An Ultra High-Throughput, Whole-Animal Screen for Small Molecule Modulators of a Specific Genetic Pathway in Caenorhabditis elegans

PLoS ONE

Volumn 8, Issue 4, 2013, Pages

  Leung, Chi K ^a   Wang, Ying ^a   Malany, Siobhan ^b   Deonarine, Andrew ^a   Nguyen, Kevin ^b   Vasile, Stefan ^b   Choe, Keith P ^a  

^a UNIVERSITY OF FLORIDA   (United States)

^b BURNHAM INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACETOPHENONE DERIVATIVE; PHENYLMERCURIC ACETATE; PHLORETIN; PHLOROACETOPHENONE; TYRPHOSTIN; TYRPHOSTIN A9; TYRPHOSTIN AG879; UNCLASSIFIED DRUG; ACRYLAMIDE; CAENORHABDITIS ELEGANS PROTEIN; MOLECULAR LIBRARY; PHORBOL 13 ACETATE 12 MYRISTATE;

ARTICLE; CAENORHABDITIS ELEGANS; CONTROLLED STUDY; DRUG STRUCTURE; GENE; GENE CONTROL; GENE INDUCTION; HIGH THROUGHPUT SCREENING; IC 50; IN VIVO STUDY; MULTIDRUG RESISTANCE; NONHUMAN; PROCESS OPTIMIZATION; SKN 1 GENE; ANIMAL; DOSE RESPONSE; DRUG EFFECTS; DRUG SCREENING; DRUG STABILITY; GENE EXPRESSION REGULATION; GENETICS; HEAT SHOCK RESPONSE; METABOLISM; MOLECULAR LIBRARY; OXIDATIVE STRESS; PHARMACOLOGY; PHYSIOLOGY; PROCEDURES;

ANIMALIA; CAENORHABDITIS ELEGANS; NEMATODA;

ACRYLAMIDE; ANIMALS; CAENORHABDITIS ELEGANS; CAENORHABDITIS ELEGANS PROTEINS; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG EVALUATION, PRECLINICAL; DRUG STABILITY; GENE EXPRESSION REGULATION; HEAT-SHOCK RESPONSE; HIGH-THROUGHPUT SCREENING ASSAYS; OXIDATIVE STRESS; SMALL MOLECULE LIBRARIES; TETRADECANOYLPHORBOL ACETATE;

EID: 84876898289     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0062166     Document Type: Article

References (86)

1. Mayr LM, Bojanic D, (2009) Novel trends in high-throughput screening. Current Opinion in Pharmacology 9: 580-588.
2. Johnston PA, Foster CA, Tiemo MB, Shun TY, Shinde SN, et al. (2009) Cdc25B dual-specificity phosphatase inhibitors identified in a high-throughput screen of the NIH compound library. Assay and Drug Development Technologies 7: 250-265.
3. Fox JT, Myung K, (2012) Cell-based high-throughput screens for the discovery of chemotherapeutic agents. Oncotarget 3: 581-585.
4. Williams RG, Kandasamy R, Nickischer D, Trask OJ, Laethem C, et al. (2006) Generation and characterization of a stable MK2-EGFP cell line and subsequent development of a high-content imaging assay on the Cellomics ArrayScan platform to screen for p38 mitogen-activated protein kinase inhibitors. Measuring Biological Responses with Automated Microscopy 414: 364-389.
5. Gleeson P, Bravi G, Modi S, Lowe D, (2009) ADMET rules of thumb II: A comparison of the effects of common substituents on a range of ADMET parameters. Bioorg Med Chem 17: 5906-5919.
6. Bass AS, Cartwright ME, Mahon C, Morrison R, Snyder R, et al. (2009) Exploratory drug safety: a discovery strategy to reduce attrition in development. J Pharmacol Toxicol Methods 60: 69-78.
7. Gleeson MP, (2008) Generation of a set of simple, interpretable ADMET rules of thumb. J Med Chem 51: 817-834.
8. Roberts SA, (2001) High-throughput screening approaches for investigating drug metabolism and pharmacokinetics. Xenobiotica 31: 557-589.
9. Artal-Sanz M, de Jong L, Tavernarakis N, (2006) Caenorhabditis elegans: a versatile platform for drug discovery. Biotechnol J 1: 1405-1418.
10. Anastassopoulou CG, Fuchs BB, Mylonakis E, (2011) Caenorhabditis elegans-based model systems for antifungal drug discovery. Curr Pharm Des 17: 1225-1233.
11. Smout MJ, Kotze AC, McCarthy JS, Loukas A (2010) A novel high throughput assay for anthelmintic drug screening and resistance diagnosis by real-time monitoring of parasite motility. PLoS Negl Trop Dis 4.
12. Gosai SJ, Kwak JH, Luke CJ, Long OS, King DE, et al. (2010) Automated high-content live animal drug screening using C. elegans expressing the aggregation prone serpin alpha1-antitrypsin Z. PLoS One. 5: e15460.
13. Carroll PM, Dougherty B, Ross-Macdonald P, Browman K, FitzGerald K, (2003) Model systems in drug discovery: chemical genetics meets genomics. Pharmacology & Therapeutics 99: 183-220.
14. Wang Z, Sherwood DR, (2011) Dissection of genetic pathways in C. elegans. Caenorhabditis elegans: Molecular Genetics and Development, Second Edition 106: 113-157.
15. Yook K, Harris TW, Bieri T, Cabunoc A, Chan J, et al. (2012) WormBase 2012: more genomes, more data, new website. Nucleic Acids Res 40: D735-741.
16. Strange K, (2003) From genes to integrative physiology: Ion channel and transporter biology in Caenorhabditis elegans. Physiological Reviews 83: 377-415.
17. Antoshechkin I, Sternberg PW, (2007) The versatile worm: genetic and genomic resources for Caenorhabditis elegans research. Nature Reviews Genetics 8: 518-532.
18. Collins JJ, Evason K, Pickett CL, Schneider DL, Kornfeld K, (2008) The anticonvulsant ethosuximide disrupts sensory function to extend C. elegans lifespan. PLoS Genet 4: e1000230.
19. Marvanova M, Nichols CD, (2007) Identification of neuroprotective compounds of Caenorhabditis elegans dopaminergic neurons against 6-OHDA. J Mol Neurosci 31: 127-137.
20. Harrington AJ, Hamamichi S, Caldwell GA, Caldwell KA, (2010) C. elegans as a model organism to investigate molecular pathways involved with Parkinson's disease. Developmental Dynamics 239: 1282-1295.
21. Holden-Dye L, Crisford A, Welz C, von Samson-Himmelstjerna G, Walker RJ, et al. (2012) Worms take to the slo lane: a perspective on the mode of action of emodepside. Invertebrate Neuroscience 12: 29-36.
22. Jones AK, Buckingham SD, Sattelle DB, (2005) Chemistry-to-gene screens in Caenorhabditis elegans. Nature Reviews Drug Discovery 4: 321-330.
23. Katiki LM, Ferreira JFS, Zajac AM, Masler C, Lindsay DS, et al. (2011) Caenorhabditis elegans as a model to screen plant extracts and compounds as natural anthelmintics for veterinary use. Veterinary Parasitology 182: 264-268.
24. Geary TG, Thompson DP, (2001) Caenorhabditis elegans: how good a model for veterinary parasites? Veterinary Parasitology 101: 371-386.
25. Simpkin KG, Coles GC, (1981) The use of Caenorhabditis elegans for anthelmintic screening. Journal of Chemical Technology and Biotechnology 31: 66-69.
26. Abdulla MH, Ruelas DS, Wolff B, Snedecor J, Lim KC, et al. (2009) Drug discovery for Schistosomiasis: Hit and lead compounds identified in a library of known drugs by medium-throughput phenotypic screening. PLoS Negl Trop Dis 3: e478.
27. Sayed AA, Simeonov A, Thomas CJ, Inglese J, Austin CP, et al. (2008) Identification of oxadiazoles as new drug leads for the control of schistosomiasis. Nature Medicine 14: 407-412.
28. Kotze AC, Clifford S, O'Grady J, Behnke JM, McCarthy JS, (2004) An in vitro larval motility assay to determine anthelmintic sensitivity for human hookworm and Strongyloides species. American Journal of Tropical Medicine and Hygiene 71: 608-616.
29. Ellerbrock BR, Coscarelli EM, Gurney ME, Geary TG, (2004) Screening for presenilin inhibitors using the free-living nematode, Caenorhabditis elegans. Journal of Biomolecular Screening 9: 147-152.
30. Solis GM, Petrascheck M (2011) Measuring Caenorhabditis elegans life span in 96 well microtiter plates. J Vis Exp: pii: 2496.
31. Peters JU, Schnider P, Mattei P, Kansy M, (2009) Pharmacological promiscuity: dependence on compound properties and target specificity in a set of recent roche compounds. ChemMedChem 4: 680-686.
32. Castoreno AB, Eggert US, (2011) Small molecule probes of cellular pathways and networks. Acs Chem Biol 6: 86-94.
33. Praitis V, Maduro MF, (2011) Transgenesis in C. elegans. Caenorhabditis elegans: Molecular Genetics and Development, Second Edition 106: 161-185.
34. Hobert O, Loria P, (2006) Uses of GFP in Caenorhabditis elegans. Methods Biochem Anal 47: 203-226.
35. Jasmer DP, Goverse A, Smant G, (2003) Parasitic nematode interactions with mammals and plants. Annu Rev Phytopathol 41: 245-270.
36. Hotez P, (2009) Neglected diseases amid wealth in the United States and Europe. Health Aff (Millwood) 28: 1720-1725.
37. Chan MS, (1997) The global burden of intestinal nematode infections-fifty years on. Parasitol Today 13: 438-443.
38. Choe KP, Leung CK, Miyamoto MM, (2012) Unique structure and regulation of the nematode detoxification gene regulator, SKN-1: implications to understanding and controlling drug resistance. Drug Metab Rev 44: 209-223.
39. Persidis A, (1999) Cancer multidrug resistance. Nat Biotechnol 17: 94-95.
40. Prasad R, Panwar SL, (2002) Smriti (2002) Drug resistance in yeasts-an emerging scenario. Adv Microb Physiol 46: 155-201.
41. Moye-Rowley WS, (2003) Transcriptional control of multidrug resistance in the yeast Saccharomyces. Prog Nucleic Acid Res Mol Biol 73: 251-279.
42. Prasad R, Kapoor K, (2005) Multidrug resistance in yeast Candida. Int Rev Cytol 242: 215-248.
43. Sipos G, Kuchler K, (2006) Fungal ATP-binding cassette (ABC) transporters in drug resistance & detoxification. Curr Drug Targets 7: 471-481.
44. Lubelski J, Konings WN, Driessen AJ, (2007) Distribution and physiology of ABC-type transporters contributing to multidrug resistance in bacteria. Microbiol Mol Biol Rev 71: 463-476.
45. Sykiotis GP, Bohmann D, (2010) Stress-activated cap'n'collar transcription factors in aging and human disease. Sci Signal 3: re3.
46. Wang XJ, Sun Z, Villeneuve NF, Zhang S, Zhao F, et al. (2008) Nrf2 enhances resistance of cancer cells to chemotherapeutic drugs, the dark side of Nrf2. Carcinogenesis 29: 1235-1243.
47. Homma S, Ishii Y, Morishima Y, Yamadori T, Matsuno Y, et al. (2009) Nrf2 enhances cell proliferation and resistance to anticancer drugs in human lung cancer. Clinical Cancer Research 15: 3423-3432.
48. Liu QA, Zhang H, Smeester L, Zou F, Kesic M, et al. (2010) The NRF2-mediated oxidative stress response pathway is associated with tumor cell resistance to arsenic trioxide across the NCI-60 panel. Bmc Medical Genomics 3: 37.
49. Ma X, Zhang J, Liu S, Huang Y, Chen B, et al. (2012) Nrf2 knockdown by shRNA inhibits tumor growth and increases efficacy of chemotherapy in cervical cancer. Cancer Chemother Pharmacol 69: 485-494.
50. An JH, Blackwell TK, (2003) SKN-1 links C. elegans mesendodermal specification to a conserved oxidative stress response. Genes Dev 17: 1882-1893.
51. Oliveira RP, Porter Abate J, Dilks K, Landis J, Ashraf J, et al. (2009) Condition-adapted stress and longevity gene regulation by Caenorhabditis elegans SKN-1/Nrf. Aging Cell 8: 524-541.
52. Park SK, Tedesco PM, Johnson TE, (2009) Oxidative stress and longevity in Caenorhabditis elegans as mediated by SKN-1. Aging Cell 8: 258-269.
53. Bowerman B, Eaton BA, Priess JR, (1992) skn-1, a maternally expressed gene required to specify the fate of ventral blastomeres in the early C. elegans embryo. Cell 68: 1061-1075.
54. Choe KP, Przybysz AJ, Strange K, (2009) The WD40 repeat protein WDR-23 functions with the CUL4/DDB1 ubiquitin ligase to regulate nuclear abundance and activity of SKN-1 in Caenorhabditis elegans. Mol Cell Biol 29: 2704-2715.
55. Blackwell TK, Bowerman B, Priess JR, Weintraub H, (1994) Formation of a monomeric DNA binding domain by Skn-1 bZIP and homeodomain elements. Science 266: 621-628.
56. Leung CK, Deonarine A, Strange K, Choe KP (2011) High-throughput screening and biosensing with fluorescent C. elegans strains. J Vis Exp: e2754.
57. Brenner S, (1974) The genetics of Caenorhabditis elegans. Genetics 77: 71-94.
58. Przybysz AJ, Choe KP, Roberts LJ, Strange K, (2009) Increased age reduces DAF-16 and SKN-1 signaling and the hormetic response of Caenorhabditis elegans to the xenobiotic juglone. Mech Ageing Dev 130: 357-369.
59. Choe KP, Strange K, (2007) Evolutionarily conserved WNK and Ste20 kinases are essential for acute volume recovery and survival after hypertonic shrinkage in Caenorhabditis elegans. Am J Physiol Cell Physiol 293: C915-927.
60. Leung CK, Empinado H, Choe KP, (2012) Depletion of a nucleolar protein activates xenobiotic detoxification genes in Caenorhabditis elegans via Nrf/SKN-1 and p53/CEP-1. Free Radic Biol Med 52: 937-950.
61. Kahn NW, Rea SL, Moyle S, Kell A, Johnson TE, (2008) Proteasomal dysfunction activates the transcription factor SKN-1 and produces a selective oxidative-stress response in Caenorhabditis elegans. Biochem J 409: 205-213.
62. Hasegawa K, Miwa S, Isomura K, Tsutsumiuchi K, Taniguchi H, et al. (2008) Acrylamide-responsive genes in the nematode Caenorhabditis elegans. Toxicol Sci 101: 215-225.
63. Leiers BR, Kampkotter A, Grevelding CG, Link CD, Johnson TE, et al. (2003) A stress-responsive glutathione S-transferase confers resistance to oxidative stress in Caenorhabditis elegans. Free Radical Biology and Medicine 34: 1405-1415.
64. Aithal BK, Kumar MRS, Rao BN, Upadhya R, Prabhu V, et al. (2011) Evaluation of pharmacokinetic, biodistribution, pharmacodynamic, and toxicity profile of free juglone and its sterically stabilized liposomes. Journal of Pharmaceutical Sciences 100: 3517-3528.
65. Wright DA, Mitchelmore CL, Dawson R, Cutler HG, (2007) The influence of water quality on the toxicity and degradation of juglone (5-hydroxy 1,4-naphthoquinone). Environ Technol 28: 1091-1101.
66. Hasegawa K, Miwa S, Tsutsumiuchi K, Taniguchi H, Miwa J, (2004) Extremely low dose of acrylamide decreases lifespan in Caenorhabditis elegans. Toxicology Letters 152: 183-189.
67. Hasegawa K, Miwa J, (2010) Genetic and cellular characterization of Caenorhabditis elegans mutants abnormal in the regulation of many phase II enzymes. PLoS One 5: e11194.
68. Walker GA, Thompson FJ, Brawley A, Scanlon T, Devaney E, (2003) Heat shock factor functions at the convergence of the stress response and developmental pathways in Caenorhabditis elegans. FASEB Journal 17: 1960-1962.
69. Link CD, Cypser JR, Johnson CJ, Johnson TE, (1999) Direct observation of stress response in Caenorhabditis elegans using a reporter transgene. Cell Stress & Chaperones 4: 235-242.
70. Tullet JM, Hertweck M, An JH, Baker J, Hwang JY, et al. (2008) Direct inhibition of the longevity-promoting factor SKN-1 by insulin-like signaling in C. elegans. Cell 132: 1025-1038.
71. Lemmon MA, Schlessinger J, (2010) Cell signaling by receptor tyrosine kinases. Cell 141: 1117-1134.
72. Weyermann J, Lochmann D, Zimmer A, (2005) A practical note on the use of cytotoxicity assays. Int J Pharm 288: 369-376.
73. Sumantran VN, (2011) Cellular chemosensitivity assays: an overview. Methods Mol Biol 731: 219-236.
74. James CE, Davey MW, (2007) A rapid colorimetric assay for the quantitation of the viability of free-living larvae of nematodes in vitro. Parasitol Res 101: 975-980.
75. Mathiesen L, Malterud KE, Sund RB, (1997) Hydrogen bond formation as basis for radical scavenging activity: a structure-activity study of C-methylated dihydrochalcones from Myrica gale and structurally related acetophenones. Free Radic Biol Med 22: 307-311.
76. Oresajo C, Stephens T, Hino PD, Law RM, Yatskayer M, et al. (2008) Protective effects of a topical antioxidant mixture containing vitamin C, ferulic acid, and phloretin against ultraviolet-induced photodamage in human skin. J Cosmet Dermatol 7: 290-297.
77. Rezk BM, Haenen GR, van der Vijgh WJ, Bast A, (2002) The antioxidant activity of phloretin: the disclosure of a new antioxidant pharmacophore in flavonoids. Biochem Biophys Res Commun 295: 9-13.
78. Calliste CA, Le Bail JC, Trouillas P, Pouget C, Habrioux G, et al. (2001) Chalcones: structural requirements for antioxidant, estrogenic and antiproliferative activities. Anticancer Res 21: 3949-3956.
79. Aithal BK, Kumar MR, Rao BN, Udupa N, Rao BS, (2009) Juglone, a naphthoquinone from walnut, exerts cytotoxic and genotoxic effects against cultured melanoma tumor cells. Cell Biol Int 33: 1039-1049.
80. Rosse C, Linch M, Kermorgant S, Cameron AJM, Boeckeler K, et al. (2010) PKC and the control of localized signal dynamics. Nature Reviews Molecular Cell Biology 11: 103-112.
81. Kalive M, Faust JJ, Koeneman BA, Capco DG, (2010) Involvement of the PKC family in regulation of early development. Mol Reprod Dev 77: 95-104.
82. Basu A, Pal D, (2010) Two faces of protein kinase Cδ: the contrasting roles of PKCδ in cell survival and cell death. Scientific World Journal 10: 2272-2284.
83. Huang HC, Nguyen T, Pickett CB, (2002) Phosphorylation of Nrf2 at Ser-40 by protein kinase C regulates antioxidant response element-mediated transcription. Journal of Biological Chemistry 277: 42769-42774.
84. Huang HC, Nguyen T, Pickett CB, (2000) Regulation of the antioxidant response element by protein kinase C-mediated phosphorylation of NF-E2-related factor 2. Proc Natl Acad Sci U S A 97: 12475-12480.
85. Burns AR, Wallace IM, Wildenhain J, Tyers M, Giaever G, et al. (2010) A predictive model for drug bioaccumulation and bioactivity in Caenorhabditis elegans. Nat Chem Biol.
86. Partridge FA, Tearle AW, Gravato-Nobre MJ, Schafer WR, Hodgkin J, (2008) The C. elegans glycosyltransferase BUS-8 has two distinct and essential roles in epidermal morphogenesis. Dev Biol 317: 549-559.