Phosphanegold(I) thiolates, Ph3PAu[SC(OR)=NC6H4Me-4] for R = Me, Et and iPr, induce apoptosis, cell cycle arrest and inhibit cell invasion of HT-29 colon cancer cells through modulation of the nuclear factor-κB activation pathway and ubiquitination

  • Kah Kooi Ooi
  • Chien Ing Yeo
  • Kok-Pian Ang
  • Abdah Md Akim
  • Yoke-Kqueen Cheah
  • Siti Nadiah Abdul Halim
  • Hoi-Ling Seng
  • Edward R. T. Tiekink
Original Paper

Abstract

The phosphanegold(I) carbonimidothioates, Ph3PAu{SC(OR)=NC6H4Me-4} for R = Me (1), Et (2) and iPr (3), feature linear P–Au–S coordination geometries and exhibit potent in vitro cytotoxicity against HT-29 colon cancer cells in both monolayer and multi-cellular spheroid models (e.g., IC50 = 11.9 ± 0.4 and 20.3 ± 0.3 μM for 2, respectively). Both intrinsic and extrinsic pathways of apoptosis are demonstrated by human apoptosis PCR array analysis, caspase activities, DNA fragmentation and cell apoptotic assays. Compounds 13 induce an extrinsic pathway that leads to down-regulation of NFκB. Compound 2 also exhibits an extrinsic apoptotic pathway involving the activation of both p53 and p73, whereas 3 activates p53 only. Lys48- and Lys63-linked polyubiquitination are also promoted by 13.

Graphical abstract

Each of cytotoxic Ph3PAu{SC(OR)=NC6H4Me-4}, for R = Me (1), Et (2) and iPr (3), induce an intrinsic apoptotic pathway as well as an extrinsic pathway leading to down-regulation of NFκB. Lys48- and Lys63-linked polyubiquitination are promoted by 13 and these are able to inhibit cell invasion and to suppress the activity of TrxR.

Keywords

Gold(I) compounds Carbonimidothioates Phosphanegold thiolates Apoptosis Nuclear factor-κB activation pathway 

Supplementary material

775_2015_1271_MOESM1_ESM.pdf (740 kb)
Supplementary material 1 (PDF 739 kb)

References

  1. 1.
    Díaz-Rubio E, Tabernero J, Gómez-España A, Massutí B, Sastre J, Chaves M, Abad A, Carrato A, Queralt B, Reina JJ, Maurel J, Gonzalez-Flores E, Aparicio J, Rivera F, Losa F, Aranda E (2007) J Clin Oncol 25:4224–4230. doi:10.1200/JCO.2006.09.8467 PubMedGoogle Scholar
  2. 2.
    Tredan O, Galmarini CM, Patel K, Tannock IF (2007) J Natl Cancer Inst 99:1441–1454. doi:10.1093/jnci/djm135 PubMedGoogle Scholar
  3. 3.
    Schulenburg A, Bramswig K, Herrmann H, Karlic H, Mirkina I, Hubmann R, Laffer S, Marian B, Shehata M, Krepler C, Pehamberger H, Grunt T, Jager U, Zielinski CC, Valent P (2010) Crit Rev Oncol Hematol 76:79–98. doi:10.1016/j.critrevonc.2010.01.001 PubMedGoogle Scholar
  4. 4.
    Karin M, Greten FR (2005) Nat Rev Immunol 5:749–759. doi:10.1038/nri1703 PubMedGoogle Scholar
  5. 5.
    Naugler WE, Karin M (2008) Curr Opin Genet Dev 18:19–26. doi:10.1016/j.gde.2008.01.020 PubMedCentralPubMedGoogle Scholar
  6. 6.
    Escarcega RO, Fuentes-Alexandro S, Garcia-Carrasco M, Gatica A, Zamora A (2007) Clin Oncol 19:154–161. doi:10.1016/J.Clon.2006.11.013 Google Scholar
  7. 7.
    Reddy KB, Nabha SM, Atanaskova N (2003) Cancer Metastasis Rev 22:395–403. doi:10.1023/A:1023781114568 PubMedGoogle Scholar
  8. 8.
    Testa JR, Bellacosa A (2001) Proc Natl Acad Sci USA 98:10983–10985. doi:10.1073/pnas.211430998 PubMedCentralPubMedGoogle Scholar
  9. 9.
    Lee R, Collins T (2001) Circ Res 88:262–264. doi:10.1161/01.RES.88.3.262 PubMedGoogle Scholar
  10. 10.
    Rayet B, Gélinas C (1999) Oncogene 18:6938–6947. doi:10.1038/sj.onc.1203221 PubMedGoogle Scholar
  11. 11.
    Richmond A (2002) Nat Rev Immunol 2:664–674. doi:10.1038/nri887 PubMedCentralPubMedGoogle Scholar
  12. 12.
    Nakanishi C, Toi M (2005) Nat Rev Cancer 5:297–309. doi:10.1038/nrc1588 PubMedGoogle Scholar
  13. 13.
    Mathas S, Lietz A, Janz M, Hinz M, Jundt F, Scheidereit C, Bommert K, Dorken B (2003) Blood 102:1028–1034. doi:10.1182/blood-2002-04-1154 PubMedGoogle Scholar
  14. 14.
    Teicher BA, Herman TS, Holden SA, Wang YY, Pfeffer MR, Crawford JW, Frei E III (1990) Science 247:1457–1461. doi:10.1126/science.2108497 PubMedGoogle Scholar
  15. 15.
    Desoize B, Jardillier J (2000) Crit Rev Oncol Hematol 36:193–207. doi:10.1016/S1040-8428(00)00086-X PubMedGoogle Scholar
  16. 16.
    Kang HG, Jenabi JM, Zhang J, Keshelava N, Shimada H, May WA, Ng T, Reynolds CP, Triche TJ, Sorensen PH (2007) Cancer Res 67:3094–3105. doi:10.1158/0008-5472.CAN-06-3259 PubMedCentralPubMedGoogle Scholar
  17. 17.
    Oktem G, Bilir A, Selvi N, Yurtseven ME, Vatansever S, Ates U, Uysal A, Omay SB (2006) Oncol Res 16:195–203. doi:10.3727/000000006783981107 PubMedGoogle Scholar
  18. 18.
    Reyes-Zurita FJ, Pachon-Pena G, Lizarraga D, Rufino-Palomares EE, Cascante M, Lupianez JA (2011) BMC Cancer 11:154. doi:10.1186/1471-2407-11-154 PubMedCentralPubMedGoogle Scholar
  19. 19.
    Berners-Price SJ, Filipovska A (2011) Metallomics 3:863–873. doi:10.1039/C1MT00062D PubMedGoogle Scholar
  20. 20.
    Ott I (2009) Coord Chem Rev 253:1670–1681. doi:10.1016/j.ccr.2009.02.019 Google Scholar
  21. 21.
    Nardon C, Schmitt SM, Yang HJ, Zuo J, Fregona D, Dou QP (2014) PLoS One 9:e84248. doi:10.1371/journal.pone.0084248 PubMedCentralPubMedGoogle Scholar
  22. 22.
    Yeo CI, Ooi KK, Md Akim A, Ang KP, Fairuz ZA, Halim SNA, Ng SW, Seng HL, Tiekink ERT (2013) J Inorg Biochem 127:24–38. doi:10.1016/j.jinorgbio.2013.05.011 PubMedGoogle Scholar
  23. 23.
    Yeo CI, Sim JH, Khoo CH, Goh ZJ, Ang KP, Cheah YK, Fairuz ZA, Halim SNA, Ng SW, Seng HL, Tiekink ERT (2013) Gold Bull 46:145–152. doi:10.1007/s13404-013-0091-z Google Scholar
  24. 24.
    X’Pert HighScore Plus (2009) PANalytical B.V., Almelo, The NetherlandsGoogle Scholar
  25. 25.
    Kuan FS, Ho SY, Tadbuppa PP, Tiekink ERT (2008) CrystEngComm 10:548–564. doi:10.1039/b717198f Google Scholar
  26. 26.
    Tadbuppa PP, Tiekink ERT (2009) Acta Crystallogr E65:m1587. doi:10.1107/S1600536809047618 Google Scholar
  27. 27.
    Elmore S (2007) Toxicol Pathol 35:495–516. doi:10.1080/01926230701320337 PubMedCentralPubMedGoogle Scholar
  28. 28.
    Enari M, Sakahira H, Yokoyama H, Okawa K, Iwamatsu A, Nagata S (1998) Nature 391:43–50. doi:10.1038/34112 PubMedGoogle Scholar
  29. 29.
    Jackson SP, Bartek J (2009) Nature 461:1071–1078. doi:10.1038/nature08467 PubMedCentralPubMedGoogle Scholar
  30. 30.
    Abraham RT (2001) Genes Dev 15:2177–2196. doi:10.1101/gad.914401 PubMedGoogle Scholar
  31. 31.
    Gouvea LR, Garcia LS, Lachter DR, Nunes PR, de Castro Pereira F, Silveira-Lacerda EP, Louro SR, Barbeira PJ, Teixeira LR (2012) Eur J Med 55:67–73. doi:10.1016/j.ejmech.2012.07.004 Google Scholar
  32. 32.
    Oh HL, Lee DK, Lim H, Lee CH (2010) J Ethnopharmacol 129:135–139. doi:10.1016/j.jep.2010.02.010 PubMedGoogle Scholar
  33. 33.
    Cheng CC, Yang SM, Huang CY, Chen JC, Chang WM, Hsu SL (2005) Cancer Chemother Pharmacol 55:531–540. doi:10.1007/s00280-004-0919-6 PubMedGoogle Scholar
  34. 34.
    Nigg EA (1995) BioEssays 17:471–480. doi:10.1002/bies.950170603 PubMedGoogle Scholar
  35. 35.
    King RW, Jackson PK, Kirschner MW (1994) Cell 79:563–571. doi:10.1016/0092-8674(94)90542-8 PubMedGoogle Scholar
  36. 36.
    Krek W, Nigg EA (1991) EMBO J 10:305–316PubMedCentralPubMedGoogle Scholar
  37. 37.
    Jin P, Gu Y, Morgan DO (1996) J Cell Biol 134:963–970. doi:10.1083/jcb.134.4.963 PubMedGoogle Scholar
  38. 38.
    Grana X, Reddy EP (1995) Oncogene 11:211–219PubMedGoogle Scholar
  39. 39.
    Harper JW, Adami GR, Wei N, Keyomarsi K, Elledge SJ (1993) Cell 75:805–816. doi:10.1016/0092-8674(93)90499-G PubMedGoogle Scholar
  40. 40.
    Xiong Y, Hannon GJ, Zhang H, Casso D, Kobayashi R, Beach D (1993) Nature 366:701–704. doi:10.1038/366701a0 PubMedGoogle Scholar
  41. 41.
    Cho JH, Lee JG, Yang YI, Kim JH, Ahn JH, Baek NI, Lee KT, Choi JH (2011) Food Chem Toxicol 49:1737–1744. doi:10.1016/j.fct.2011.04.019 PubMedGoogle Scholar
  42. 42.
    Zhao R, Xiang N, Domann FE, Zhong W (2009) Nutr Cancer 61:397–407. doi:10.1080/01635580802582751 PubMedCentralPubMedGoogle Scholar
  43. 43.
    Baus F, Gire V, Fisher D, Piette J, Dulić V (2003) EMBO J22:3992–4002. doi:10.1093/emboj/cdg387 Google Scholar
  44. 44.
    Hsu YL, Kuo PL, Lin LT, Lin CC (2005) J Pharmacol Exp Ther 313:333–344. doi:10.1124/jpet.104.078808 PubMedGoogle Scholar
  45. 45.
    Abbas T, Dutta A (2009) Nat Rev Cancer 9:400–414. doi:10.1038/nrc2657 PubMedCentralPubMedGoogle Scholar
  46. 46.
    Ting NS, Lee WH (2004) DNA Repair 3:935–944. doi:10.1016/j.dnarep.2004.03.026 PubMedGoogle Scholar
  47. 47.
    Yarden RI, Pardo-Reoyo S, Sgagias M, Cowan KH, Brody LC (2002) Nat Genet 30:285–289. doi:10.1038/ng837 PubMedGoogle Scholar
  48. 48.
    Sorensen CS, Syljuasen RG (2012) Nucleic Acids Res 40:477–486. doi:10.1093/nar/gkr697 PubMedCentralPubMedGoogle Scholar
  49. 49.
    Takisawa H, Mimura S, Kubota Y (2000) Curr Opin Cell Biol 12:690–696. doi:10.1016/S0955-0674(00)00153-8 PubMedGoogle Scholar
  50. 50.
    Maiorano D, Lemaitre JM, Mechali M (2000) J Biol Chem 12:8426–8431. doi:10.1074/Jbc.275.12.8426 Google Scholar
  51. 51.
    Williams GH, Romanowski P, Morris LS, Madine M, Mills AD, Stoeber K, Marr J, Laskey RA, Coleman N (1998) Proc Natl Acad Sci USA 95:14932–14937. doi:10.1073/Pnas.95.25.14932 PubMedCentralPubMedGoogle Scholar
  52. 52.
    Stoeber K, Tlsty TD, Happerfield L, Thomas GA, Romanov S, Bobrow L, Williams ED, Williams GH (2001) J Cell Sci 114:2027–2041PubMedGoogle Scholar
  53. 53.
    Stoeber K, Halsall I, Freeman A, Swinn R, Doble A, Morris L, Coleman N, Bullock N, Laskey RA, Hales CN, Williams GH (1999) Lancet 354:1524–1525. doi:10.1016/S0140-6736(99)04265-8 PubMedGoogle Scholar
  54. 54.
    Rowinsky EK (2005) J Clin Oncol 23:9394–9407. doi:10.1200/Jco.2005.02.2889 PubMedGoogle Scholar
  55. 55.
    Fulda S, Debatin KM (2006) Oncogene 25:4798–4811. doi:10.1038/Sj.Onc.1209518 PubMedGoogle Scholar
  56. 56.
    Slee EA, O’Connor DJ, Lu X (2004) Oncogene 23:2809–2818. doi:10.1038/Sj.Onc.1207516 PubMedGoogle Scholar
  57. 57.
    Leung AW, Halestrap AP (2008) Biochim Biophys Acta 1777:946–952. doi:10.1016/j.bbabio.2008.03.009 PubMedGoogle Scholar
  58. 58.
    Ricchelli F, Sileikyté J, Bernardi P (2011) Biochim Biophys Acta 1807:482–490. doi:10.1016/j.bbabio.2011.02.012 PubMedGoogle Scholar
  59. 59.
    Skulachev VP (1996) FEBS Lett 397:7–10. doi:10.1016/0014-5793(96)00989-1 PubMedGoogle Scholar
  60. 60.
    Le Bras M, Clément MV, Pervaiz S, Brenner C (2005) Histo Histopathol 20:205–219. doi:10.1096/fj.05-5603rev Google Scholar
  61. 61.
    Chen F, Vallyathan V, Castranova V, Shi X (2001) Mol Cell Biochem 222:183–188. doi:10.1023/A:1017970330982 PubMedGoogle Scholar
  62. 62.
    LeBel CP, Ischiropoulos H, Bondy SC (1992) Chem Res Toxicol 5:227–231. doi:10.1021/tx00026a012 PubMedGoogle Scholar
  63. 63.
    Gomes A, Fernandes E, Lima JLFC (2005) J Biochem Biophys Meth 65:45–80. doi:10.1016/j.jbbm.2005.10.003 PubMedGoogle Scholar
  64. 64.
    Krammer PH (1999) Adv Immunol 71:163–210. doi:10.1016/S0065-2776(08)60402-2 PubMedGoogle Scholar
  65. 65.
    Hockenbery DM, Giedt CD, O’Neill JW, Manion MK, Banker DE (2002) Adv Cancer Res 85:203–242. doi:10.1016/S0065-230X(02)85007-2 PubMedGoogle Scholar
  66. 66.
    Henry-Mowatt J, Dive C, Martinou JC, James D (2004) Oncogene 23:2850–2860. doi:10.1038/sj.onc.1207534 PubMedGoogle Scholar
  67. 67.
    Yuan S, Yu X, Topf M, Ludtke SJ, Wang X, Akey CW (2010) Structure 18:571–583. doi:10.1016/j.str.2010.04.001 PubMedCentralPubMedGoogle Scholar
  68. 68.
    Lupidi G, Avenali L, Bramucci M, Quassinti L, Pettinari R, Khalife HK, Gali-Muhtasib H, Marchetti F, Pettinari C (2013) J Inorg Biochem 124:78–87. doi:10.1016/j.jinorgbio.2013.03.014 PubMedGoogle Scholar
  69. 69.
    Lakin ND, Jackson SP (1999) Oncogene 18:7644–7655. doi:10.1038/sj.onc.1203015 PubMedGoogle Scholar
  70. 70.
    Oda E, Ohki R, Murasawa H, Nemoto J, Shibue T, Yamashita T, Tokino T, Taniguchi T, Tanaka N (2000) Science 288:1053–1058. doi:10.1126/science.288.5468.1053 PubMedGoogle Scholar
  71. 71.
    Miyashita T, Reed JC (1995) Cell 80:293–299. doi:10.1016/0092-8674(95)90412-3 PubMedGoogle Scholar
  72. 72.
    Sax JK, Fei P, Murphy ME, Bernhard E, Korsmeyer SJ, El-Deiry WS (2002) Nat Cell Biol 4:842–849. doi:10.1038/ncb866 PubMedGoogle Scholar
  73. 73.
    Nakano K, Vousden KH (2001) Mol Cell 7:683–694. doi:10.1016/S1097-2765(01)00214-3 PubMedGoogle Scholar
  74. 74.
    Moll UM, Wolff S, Speidel D, Deppert W (2005) Curr Opin Cell Biol 17:631–636. doi:10.1016/j.ceb.2005.09.007 PubMedGoogle Scholar
  75. 75.
    Haupt S, Berger M, Goldberg Z, Haupt Y (2003) J Cell Sci 116:4077–4085. doi:10.1242/jcs.00739 PubMedGoogle Scholar
  76. 76.
    Milhas D, Cuvillier O, Therville N, Clave P, Thomsen M, Levade T, Benoist H, Segui B (2005) J Biol Chem 280:19836–19842. doi:10.1074/jbc.M414358200 PubMedGoogle Scholar
  77. 77.
    Abd El-Ghany RM, Sharaf NM, Kassem LA, Mahran LG, Heikal OA (2009) Drug Discov Ther 3:296–306. doi:10.1016/j.toxlet.2009.06.686 PubMedGoogle Scholar
  78. 78.
    Fulda S (2009) Cancer Lett 281:128–133. doi:10.1016/j.canlet.2008.11.023 PubMedGoogle Scholar
  79. 79.
    Yin XM (2006) Gene 369:7–19. doi:10.1016/j.gene.2005.10.038 PubMedGoogle Scholar
  80. 80.
    Dobbelstein M, Strano S, Roth J, Blandino G (2005) Biochem Biophys Res Commun 331:688–693. doi:10.1016/j.bbrc.2005.03.155 PubMedGoogle Scholar
  81. 81.
    Zhu J, Jiang J, Zhou W, Chen X (1998) Cancer Res 58:5061–5065PubMedGoogle Scholar
  82. 82.
    Takahashi H, Ichimiya S, Nimura Y, Watanabe M, Furusato M, Wakui S, Yatani R, Aizawa S, Nakagawara A (1998) Cancer Res 58:2076–2077. doi:10.1186/1471-2121-12-8 PubMedGoogle Scholar
  83. 83.
    Kovalev S, Marchenko N, Swendeman S, LaQuaglia M, Moll UM (1998) Cell Growth Differ 9:897–903PubMedGoogle Scholar
  84. 84.
    Irwin, Kondo K, Marin MC, Cheng LS, Hahn WC, Kaelin WG Jr (2003) Cancer Cell. doi:10.1016/S1535-6108(03)00078-3 PubMedGoogle Scholar
  85. 85.
    Wertz IE, Dixit VM (2008) Cytokine Growth Factor Rev 19:313–324. doi:10.1016/j.cytogfr.2008.04.014 PubMedGoogle Scholar
  86. 86.
    Karin M (2006) Nature 441:431–436. doi:10.1038/nature04870 PubMedGoogle Scholar
  87. 87.
    Song HY, Regnier CH, Kirschning CJ, Goeddel DV, Rothe M (1997) Proc Natl Acad Sci USA 94:9792–9796. doi:10.1073/pnas.94.18.9792 PubMedCentralPubMedGoogle Scholar
  88. 88.
    Ea CK, Deng L, Xia ZP, Pineda G, Chen ZJ (2006) Mol Cell 22:245–257. doi:10.1016/j.molcel.2006.03.026 PubMedGoogle Scholar
  89. 89.
    Deng L, Wang C, Spencer E, Yang L, Braun A, You J, Slaughter C, Pickart C, Chen ZJ (2000) Cell 103:351–361. doi:10.1016/S0092-8674(00)00126-4 PubMedGoogle Scholar
  90. 90.
    Hayden MS, Ghosh S (2004) Genes Dev 18:2195–2224. doi:10.1101/gad.1228704 PubMedGoogle Scholar
  91. 91.
    Shi Y, Xu P, Qin J (2011) Mol Cell Proteomics 10(R110):006882. doi:10.1074/mcp.R110.006882 PubMedGoogle Scholar
  92. 92.
    Fan Y, Shi Y, Liu S, Mao R, An L, Zhao Y, Zhang H, Zhang F, Xu G, Qin J, Yang J (2012) Cell Signal 24:1381–1389. doi:10.1016/j.cellsig.2012.02.017 PubMedCentralPubMedGoogle Scholar
  93. 93.
    Wertz IE, O’Rourke KM, Zhou H, Eby M, Aravind L, Seshagiri S, Wu P, Wiesmann C, Baker R, Boone DL, Ma A, Koonin EV, Dixit VM (2004) Nature 430:694–699. doi:10.1038/nature02794 PubMedGoogle Scholar
  94. 94.
    Kuo JC, Wang WJ, Yao CC, Wu PR, Chen RH (2006) J Cell Biol 172:619–631. doi:10.1083/jcb.200505138 PubMedCentralPubMedGoogle Scholar
  95. 95.
    Harrison B, Kraus M, Burch L, Stevens C, Craig A, Gordon-Weeks P, Hupp TR (2008) J Biol Chem 283:9999–10014. doi:10.1074/jbc.M706040200 PubMedGoogle Scholar
  96. 96.
    Yoo HJ, Byun HJ, Kim BR, Lee KH, Park SY, Rho SB (2012) Cell Signal 24:1471–1477. doi:10.1016/j.cellsig.2012.03.010 PubMedGoogle Scholar
  97. 97.
    Kodama N, Asakawa A, Inui A, Masuda Y, Nanba H (2005) Oncol Rep 13:497–502PubMedGoogle Scholar
  98. 98.
    Yang L, Cao Z, Yan H, Wood WC (2003) Cancer Res 63:6815–6824PubMedGoogle Scholar
  99. 99.
    LaCasse EC (2013) Cancer Lett 332:215–224. doi:10.1016/j.canlet.2012.06.015 PubMedGoogle Scholar
  100. 100.
    Nguyen DX, Massague J (2007) Nat Rev Genet 8:341–352. doi:10.1038/nrg2101 PubMedGoogle Scholar
  101. 101.
    Madani I, De Neve W, Mareel M (2008) Bull Cancer 95:292–300. doi:10.1684/bdc.2008.0598 PubMedGoogle Scholar
  102. 102.
    Tanei T, Morimoto K, Shimazu K, Kim SJ, Tanji Y, Taguchi T, Tamaki Y, Noguchi S (2009) Clin Cancer Res 15:4234–4241. doi:10.1158/1078-0432.CCR-08-1479 PubMedGoogle Scholar
  103. 103.
    Mehrotra S, Languino LR, Raskett CM, Mercurio AM, Dohi T, Altieri DC (2010) Cancer Cell 17:53–64. doi:10.1016/j.ccr.2009.11.021 PubMedCentralPubMedGoogle Scholar
  104. 104.
    Tan W, Zhang W, Strasner A, Grivennikov S, Cheng JQ, Hoffman RM, Karin M (2011) Nature 470:548–553. doi:10.1038/nature09707 PubMedCentralPubMedGoogle Scholar
  105. 105.
    Pikarsky E, Porat RM, Stein I, Abramovitch R, Amit S, Kasem S, Gutkovich-Pyest E, Urieli-Shoval S, Galun E, Ben-Neriah Y (2004) Nature 431:461–466. doi:10.1038/nature02924 PubMedGoogle Scholar
  106. 106.
    Wu Y, Deng J, Rychahou PG, Qiu S, Evers BM, Zhou BP (2009) Cancer Cell 15:416–428. doi:10.1016/j.ccr.2009.03.016 PubMedCentralPubMedGoogle Scholar
  107. 107.
    Park BK, Zhang H, Zeng Q, Dai J, Keller ET, Giordano T, Gu K, Shah V, Pei L, Zarbo RJ, McCauley L, Shi S, Chen S, Wang CY (2007) Nat Med 13:62–69. doi:10.1038/nm1519 PubMedGoogle Scholar

Copyright information

© SBIC 2015

Authors and Affiliations

  • Kah Kooi Ooi
    • 1
  • Chien Ing Yeo
    • 2
  • Kok-Pian Ang
    • 1
  • Abdah Md Akim
    • 1
  • Yoke-Kqueen Cheah
    • 1
  • Siti Nadiah Abdul Halim
    • 2
  • Hoi-Ling Seng
    • 1
    • 3
  • Edward R. T. Tiekink
    • 1
    • 2
  1. 1.Department of Biomedical Science, Faculty of Medicine and Health SciencesUniversity Putra Malaysia, UPMSerdangMalaysia
  2. 2.Department of ChemistryUniversity of MalayaKuala LumpurMalaysia
  3. 3.Department of Biological Sciences, Faculty of Science and TechnologySunway UniversityBandar SunwayMalaysia

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