Anti-Cancer Activity of a Novel Small Molecule Compound That Simultaneously Activates p53 and Inhibits NF-κB Signaling

PLoS ONE

Volumn 7, Issue 9, 2012, Pages

  Hwang, Sun Gwan ^a,b   Park, Jinah ^c   Park, Joo Young ^a   Park, Cheol Hyoung ^a   Lee, Ki Ho ^a   Cho, Jeong Woo ^a   Hwang, Jong Ik ^b   Seong, Jae Young ^b  

^a SK Biopharmaceuticals Co   (South Korea)

^b Korea University   (South Korea)

^c Korea Research Institute of Bioscience and Biotechnology (KRIBB)   (South Korea)

Author keywords

[No Author keywords available]

Indexed keywords

5 ETHYL 3 METHYL 6 (1 METHYL 1H PYRIDIN 2 YLIDENEMETHYL)PHENANTHRIDINIUM; AMINOACRIDINE; ANTINEOPLASTIC AGENT; GROWTH ARREST AND DNA DAMAGE INDUCIBLE PROTEIN 45; GROWTH ARREST AND DNA DAMAGE INDUCIBLE PROTEIN 45A; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 6; MEPACRINE; MONOCYTE CHEMOTACTIC PROTEIN 1; PROTEIN P21; PROTEIN P53; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER INHIBITION; CELL DEATH; CONTROLLED STUDY; DRUG IDENTIFICATION; GENE EXPRESSION; HUMAN; HUMAN CELL; IN VITRO STUDY; LUNG CARCINOMA; MELANOMA; MOUSE; NONHUMAN; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION;

ANIMALS; ANTINEOPLASTIC AGENTS; CELL LINE, TUMOR; CHEMOKINE CCL2; DRUG SCREENING ASSAYS, ANTITUMOR; GENE EXPRESSION REGULATION, NEOPLASTIC; GENE REGULATORY NETWORKS; HIGH-THROUGHPUT SCREENING ASSAYS; HUMANS; INTERLEUKIN-6; LETHAL DOSE 50; MICE; NF-KAPPA B; NITRIC OXIDE; PHENANTHRIDINES; PYRIDINES; SIGNAL TRANSDUCTION; SMALL MOLECULE LIBRARIES; STRESS, PHYSIOLOGICAL; TRANSCRIPTIONAL ACTIVATION; TRANSCRIPTOME; TUMOR SUPPRESSOR PROTEIN P53;

MURINAE;

EID: 84866394311     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0044259     Document Type: Article

References (58)

1. Sharma HW, Narayanan R, (1996) The NF-kappaB transcription factor in oncogenesis. Anticancer Res 16: 589-596.
2. Baeuerle PA, Baltimore D, (1996) NF-kappa B: ten years after. Cell 87: 13-20.
3. Mayo MW, Baldwin AS, (2000) The transcription factor NF-kappaB: control of oncogenesis and cancer therapy resistance. Biochim Biophys Acta 1470: M55-62.
4. Gilmore TD, Herscovitch M, (2006) Inhibitors of NF-kappaB signaling: 785 and counting. Oncogene 25: 6887-6899.
5. Brown CJ, Lain S, Verma CS, Fersht AR, Lane DP, (2009) Awakening guardian angels: drugging the p53 pathway. Nature Reviews Cancer 9: 862-873.
6. Bulavin DV, Saito S, Hollander MC, Sakaguchi K, Anderson CW, et al. (1999) Phosphorylation of human p53 by p38 kinase coordinates N-terminal phosphorylation and apoptosis in response to UV radiation. EMBO J 18: 6845-6854.
7. Rong J-J, Hu R, Song X-M, Ha J, Lu N, et al. (2010) Gambogic acid triggers DNA damage signaling that induces p53/p21Waf1/CIP1 activation through the ATR-Chk1 pathway. Cancer Letters 296: 55-64.
8. Chehab NH, Malikzay A, Stavridi ES, Halazonetis TD, (1999) Phosphorylation of Ser-20 mediates stabilization of human p53 in response to DNA damage. Proc Natl Acad Sci U S A 96: 13777-13782.
9. Shieh SY, Ikeda M, Taya Y, Prives C, (1997) DNA damage-induced phosphorylation of p53 alleviates inhibition by MDM2. Cell 91: 325-334.
10. Sakamoto K, Maeda S, (2010) Targeting NF-kappaB for colorectal cancer. Expert Opin Ther Targets 14: 593-601.
11. Basseres DS, Baldwin AS, (2006) Nuclear factor-kappaB and inhibitor of kappaB kinase pathways in oncogenic initiation and progression. Oncogene 25: 6817-6830.
12. Prasad S, Ravindran J, Aggarwal BB, (2010) NF-kappaB and cancer: how intimate is this relationship. Mol Cell Biochem 336: 25-37.
13. Zhou J, Zhang H, Gu P, Bai J, Margolick JB, et al. (2007) NF-κB pathway inhibitors preferentially inhibit breast cancer stem-like cells. Breast Cancer Research and Treatment 111: 419-427.
14. Gilbert LA, Hemann MT, (2010) DNA damage-mediated induction of a chemoresistant niche. Cell 143: 355-366.
15. Iliopoulos D, Hirsch HA, Struhl K, (2009) An epigenetic switch involving NF-kappaB, Lin28, Let-7 MicroRNA, and IL6 links inflammation to cell transformation. Cell 139: 693-706.
16. Wang Y, Niu XL, Qu Y, Wu J, Zhu YQ, et al. (2010) Autocrine production of interleukin-6 confers cisplatin and paclitaxel resistance in ovarian cancer cells. Cancer Lett 295: 110-123.
17. Herbst RS, Heymach JV, Lippman SM, (2008) Lung cancer. N Engl J Med 359: 1367-1380.
18. Barbie DA, Tamayo P, Boehm JS, Kim SY, Moody SE, et al. (2009) Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1. Nature 462: 108-112.
19. Meylan E, Dooley AL, Feldser DM, Shen L, Turk E, et al. (2009) Requirement for NF-κB signalling in a mouse model of lung adenocarcinoma. Nature 462: 104-107.
20. Finco TS, Westwick JK, Norris JL, Beg AA, Der CJ, et al. (1997) Oncogenic Ha-Ras-induced signaling activates NF-kappaB transcriptional activity, which is required for cellular transformation. J Biol Chem 272: 24113-24116.
21. Min J, Zaslavsky A, Fedele G, McLaughlin SK, Reczek EE, et al. (2010) An oncogene-tumor suppressor cascade drives metastatic prostate cancer by coordinately activating Ras and nuclear factor-kappaB. Nat Med 16: 286-294.
22. Blaydes JP, Wynford-Thomas D, (1998) The proliferation of normal human fibroblasts is dependent upon negative regulation of p53 function by mdm2. Oncogene 16: 3317-3322.
23. Vassilev LT, Vu BT, Graves B, Carvajal D, Podlaski F, et al. (2004) In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science 303: 844-848.
24. Issaeva N, Bozko P, Enge M, Protopopova M, Verhoef LG, et al. (2004) Small molecule RITA binds to p53, blocks p53-HDM-2 interaction and activates p53 function in tumors. Nat Med 10: 1321-1328.
25. Gu H, Wang X, Rao S, Wang J, Zhao J, et al. (2008) Gambogic acid mediates apoptosis as a p53 inducer through down-regulation of mdm2 in wild-type p53-expressing cancer cells. Molecular Cancer Therapeutics 7: 3298-3305.
26. Junttila MR, Karnezis AN, Garcia D, Madriles F, Kortlever RM, et al. (2010) Selective activation of p53-mediated tumour suppression in high-grade tumours. Nature 468: 567-571.
27. Feldser DM, Kostova KK, Winslow MM, Taylor SE, Cashman C, et al. (2010) Stage-specific sensitivity to p53 restoration during lung cancer progression. Nature 468: 572-575.
28. McCarthy N, (2011) Tumour suppressors: Selective justice. Nat Rev Cancer 11: 4.
29. Dey A, Tergaonkar V, Lane DP, (2008) Double-edged swords as cancer therapeutics: simultaneously targeting p53 and NF-kappaB pathways. Nat Rev Drug Discov 7: 1031-1040.
30. Wuerzberger-Davis SM, Nakamura Y, Seufzer BJ, Miyamoto S, (2007) NF-kappaB activation by combinations of NEMO SUMOylation and ATM activation stresses in the absence of DNA damage. Oncogene 26: 641-651.
31. Dey A, Wong ET, Cheok CF, Tergaonkar V, Lane DP, (2008) R-Roscovitine simultaneously targets both the p53 and NF-kappaB pathways and causes potentiation of apoptosis: implications in cancer therapy. Cell Death Differ 15: 263-273.
32. Gurova KV, (2005) Small molecules that reactivate p53 in renal cell carcinoma reveal a NF- B-dependent mechanism of p53 suppression in tumors. Proceedings of the National Academy of Sciences 102: 17448-17453.
33. Wang W, Ho WC, Dicker DT, MacKinnon C, Winkler JD, et al. (2005) Acridine derivatives activate p53 and induce tumor cell death through Bax. Cancer Biol Ther 4: 893-898.
34. Lu W, Chen L, Peng Y, Chen J, (2001) Activation of p53 by roscovitine-mediated suppression of MDM2 expression. Oncogene 20: 3206-3216.
35. Bork PM, Schmitz ML, Kuhnt M, Escher C, Heinrich M, (1997) Sesquiterpene lactone containing Mexican Indian medicinal plants and pure sesquiterpene lactones as potent inhibitors of transcription factor NF-kappaB. FEBS Lett 402: 85-90.
36. Guzman ML, Rossi RM, Karnischky L, Li X, Peterson DR, et al. (2005) The sesquiterpene lactone parthenolide induces apoptosis of human acute myelogenous leukemia stem and progenitor cells. Blood 105: 4163-4169.
37. Sohn TA, Bansal R, Su GH, Murphy KM, Kern SE, (2002) High-throughput measurement of the Tp53 response to anticancer drugs and random compounds using a stably integrated Tp53-responsive luciferase reporter. Carcinogenesis 23: 949-957.
38. Raj L, Ide T, Gurkar AU, Foley M, Schenone M, et al. (2011) Selective killing of cancer cells by a small molecule targeting the stress response to ROS. Nature 475: 231-234.
39. Jones E, Adcock IM, Ahmed BY, Punchard NA, (2007) Modulation of LPS stimulated NF-kappaB mediated Nitric Oxide production by PKCepsilon and JAK2 in RAW macrophages. J Inflamm (Lond) 4: 23.
40. de Lange J, Ly LV, Lodder K, Verlaan-de Vries M, Teunisse AF, et al. (2012) Synergistic growth inhibition based on small-molecule p53 activation as treatment for intraocular melanoma. Oncogene 31: 1105-1116.
41. Basseres DS, Ebbs A, Levantini E, Baldwin AS, (2010) Requirement of the NF- B Subunit p65/RelA for K-Ras-Induced Lung Tumorigenesis. Cancer Research 70: 3537-3546.
42. Xia Y, Yeddula N, Leblanc M, Ke E, Zhang Y, et al. (2012) Reduced cell proliferation by IKK2 depletion in a mouse lung-cancer model. Nat Cell Biol.
43. Jiang Y, Cui L, Yie TA, Rom WN, Cheng H, et al. (2001) Inhibition of anchorage-independent growth and lung metastasis of A549 lung carcinoma cells by IkappaBbeta. Oncogene 20: 2254-2263.
44. Colburn NH, Bruegge WF, Bates JR, Gray RH, Rossen JD, et al. (1978) Correlation of anchorage-independent growth with tumorigenicity of chemically transformed mouse epidermal cells. Cancer Res 38: 624-634.
45. Liu G, Park YJ, Tsuruta Y, Lorne E, Abraham E, (2009) p53 Attenuates lipopolysaccharide-induced NF-kappaB activation and acute lung injury. J Immunol 182: 5063-5071.
46. Raj L, Ide T, Gurkar AU, Foley M, Schenone M, et al. (2011) Selective killing of cancer cells by a small molecule targeting the stress response to ROS. Nature 475: 231-234.
47. Gasparian AV, Burkhart CA, Purmal AA, Brodsky L, Pal M, et al. (2011) Curaxins: anticancer compounds that simultaneously suppress NF-kappaB and activate p53 by targeting FACT. Sci Transl Med 3: 95ra74.
48. Chenette EJ, (2009) Cancer: A Ras and NF-κB pas de deux. Nature Reviews Drug Discovery 8: 932-933.
49. Saha MN, Jiang H, Yang Y, Zhu X, Wang X, et al. (2012) Targeting p53 via JNK pathway: a novel role of RITA for apoptotic signaling in multiple myeloma. PLoS One 7: e30215.
50. Oyadomari S, Mori M, (2004) Roles of CHOP/GADD153 in endoplasmic reticulum stress. Cell Death Differ 11: 381-389.
51. Sofer A, Lei K, Johannessen CM, Ellisen LW, (2005) Regulation of mTOR and cell growth in response to energy stress by REDD1. Mol Cell Biol 25: 5834-5845.
52. Budanov AV, Karin M, (2008) p53 Target Genes Sestrin1 and Sestrin2 Connect Genotoxic Stress and mTOR Signaling. Cell 134: 451-460.
53. Saha MN, Jiang H, Mukai A, Chang H, (2010) RITA inhibits multiple myeloma cell growth through induction of p53-mediated caspase-dependent apoptosis and synergistically enhances nutlin-induced cytotoxic responses. Mol Cancer Ther 9: 3041-3051.
54. Sizemore N, Lerner N, Dombrowski N, Sakurai H, Stark GR, (2002) Distinct roles of the Ikappa B kinase alpha and beta subunits in liberating nuclear factor kappa B (NF-kappa B) from Ikappa B and in phosphorylating the p65 subunit of NF-kappa B. J Biol Chem 277: 3863-3869.
55. Shaw RJ, Cantley LC, (2006) Ras, PI(3)K and mTOR signalling controls tumour cell growth. Nature 441: 424-430.
56. Xie S, Wang Q, Wu H, Cogswell J, Lu L, et al. (2001) Reactive oxygen species-induced phosphorylation of p53 on serine 20 is mediated in part by polo-like kinase-3. J Biol Chem 276: 36194-36199.
57. Bunz F, Dutriaux A, Lengauer C, Waldman T, Zhou S, et al. (1998) Requirement for p53 and p21 to sustain G2 arrest after DNA damage. Science 282: 1497-1501.
58. Hwang SG, Lee D, Kim J, Seo T, Choe J, (2002) Human papillomavirus type 16 E7 binds to E2F1 and activates E2F1-driven transcription in a retinoblastoma protein-independent manner. J Biol Chem 277: 2923-2930.