Pharmacologic profiling of phosphoinositide 3-kinase inhibitors as mitigators of ionizing radiation-induced cell deaths

Journal of Pharmacology and Experimental Therapeutics

Volumn 347, Issue 3, 2013, Pages 669-680

  Lazo, John S ^a   Sharlow, Elizabeth R ^a   Epperly, Michael W ^b   Lira, Ana ^a   Leimgruber, Stephanie ^a   Skoda, Erin M ^c   Wipf, Peter ^c   Greenberger, Joel S ^b  

^a UNIVERSITY OF VIRGINIA   (United States)

^b UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

^c UNIVERSITY OF PITTSBURGH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 (1 CYANO 1 METHYLETHYL) 3 METHYL 8 (3 QUINOLINYL)IMIDAZO[4,5 C]QUINOLIN 2(1H,3H) ONE; 11 HYDROXY 4 (METHOXYMETHYL) 4A,6A DIMETHYL 2,7,10 TRIOXO 1 (PYRROLIDIN 1 YLMETHYLENE) 1,2,4,4A,5,6,6A,7,8,9,9A,10 DODECAHYDROINDENO[4,5 H]ISOCHROMEN 5 YL ACETATE; 2 MORPHOLINO 8 PHENYLCHROMONE; 2,4 DIFLUORO N [2 METHOXY 5 [4 (PYRIDAZIN 4 YL)QUINOLIN 6 YL]PYRIDIN 3 YL]BENZENESULFONAMIDE; AMIFOSTINE; CAPTOPRIL; CARBAMAZEPINE; CASPASE 3; CASPASE 7; CID 24798773; ENALAPRIL; GENISTEIN; GSK 2126458; HISTONE H2AX; IDELALISIB; JP 4 039; MEVINOLIN; OLTIPRAZ; PALBOCICLIB; PALOMID 529; PHENMETRAZINE; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3 KINASE INHIBITOR; PI 828; PRAVASTATIN; PX 867; RAMIPRIL; SIMVASTATIN; TETRACYCLINE; UNCLASSIFIED DRUG; UNINDEXED DRUG; XL 147;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CELL CYCLE CHECKPOINT; CELL CYCLE G1 PHASE; CELL CYCLE G2 PHASE; CELL CYCLE S PHASE; CELL DEATH; CELL SURVIVAL; CHEMICAL STRUCTURE; COMPUTER ANALYSIS; CONTROLLED STUDY; DNA DAMAGE; DRUG STRUCTURE; ENZYME ACTIVATION; GAMMA RADIATION; HUMAN; HUMAN CELL; IN VIVO STUDY; IONIZING RADIATION; LETHAL DOSE; MOUSE; NONHUMAN; PLURIPOTENT STEM CELL; PRIORITY JOURNAL; RADIATION DOSE; SINGLE DRUG DOSE;

ADULT; ANIMALS; BLOTTING, WESTERN; CASPASE 3; CASPASE 7; CELL DEATH; CELL DIVISION; CELL LINE, TUMOR; CELL MEMBRANE PERMEABILITY; CHROMONES; DNA DAMAGE; ENZYME INHIBITORS; FLOW CYTOMETRY; G1 PHASE; G2 PHASE; GAMMA RAYS; HUMANS; MALE; MICE; MICE, INBRED C57BL; MORPHOLINES; PHOSPHATIDYLINOSITOL 3-KINASES; RADIATION-PROTECTIVE AGENTS; S PHASE; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84887885240     PISSN: 00223565     EISSN: 15210103     Source Type: Journal    
DOI: 10.1124/jpet.113.208421     Document Type: Article

References (39)

1. Abraham RT (2001) Cell cycle checkpoint signaling through the ATM and ATR kinases. Genes Dev 15:2177-2196. (Pubitemid 32843830)
2. Brognard J, Clark AS, Ni Y, and Dennis PA (2001) Akt/protein kinase B is consti-tutively active in non-small cell lung cancer cells and promotes cellular survival and resistance to chemotherapy and radiation. Cancer Res 61:3986-3997. (Pubitemid 32720961)
3. Burdon T, Smith A, and Savatier P (2002) Signalling, cell cycle and pluripotency in embryonic stem cells. Trends Cell Biol 12:432-438. (Pubitemid 35239952)
4. Camps M, Rückle T, Ji H., Ardissone V, Rintelen F, Shaw J., Ferrandi C, Chabert C, Gillieron C., and Françon B, et al. (2005) Blockade of PI3Kg suppresses joint inflammation and damage in mouse models of rheumatoid arthritis. Nat Med 11: 936-943. (Pubitemid 41294438)
5. Citrin D, Cotrim AP, Hyodo F, Baum B.J., Krishna MC, and Mitchell JB (2010) Radioprotectors and mitigators of radiation-induced normal tissue injury. Oncologist 15:360-371.
6. Condliffe AM, Davidson K, Anderson K.E., Ellson CD, Crabbe T, Okkenhaug K, Vanhaesebroeck B., Turner M, Webb L, and Wymann MP, et al. (2005) Sequential activation of class IB and class IA PI3K is important for the primed respiratory burst of human but not murine neutrophils. Blood 106:1432-1440. (Pubitemid 41129612)
7. Courtney KD, Corcoran RB, and Engelman JA (2010) The PI3K pathway as drug target in human cancer. J Clin Oncol 28:1075-1083.
8. de la Peña L, Burgan WE, Carter DJ, Hollingshead MG, Satyamitra M, Camphausen K, and Tofilon PJ (2006) Inhibition of Akt by the alkylphospholipid perifosine does not enhance the radiosensitivity of human glioma cells. Mol Cancer Ther 5: 1504-1510. (Pubitemid 44070487)
9. Epperly MW, Franicola D, Shields D., Rwigema JC, Stone B, Zhang X, McBride W., Georges G, Wipf P, and Greenberger JS (2010) Screening of antimicrobial agents for in vitro radiation protection and mitigation capacity, including those used in supportive care regimens for bone marrow transplant recipients. In Vivo 24:9-19.
10. Firat E, Weyerbrock A, Gaedicke S., Grosu AL, and Niedermann G (2012) Chloro-quine or chloroquine-PI3K/Akt pathway inhibitor combinations strongly promote g-irradiation-induced cell death in primary stem-like glioma cells. PLoS ONE 7: e47357.
11. Gewirtz DA, Holt SE, and Elmore LW (2008) Accelerated senescence: an emerging role in tumor cell response to chemotherapy and radiation. Biochem Pharmacol 76: 947-957.
12. Gharbi SI, Zvelebil MJ, Shuttleworth S.J., Hancox T., Saghir N, Timms JF, and Waterfield MD (2007) Exploring the specificity of the PI3K family inhibitor LY294002. Biochem J 404:15-21. (Pubitemid 46788080)
13. Greenberger JS, Clump D, Kagan V., Bayir H, Lazo JS, Wipf P, Li S., Gao X, and Epperly MW (2011) Strategies for discovery of small molecule radiation protectors and radiation mitigators. Front Oncol 1:59.
14. Hall EJ and Giaccia AJ (2006) Radiobiology for the Radiologist, Lippincott Williams & Wilkins, Philadelphia, PA.
15. Iglesias-Bartolome R., Patel V, Cotrim A.P., Leelahavanichkul K., Molinolo AA, Mitchell JB, and Gutkind JS (2012) mTOR inhibition prevents epithelial stem cell senescence and protects from radiation-induced mucositis. Cell Stem Cell 11: 401-414.
16. Johnson SM, Torrice CD, Bell J.F., Monahan KB, Jiang Q, Wang Y, Ramsey M.R., Jin J., Wong KK, and Su L, et al (2010) Mitigation of hematologic radiation toxicity in mice through pharmacological quiescence induced by CDK4/6 inhibition. J Clin Invest 120:2528-2536.
17. Kim H, Bernard ME, Flickinger J, Epperly M.W., Wang H., Dixon TM, Shields D, Houghton F, Zhang X., and Greenberger JS (2011) The autophagy-inducing drug carbamazepine is a radiation protector and mitigator. Int J Radiat Biol 87: 1052-1060.
18. Kim SO, Bolton EE, and Bryant SH (2012) Effects of multiple conformers per compound upon 3-D similarity search and bioassay data analysis. J Cheminform 4:28.
19. Knight ZA, Gonzalez B, Feldman M.E., Zunder ER, Goldenberg DD, Williams O, Loewith R., Stokoe D, Balla A, and Toth B, et al. (2006) A pharmacological map of the PI3-K family defines a role for p110a in insulin signaling. Cell 125: 733-747.
20. Knight ZA, Lin H, and Shokat KM (2010) Targeting the cancer kinome through polypharmacology. Nat Rev Cancer 10:130-137.
21. Laplante M and Sabatini DM (2012) mTOR signaling in growth control and disease. Cell 149:274-293.
22. Liu P, Cheng H, Roberts T.M., and Zhao JJ (2009) Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov 8:627-644.
23. Ma C, Lazo JS, and Xie X-Q (2011) Compound acquisition and prioritization algorithm for constructing structurally diverse compound libraries. ACS Comb Sci 13: 223-231.
24. Mitchell GC, Fillinger JL, Sittadjody S, Avila J.L., Burd R., and Limesand KH (2010) IGF1 activates cell cycle arrest following irradiation by reducing binding of DNp63 to the p21 promoter. Cell Death Dis 1:e50.
25. Moulder JE, Cohen EP, and Fish BL (2011) Captopril and losartan for mitigation of renal injury caused by single-dose total-body irradiation. Radiat Res 175:29-36.
26. Olson CF (1995) Parallel algorithms for hierarchical clustering. Parallel Comput 21: 1313-1325 DOI: 10.1016/0167-8191(95)00017-I.
27. Rwigema JC, Beck B, Wang W., Doemling A, Epperly MW, Shields D, Goff J.P., Fra-nicola D, Dixon T, and Frantz MC, et al. (2011) Two strategies for the development of mitochondrion-targeted small molecule radiation damage mitigators. Int J Radiat Oncol Biol Phys 80:860-868.
28. Sharma A, Singh K, and Almasan A (2012) Histone H2AX phosphorylation: a marker for DNA damage. Methods Mol Biol 920:613-626.
29. Sokolov MV, Panyutin IV, Panyutin I.G., and Neumann RD (2011) Dynamics of the transcriptome response of cultured human embryonic stem cells to ionizing radiation exposure. Mutat Res 709-710:40-48.
30. Stanciu M, Wang Y, Kentor R., Burke N, Watkins S, Kress G., Reynolds I, Klann E, Angiolieri M.R., and Johnson JW, et al. (2000) Persistent activation of ERK contributes to glutamate-induced oxidative toxicity in a neuronal cell line and primary cortical neuron cultures. J Biol Chem 275:12200-12206. (Pubitemid 30237798)
31. Suman S, Johnson MD, Fornace A.J., Jr, and Datta K (2012) Exposure to ionizing radiation causes long-term increase in serum estradiol and activation of PI3K-Akt signaling pathway in mouse mammary gland. Int J Radiat Oncol Biol Phys 84: 500-507.
32. Thaker NG, McDonald PR, Zhang F, Kitchens C.A., Shun TY, Pollack IF, and Lazo JS (2010) Designing, optimizing, and implementing high-throughput siRNA genomic screening with glioma cells for the discovery of survival genes and novel drug targets. J Neurosci Methods 185:204-212.
33. Valerie K, Yacoub A, Hagan M.P., Curiel DT, Fisher PB, Grant S, and Dent P (2007) Radiation-induced cell signaling: inside-out and outside-in. Mol Cancer Ther 6: 789-801. (Pubitemid 46554549)
34. Viniegra JG, Martínez N, Modirassari P., Hernández Losa J, Parada Cobo C, Sán-chez-Arévalo Lobo VJ, Aceves Luquero CI, Alvarez-Vallina L, Ramón y Cajal S, and Rojas JM, et al. (2005) Full activation of PKB/Akt in response to insulin or ionizing radiation is mediated through ATM. J Biol Chem 280:4029-4036. (Pubitemid 40288566)
35. Wang XQ, Lui VC, Poon RTP, Lu P, and Poon RYC (2009) DNA damage mediated s and g(2) checkpoints in human embryonal carcinoma cells. Stem Cells 27:568-576.
36. Welsch ME, Snyder SA, and Stockwell BR (2010) Privileged scaffolds for library design and drug discovery. Curr Opin Chem Biol 14:347-361.
37. Wipf P and Halter RJ (2005) Chemistry and biology of wortmannin. Org Biomol Chem 3:2053-2061. (Pubitemid 40859876)
38. Wipf P, Minion DJ, Halter R.J., Berggren MI, Ho CB, Chiang GG, Kirkpatrick L, Abraham R., and Powis G (2004) Synthesis and biological evaluation of synthetic viridins derived from C(20)-heteroalkylation of the steroidal PI-3-kinase inhibitor wortmannin. Org Biomol Chem 2:1911-1920.
39. Zellefrow CD, Sharlow ER, Epperly M.W., Reese CE, Shun T, Lira A, Greenberger J.S., and Lazo JS (2012) Identification of druggable targets for radiation mitigation using a small interfering RNA screening assay. Radiat Res 178:150-159.