    The University of Utah, Salt Lake City, UT.

    Polypharmacy describes the concurrent use of multiple drugs and is associated with an increased risk of adverse drug events. Pediatric transplant patients may have increased risk for potential drug-drug interactions. We studied and identified patterns of polypharmacy in pediatric patients who had received a heart, liver, kidney, or bone marrow transplant. This was a multicenter retrospective study of pediatric patients (28 days - 18 years) administered ≥ 2 doses of tacrolimus between 01/2006 and 12/2012. Transplant information was identified via hospital registry. Prism 6 (GraphPad) and R were used for statistical analyses. There were 376 hospitalizations for 184 (52% male) pediatric transplant patients within the first year of transplant, comprising bone marrow (BMT; n = 19), heart (n = 42), liver (n = 59), and kidney (n = 64) patients. Distinct drugs administered during the period of transplantation was highest for heart (median 44 [IQR 38-53]), liver (37 [33-54]), and BMT (45 [33-54]) as compared to kidney (19 [17-22]) recipients, p < 0.0001. Similarly, hospital lengths of stay (LOS) were less for kidney as compared to BMT, heart, or liver recipients in the transplant period. In contrast, the number of distinct drugs administered per hospital episode post-transplant was highest for BMT (19 [15-24]) compared to solid organs: heart (13 [10-17], p < 0.05), liver (13 [9-17], p < 0.001) and kidney (9 [7-12], p < 0.0001). No differences showed in LOS or in severity of illness/risk of mortality (SOI/ROM) scores among transplant types during post-transplant. Although similar in age, LOS, SOI, and ROM, BMT patients re-admitted to a hospital received twice as many distinct drugs per hospital episode than kidney transplant recipients.

    FRI-826 VARYING SENSITIVITY TO COCAINE SEEKING IN A RAT MODEL OF BINGE EATING BEHAVIOR

    • Allison Hester ;
    • Kimberlei Richardson ;

    FRI-826

    VARYING SENSITIVITY TO COCAINE SEEKING IN A RAT MODEL OF BINGE EATING BEHAVIOR

    Allison Hester, Kimberlei Richardson.

    Howard University, Washington, DC.

    Studies have shown that individuals diagnosed with a binge eating disorder also have a higher propensity for drug addiction. The cause for this co-occurrence is unknown, but similar neurochemical mechanisms may be involved in both disorders. We hypothesized that the acquisition, extinction, and reinstatement of cocaine self-administration would be distinct for 2 rat populations with differing eating phenotypes and that rats with binge-prone behavior would be more sensitive to drugs of abuse. Female Sprague Dawley rats underwent intermittent feeding tests to characterize their consumption of palatable pellets. Rats were assigned to either binge eating prone (BEP), binge eating resistant (BER), or binge eating neutral groups. BEP and BER rats were trained to self-administer cocaine using operant lever responding (fixed ratio-1 schedule, FR-1). Once operant responding was established, extinction training was done to diminish responding for cocaine. After extinction, both groups underwent cue-induced cocaine reinstatement. There was no significant difference in FR-1 training and extinction rats; however, there was a dose-dependent difference in lever pressing and cocaine infusions in BEP versus BER rats. BEP rats showed a significant increase in cocaine sensitivity at lower doses of cocaine versus BER rats (p < 0.05). Additionally, BEP rats showed a significant increase in cue-induced drug reinstatement versus BER rats (p < 0.05). The data demonstrate that BEP rats are more sensitive to cocaine and to environmental cues associated with cocaine. Future experiments will explore neurochemical systems that may cause the increased drug sensitivity exhibited by BEP rats.