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Anticancer Activity Of A Thymidine Quinoxaline Conjugate Is Modulated By Cytosolic Thymidine Pathways, Qiong Wei, Haijuan Liu, Honghao Zhou, Dejun Zhang, Zhiwei Zhang, Qibing Zhou

Medicinal Chemistry Publications

Background

High levels of thymidine kinase 1 (TK1) and thymidine phosphorylase (TYMP) are key molecular targets by thymidine therapeutics in cancer treatment. The dual roles of TYMP as a tumor growth factor and a key activation enzyme of anticancer metabolites resulted in a mixed outcome in cancer patients. In this study, we investigated the roles of TK1 and TYMP on a thymidine quinoxaline conjugate to evaluate an alternative to circumvent the contradictive role of TYMP.

Methods

TK1 and TYMP levels in multiple liver cell lines were assessed along with the cytotoxicity of the thymidine conjugate. Cellular accumulation of the thymidine …

6-Hydroxyflavone And Derivatives Exhibit Potent Anti-Inflammatory Activity Among Mono-, Di- And Polyhydroxylated Flavones In Kidney Mesangial Cells, Xing Wang, Zhiwei Wang, Preetpal Singh Sidhu, Umesh R. Desai, Qibing Zhou

Medicinal Chemistry Publications

Inflammatory responses by kidney mesangial cells play a critical role in the glomerulonephritis. The anti-inflammatory potential of nineteen mono-, di- and polyhydroxylated flavones including fisetin, quercetin, morin, tricetin, gossypetin, apigenin and myricetin were investigated on rat mesangial cells with lipopolysaccharide (LPS) as the inflammatory stimuli. 6-Hydroxyflavone and 4′,6-dihydroxyflavone exhibited high activity with IC50 in the range of 2.0 μM, a much better inhibition potential in comparison to the well-studied polyhydroxylated flavones. Interestingly, the anti-inflammatory activity was not due to direct quenching of NO radicals. Investigation on derivatives with methylation, acetylation or sulfation of 6-hydroxyl group revealed that 6-methoxyflavone was the …

Grunt Variation In The Oyster Toadfish Opsanus Tau: Effect Of Size And Sex, Michael L. Fine, Tyler D. Waybright

Biology Publications

As in insects, frogs and birds, vocal activity in fishes tends to be more developed in males than in females, and sonic swimbladder muscles may be sexually dimorphic, i.e., either larger in males or present only in males. Male oyster toadfish Opsanus tau L produce a long duration, tonal boatwhistle advertisement call, and both sexes grunt, a short duration more pulsatile agonistic call. Sonic muscles are present in both sexes but larger in males. We tested the hypothesis that males would call more than females by inducing grunts in toadfish of various sizes held in a net and determined incidence …

Consequences Of Life History Switch Point Plasticity For Juvenile Morphology And Locomotion In The Túngara Frog, Julie Charbonnier, James R. Vonesh

Biology Publications

Many animals with complex life cycles can cope with environmental uncertainty by altering the timing of life history switch points through plasticity. Pond hydroperiod has important consequences for the fitness of aquatic organisms and many taxa alter the timing of life history switch points in response to habitat desiccation. For example, larval amphibians can metamorphose early to escape drying ponds. Such plasticity may induce variation in size and morphology of juveniles which can result in carry-over effects on jumping performance. To investigate the carry-over effects of metamorphic plasticity to pond drying, we studied the Túngara frog, Physalaemus pustulosus, a …

Identification Of Eastern United States Reticulitermes Termite Species Via Pcr-Rflp, Assessed Using Training And Test Data, Ryan C. Garrick, Benjamin D. Collins, Rachel N. Yi, Rodney J. Dyer, Chaz Hyseni

Biology Publications

Reticulitermes termites play key roles in dead wood decomposition and nutrient cycling in forests. They also damage man-made structures, resulting in considerable economic loss. In the eastern United States, five species (R. flavipes, R. virginicus, R. nelsonae, R. hageni and R. malletei) have overlapping ranges and are difficult to distinguish morphologically. Here we present a molecular tool for species identification. It is based on polymerase chain reaction (PCR) amplification of a section of the mitochondrial cytochrome oxidase subunit II gene, followed by a three-enzyme restriction fragment length polymorphism (RFLP) assay, with banding patterns resolved via agarose gel electrophoresis. The assay …

Hispanic Subgroups, Acculturation, And Substance Abuse Treatment Outcomes, Karen G. Chartier, Tom Carmody, Maleeha Akhtar, Mary B. Stebbins, Scott T. Walters, Diane Warden

Social Work Publications

This study explored Hispanic subgroup differences in substance use treatment outcomes, and the relationship of acculturation characteristics to these outcomes. Data were from a multisite randomized clinical trial of motivational enhancement therapy versus treatment as usual in a sample of Spanish-speaking substance abusers. Participants were Cuban American (n = 34), Mexican American (n = 209), Puerto Rican (n = 78), and other Hispanic American (n = 54). Results suggested that Cuban Americans and individuals with more connection to Hispanic culture had lower treatment retention. Hispanics born in the U.S and those who spoke English at home …

Comorbidities And Race/Ethnicity Among Adults With Stimulant Use Disorders In Residential Treatment, Katherine Sanchez, Karen G. Chartier, Tracy L. Greer, Robrina Walker, Thomas Carmody, Chad D. Rethorst

Social Work Publications

Comorbid physical and mental health problems are associated with poorer substance abuse treatment outcomes; however, little is known about these conditions among stimulant abusers at treatment entry. This study compared racial and ethnic groups on baseline measures of drug use patterns, comorbid physical and mental health disorders, quality of life, and daily functioning among cocaine and stimulant abusing/dependent patients. Baseline data from a multi-site randomized clinical trial of vigorous exercise as a treatment strategy for a diverse population of stimulant abusers (N = 290) were analyzed. Significant differences between groups were found on drug use characteristics, stimulant use disorders, …

Principal Component Analysis And Optimization: A Tutorial, Robert Reris, J. Paul Brooks

Statistical Sciences and Operations Research Publications

No abstract provided.

Protein Complexes In Bacteria, J. Harry Caufield, Marco Abreu, Christopher Wimble, Peter Uetz

Study of Biological Complexity Publications

Large-scale analyses of protein complexes have recently become available for Escherichia coli and Mycoplasma pneumoniae, yielding 443 and 116 heteromultimeric soluble protein complexes, respectively. We have coupled the results of these mass spectrometrycharacterized protein complexes with the 285 “gold standard” protein complexes identified by EcoCyc. A comparison with databases of gene orthology, conservation, and essentiality identified proteins conserved or lost in complexes of other species. For instance, of 285 “gold standard” protein complexes in E. coli, less than 10% are fully conserved among a set of 7 distantly-related bacterial “model” species. Complex conservation follows one of three models: well-conserved complexes, …

Pectoral Sound Generation In The Blue Catfish Ictalurus Furcatus, Yasha Mohajer, Zachary Ghahramani, Michael L. Fine

Forensic Science Publications

Catfishes produce pectoral stridulatory sounds by “jerk” movements that rub ridges on the dorsal process against the cleithrum. We recorded sound synchronized with high-speed video to investigate the hypothesis that blue catfish Ictalurus furcatus produce sounds by a slip–stick mechanism, previously described only in invertebrates. Blue catfish produce a variably paced series of sound pulses during abduction sweeps (pulsers) although some individuals (sliders) form longer duration sound units (slides) interspersed with pulses. Typical pulser sounds are evoked by short 1–2 ms movements with a rotation of 2°–3°. Jerks excite sounds that increase in amplitude after motion stops, suggesting constructive interference, …

Proteomics: In Pursuit Of Effective Traumatic Brain Injury Therapeutics, Pavel N. Lizhnyak, Andrew K. Ottens

Anatomy and Neurobiology Publications

Effective traumatic brain injury (TBI) therapeutics remain stubbornly elusive. Efforts in the field have been challenged by the heterogeneity of clinical TBI, with greater complexity among underlying molecular phenotypes than initially conceived. Future research must confront the multitude of factors comprising this heterogeneity, representing a big data challenge befitting the coming informatics age. Proteomics is poised to serve a central role in prescriptive therapeutic development, as it offers an efficient endpoint within which to assess post-TBI biochemistry. We examine rationale for multifactor TBI proteomic studies and the particular importance of temporal profiling in defining biochemical sequences and guiding therapeutic development. …

Identification Of Small-Molecule Inhibitors Against Meso-2, 6-Diaminopimelate Dehydrogenase From Porphyromonas Gingivalis, Victoria N. Stone, Hardik I. Parikh, Fadi El-Rami, Xiuchun Ge, Weihau Chen, Yan Zhang, Glen E. Kellogg, Ping Xu

Philips Institute for Oral Health Research Publications

Species-specific antimicrobial therapy has the potential to combat the increasing threat of antibiotic resistance and alteration of the human microbiome. We therefore set out to demonstrate the beginning of a pathogen-selective drug discovery method using the periodontal pathogen Porphyromonas gingivalis as a model. Through our knowledge of metabolic networks and essential genes we identified a “druggable” essential target, meso-diaminopimelate dehydrogenase, which is found in a limited number of species. We adopted a high-throughput virtual screen method on the ZINC chemical library to select a group of potential small-molecule inhibitors. Meso-diaminopimelate dehydrogenase from P. gingivaliswas first expressed …

Lysophosphatidic Acid Up-Regulates Hexokinase Ii And Glycolysis To Promote Proliferation Of Ovarian Cancer Cells, Abir Mukherjee, Yibao Ma, Fang Yuan, Yongling Gong, Zhenyu Fang, Esraa M. Mohamed, Erika Berrios, Huanjie Shao, Xianjun Fang

Biochemistry and Molecular Biology Publications

Lysophosphatidic acid (LPA), a blood-borne lipid mediator, is present in elevated concentrations in ascites of ovarian cancer patients and other malignant effusions. LPA is a potent mitogen in cancer cells. The mechanism linking LPA signal to cancer cell proliferation is not well understood. Little is known about whether LPA affects glucose metabolism to accommodate rapid proliferation of cancer cells. Here we describe that in ovarian cancer cells, LPA enhances glycolytic rate and lactate efflux. A real time PCR-based miniarray showed that hexokinase II (HK2) was the most dramatically induced glycolytic gene to promote glycolysis in LPA-treated cells. Analysis of the …

Dual Action Of Mir-125b As A Tumor Suppressor And Oncomir-22 Promotes Prostate Cancer Tumorigenesis, William T. Budd, Sarah J. Seashols-Williams, Gene C. Clark, Danielle Weaver, Valerie Calvert, Emanuel Petricoin, Ema A. Dragoescu, Katherine O'Hanlon, Zendra E. Zehner

Biochemistry and Molecular Biology Publications

MicroRNAs (miRs) are a novel class of small RNA molecules, the dysregulation of which can contribute to cancer. A combinatorial approach was used to identify miRs that promote prostate cancer progression in a unique set of prostate cancer cell lines, which originate from the parental p69 cell line and extend to a highly tumorigenic/metastatic M12 subline. Together, these cell lines are thought to mimic prostate cancer progression in vivo. Previous network analysis and miR arrays suggested that the loss of hsa-miR-125b together with the overexpression of hsa-miR-22 could contribute to prostate tumorigenesis. The dysregulation of these two miRs was …

Dpy-17 And Mua-3 Interact For Connective Tissue-Like Tissue Integrity In Caenorhabditis Elegans: A Model For Marfan Syndrome, Pauline Fotopoulos, Jeongho Kim, Moonjung Hyun, Waiss Qamari, Inhwan Lee, Young-Jai You

Biochemistry and Molecular Biology Publications

mua-3 is a Caenorhabditis elegans homolog of the mammalian fibrillin1, a monogenic cause of Marfan syndrome. We identified a new mutation of mua-3 that carries an in-frame deletion of 131 amino acids in the extracellular domain, which allows the mutants to survive in a temperature-dependent manner; at the permissive temperature, the mutants grow normally without obvious phenotypes, but at the nonpermissive temperature, more than 90% die during the L4 molt due to internal organ detachment. Using the temperature-sensitive lethality, we performed unbiased genetic screens to isolate suppressors to find genetic interactors of MUA-3. From two independent screens, we isolated …

Dissection Of C. Elegans Behavioral Genetics In 3-D Environments, Namseop Kwon, Ara B. Hwang, Young-Jai You, Seung-Jae V. Lee, Jung Ho Je

Biochemistry and Molecular Biology Publications

The nematode Caenorhabditis elegans is a widely used model for genetic dissection of animal behaviors. Despite extensive technical advances in imaging methods, it remains challenging to visualize and quantify C. elegans behaviors in three-dimensional (3-D) natural environments. Here we developed an innovative 3-D imaging method that enables quantification of C. elegans behavior in 3-D environments. Furthermore, for the first time, we characterized 3-D-specific behavioral phenotypes of mutant worms that have defects in head movement or mechanosensation. This approach allowed us to reveal previously unknown functions of genes in behavioral regulation. We expect that our 3-D imaging method will facilitate new …

Network Modelling Reveals The Mechanism Underlying Colitis-Associated Colon Cancer And Identifies Novel Combinatorial Anti-Cancer Targets, Junyan Lu, Hanlin Zeng, Zhongjie Liang, Limin Chen, Liyi Zhang, Hao Zhang, Hong Liu, Hualiang Jiang, Bairong Shen, Ming Huang, Meiyu Geng, Sarah Spiegel, Cheng Luo

Biochemistry and Molecular Biology Publications

The connection between inflammation and tumourigenesis has been well established. However, the detailed molecular mechanism underlying inflammation-associated tumourigenesis remains unknown because this process involves a complex interplay between immune microenvironments and epithelial cells. To obtain a more systematic understanding of inflammation-associated tumourigenesis as well as to identify novel therapeutic approaches, we constructed a knowledge-based network describing the development of colitis-associated colon cancer (CAC) by integrating the extracellular microenvironment and intracellular signalling pathways. Dynamic simulations of the CAC network revealed a core network module, including P53, MDM2, and AKT, that may govern the malignant transformation of colon epithelial cells in a …

P. Falciparum And P. Vivax Epitope-Focused Vlps Elicit Sterile Immunity To Blood Stage Infections, David C. Whitacre, Diego A. Espinosa, Cory J. Peters, Joyce E. Jones, Amy E. Tucker, Darrell L. Peterson, Fidel P. Zavala, David R. Milich

Biochemistry and Molecular Biology Publications

In order to design P. falciparum preerythrocytic vaccine candidates, a library of circumsporozoite (CS) T and B cell epitopes displayed on the woodchuck hepatitis virus core antigen (WHcAg) VLP platform was produced. To test the protective efficacy of the WHcAg-CS VLPs, hybrid CS P. berghei/P. falciparum (Pb/Pf) sporozoites were used to challenge immunized mice. VLPs carrying 1 or 2 different CS repeat B cell epitopes and 3 VLPs carrying different CS non-repeat B cell epitopes elicited high levels of anti-insert antibodies (Abs). Whereas, VLPs carrying CS repeat B cell epitopes conferred 98% protection of the liver against …

Increased Eicosanoid Levels In The Sugen/Chronic Hypoxia Model Of Severe Pulmonary Hypertension, Aysar Al-Husseini, Dayanjan S. Wijesinghe, Laszlo Farkas, Donatas Kraskauskas, Jennifer I. Drake, Ben Van Tassel, Antonio Abbate, Charles E. Chalfant, Norbert F. Voelkel

Biochemistry and Molecular Biology Publications

Inflammation and altered immunity are recognized components of severe pulmonary arterial hypertension in human patients and in animal models of PAH. While eicosanoid metabolites of cyclooxygenase and lipoxygenase pathways have been identified in the lungs from pulmonary hypertensive animals their role in the pathogenesis of severe angioobliterative PAH has not been examined. Here we investigated whether a cyclooxygenase-2 (COX-2) inhibitor or diethylcarbamazine (DEC), that is known for its 5-lipoxygenase inhibiting and antioxidant actions, modify the development of PAH in the Sugen 5416/hypoxia (SuHx) rat model. The COX-2 inhibitor SC-58125 had little effect on the right ventricular pressure and did not …

Nanocuration Workflows: Establishing Best Practices For Identifying, Inputting, And Sharing Data To Inform Decisions On Nanomaterials, Christina M. Powers, Karmann A. Mills, Stephanie A. Morris, Fred Klaessig, Sharon Gaheen, Nastassja Lewinski, Christine Ogilvie Hendren

Chemical and Life Science Engineering Publications

There is a critical opportunity in the field of nanoscience to compare and integrate information across diverse fields of study through informatics (i.e., nanoinformatics). This paper is one in a series of articles on the data curation process in nanoinformatics (nanocuration). Other articles in this series discuss key aspects of nanocuration (temporal metadata, data completeness, database integration), while the focus of this article is on the nanocuration workflow, or the process of identifying, inputting, and reviewing nanomaterial data in a data repository. In particular, the article discusses: 1) the rationale and importance of a defined workflow in nanocuration, 2) the …

Generation Of Multicellular Tumor Spheroids With Microwell-Based Agarose Scaffolds For Drug Testing, Xue Gong, Chao Lin, Jian Cheng, Jiansheng Su, Hang Zhao, Tianlin Liu, Xuejun Wen, Peng Zhao

Chemical and Life Science Engineering Publications

Three dimensional multicellular aggregate, also referred to as cell spheroid or microtissue, is an indispensable tool for in vitro evaluating antitumor activity and drug efficacy. Compared with classical cellular monolayer, multicellular tumor spheroid (MCTS) offers a more rational platform to predict in vivo drug efficacy and toxicity. Nevertheless, traditional processing methods such as plastic dish culture with nonadhesive surfaces are regularly time-consuming, laborious and difficult to provide uniform-sized spheroids, thus causing poor reproducibility of experimental data and impeding high-throughput drug screening. In order to provide a robust and effective platform for in vitro drug evaluation, we present an agarose scaffold …

Genome-Scale Resources For Thermoanaerobacterium Saccharolyticum, Devin H. Currie, Babu Raman, Christopher M. Gowen, Timothy J. Tschaplinski, Miriam L. Land, Steven D. Brown, Sean F. Covalla, Dawn M. Klingeman, Zamin K. Yang, Nancy L. Engle, Courtney M. Johnson, Miguel Rodriguez, A Joe Shaw, William R. Kenealy, Lee R. Lynd, Stephen S. Fong, Jonathan R. Mielenz, Brian H. Davison, David A. Hogsett, Christopher D. Herring

Chemical and Life Science Engineering Publications

Background

Thermoanaerobacterium saccharolyticum is a hemicellulose-degrading thermophilic anaerobe that was previously engineered to produce ethanol at high yield. A major project was undertaken to develop this organism into an industrial biocatalyst, but the lack of genome information and resources were recognized early on as a key limitation.

Results

Here we present a set of genome-scale resources to enable the systems level investigation and development of this potentially important industrial organism. Resources include a complete genome sequence for strain JW/SL-YS485, a genome-scale reconstruction of metabolism, tiled microarray data showing transcription units, mRNA expression data from 71 different growth conditions or timepoints …

The Optimization And Comparison Of A Cerium Salt-Based Phosphate Filtration System To Industry Standard Phosphate Removal Water Filtration Systems, Nicholas Seymour, Snehi Shrestha, Laura Viktoria Pretzman

Capstone Design Expo Posters

Phosphorous, being one of the fundamental building blocks of life, has been linked with the increase of cyanobacteria and algae growth. One of the main ways that phosphorous enters the marine ecosystem is through the form of runoff phosphates from fertilizers and industrial processes. In addition to disrupting the biology of ecosystems another drawback of excess of phosphates is the tendency for these chemical groups to form scale buildup on metal through the form of calcium phosphate.

The goal of our project is to investigate a novel way of removing phosphate groups from wastewater with the use of the rare …

Non-Invasive Blood Glucose Monitoring System, Brittany Martinez, Brittany Noah, David Decker

Capstone Design Expo Posters

The objective of this project is to create a non-invasive hypoglycemic alert system that will detect a drop in blood sugar in type 1 diabetics during sleep. This will be achieved by creating an algorithm that couples heart rate variability with skin conductance to increase the accuracy of hypoglycemia detection. The device will be housed in a torso strap that will include: electrodes located over the user’s rib cage, a skin conductance sensor placed in the user’s armpit, a microcontroller to collect and process the data, and vibrating motors that will awaken the patient if hypoglycemia is detected. Integrating the …

Dynamics Of Planar Systems That Model Stage-Structured Populations, N. Lazaryan, Hassan Sedaghat

Mathematics and Applied Mathematics Publications

We study a general discrete planar system for modeling stage-structured populations. Our results include conditions for the global convergence of orbits to zero (extinction) when the parameters (vital rates) are time and density dependent. When the parameters are periodic we obtain weaker conditions for extinction. We also study a rational special case of the system for Beverton-Holt type interactions and show that the persistence equilibrium (in the positive quadrant) may be globally attracting even in the presence of interstage competition. However, we determine that with a sufficiently high level of competition, the persistence equilibrium becomes unstable (a saddle point) and …

Green Tea Inhibited The Elimination Of Nephro-Cardiovascular Toxins And Deteriorated The Renal Function In Rats With Renal Failure, Yu-Hsuan Peng, Douglas H. Sweet, Shiuan-Pey Lin, Chung-Ping Yu, Pei-Dawn Lee Chao, Yu-Chi Hou

Pharmaceutics Publications

Chronic kidney disease (CKD) is a major health problem worldwide. Indoxyl sulfate (IS) and p-cresyl sulfate (PCS) are highly protein-bound nephro-cardiovascular toxins, which are not efficiently removed through hemodialysis. The renal excretions of IS and PCS were mediated by organic anion transporters (OATs) such as OAT1 and OAT3. Green tea (GT) is a popular beverage containing plenty of catechins. Previous pharmacokinetic studies of teas have shown that the major molecules present in the bloodstream are the glucuronides/sulfates of tea catechins, which are putative substrates of OATs. Here we demonstrated that GT ingestion significantly elevated the systemic exposures of endogenous …

Analysis Of Standard Dna Procedures On Feathers Of Late 19th To Late 20th Century Osprey (Pandion Haliaetus), Alia A. Hamdan, Catherine B. Viverette, Rodney J. Dyer

Rice Rivers Center Research Symposium

Species with well-documented demographic histories and well known perturbations to gene flow provide good models for understanding how historic events impact contemporary population genetic structure1,2. Osprey (Pandion haliaetus), a marine bird-of-prey, experienced steep declines after widespread organochloride pesticide (e.g. DDT) use in the mid-twentieth century 3, however, population genetic consequences remain unknown. Use of historic specimens can aid population genetic studies4,5, however, these samples can degrade over time impacting quantity and quality of extracted DNA5. We compared the concentrations of extracted DNA of Osprey feathers from museum and research collections to those of contemporary samples collected according to standard field …

Communicating The Overall Experience Of Research Through Various Approaches Using Art: A Case Study Of The Prothonotary Warbler, Hannah Huddle, Lesley P. Bulluck, Sarah E. Faris

Rice Rivers Center Research Symposium

Recommended Citation

In general, scientific research has publication of data as the end goal. The process and experience, which are of great importance in art disciplines, is not necessarily represented or valued. However, science has an inherent element of art to it, which deserves to be shown. I have been studying Prothonotary Warblers with a team from the VCU Biology Department to learn how I can reinterpret the research in a way that bridges the gap between the experience and typical scientific products. The research team measured spatial and temporal variation in warbler prey abundance (caterpillars and mayflies) and assessed …

Emergent Non-Consumptive Predator Effects Alter Habitat Colonization By Mosquitoes, Ethan G. Staats, Salvatore J. Agosta, James R. Vonesh

Rice Rivers Center Research Symposium

Top-down consumptive control (suppression) is an important driver of populations and communities of prey organisms. Diverse predator assemblages often yield non-linear suppression with respect to constituent species' effects (emergence); most often diversity enhances suppression. Predators also affect prey organisms non-consumptively through changes in prey physiological, physical, spatial, temporal, and behavioral responses to predators. Role of predator diversity in non-consumptive response by prey is relatively un-studied. Role of predator diversity in shaping prey populations and communities through habitat colonization is a novel question.

Trail-Based High Throughput Screening Reveals A Link Between Trail-Mediated Apoptosis And Glutathione Reductase, A Key Component Of Oxidative Stress Response., Dmitri Rozanov, Anton Cheltsov, Eduard Sergienko, Stefan Vasile, Vladislav Golubkov, Alexander E Aleshin, Trevor Levin, Elie Traer, Byron Hann, Julia Freimuth, Nikita Alexeev, Max A Alekseyev, Sergey P Budko, Hans Peter Bächinger, Paul Spellman

Computational Biology Institute

A high throughput screen for compounds that induce TRAIL-mediated apoptosis identified ML100 as an active chemical probe, which potentiated TRAIL activity in prostate carcinoma PPC-1 and melanoma MDA-MB-435 cells. Follow-up in silico modeling and profiling in cell-based assays allowed us to identify NSC130362, pharmacophore analog of ML100 that induced 65-95% cytotoxicity in cancer cells and did not affect the viability of human primary hepatocytes. In agreement with the activation of the apoptotic pathway, both ML100 and NSC130362 synergistically with TRAIL induced caspase-3/7 activity in MDA-MB-435 cells. Subsequent affinity chromatography and inhibition studies convincingly demonstrated that glutathione reductase (GSR), a key …