Proapoptotic activity and chemosensitizing effect of the novel Akt inhibitor (2S)-1-(1H-indol-3-yl)-3-[5-(3-methyl-2H-indazol-5-yl)pyridin-3-yl] oxypropan2-amine (A443654) in T-cell acute lymphoblastic leukemia

Molecular Pharmacology

Volumn 74, Issue 3, 2008, Pages 884-895

  Falà, Federica ^a   Blalock, William L ^a   Tazzari, Pier Luigi ^b   Cappellini, Alessandra ^c   Chiarini, Francesca ^a   Martinelli, Giovanni ^a   Tafuri, Agostino ^d   McCubrey, James A ^e   Cocco, Lucio ^a   Martelli, Alberto M ^a  

^a UNIVERSITY OF BOLOGNA   (Italy)

^b UNIVERSITY OF BOLOGNA   (Italy)

^c UNIVERSITY OF CASSINO AND SOUTHERN LAZIO   (Italy)

^d SAPIENZA UNIVERSITY OF ROME   (Italy)

^e EAST CAROLINA UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 (1H INDOL 3 YL) 3 [5 (3 METHYL 2H INDAZOL 5 YL)PYRIDIN 3 YL]OXYPROPAN 2 AMINE; 2 (4 HYDROXYPHENYL) 4 MORPHOLINOPYRIDO[3',2':4,5]FURO[3,2 D]PYRIMIDINE; 2 MORPHOLINO 8 PHENYLCHROMONE; A443654; CASPASE 2; CASPASE 3; CASPASE 6; CASPASE 8; CASPASE 9; CASPASE INHIBITOR; ETOPOSIDE; GLYCOGEN SYNTHASE KINASE 3BETA; GLYCOPROTEIN P; PROTEIN KINASE B; PROTEIN KINASE B INHIBITOR; UNCLASSIFIED DRUG; WORTMANNIN;

ACUTE LYMPHOBLASTIC LEUKEMIA; APOPTOSIS; ARTICLE; CHROMOSOME 10; DRUG ACTIVITY; DRUG EFFICACY; DRUG MECHANISM; ENZYME ACTIVATION; ENZYME PHOSPHORYLATION; HUMAN; HUMAN CELL; LEUKEMIA CELL LINE; PRIORITY JOURNAL; PROTEIN DEPHOSPHORYLATION;

APOPTOSIS; CASPASES; CELL LINE, TUMOR; CELL PROLIFERATION; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG RESISTANCE, NEOPLASM; DRUG SCREENING ASSAYS, ANTITUMOR; DRUG SYNERGISM; ENZYME ACTIVATION; ETOPOSIDE; GLYCOGEN SYNTHASE KINASE 3; HUMANS; INDAZOLES; INDOLES; LEUKEMIA-LYMPHOMA, ADULT T-CELL; PHOSPHORYLATION; PHOSPHOSERINE; PHOSPHOTHREONINE; PROTO-ONCOGENE PROTEINS C-AKT;

EID: 50449097578     PISSN: 0026895X     EISSN: 15210111     Source Type: Journal    
DOI: 10.1124/mol.108.047639     Document Type: Article

References (37)

1. Bain J, Plater L, Elliott M, Shpiro N, Hastie CJ, McLauchlan H, Klevernic I, Arthur JS, Alessi DR, and Cohen P (2007) The selectivity of protein kinase inhibitors: a further update. Biochem J 408:297-315.
2. Blalock WL, Navolanic PM, Steelman LS, Shelton JG, Moye PW, Lee JT, Franklin RA, Mirza A, McMahon M, White MK, et al. (2003) Requirement for the PI3K/Akt pathway in MEK1-mediated growth and prevention of apoptosis: identification of an Achilles heel in leukemia. Leukemia 17:1058-1067.
3. Chan SM, Weng AP, Tibshirani R, Aster JC, and Utz PJ (2007) Notch signals positively regulate activity of the mTOR pathway in T-cell acute lymphoblastic leukemia. Blood 110:278-286.
4. D'Arpa P, Beardmore C, and Liu LF (1990) Involvement of nucleic acid synthesis in cell killing mechanisms of topoisomerase poisons. Cancer Res 50:6919-6924.
5. DeVries-Seimon TA, Ohm AM, Humphries MJ, and Reyland ME (2007) Induction of apoptosis is driven by nuclear retention of protein kinase C δ. J Biol Chem 282:22307-22314.
6. Eagar TN, Tang Q, Wolfe M, He Y, Pear WS, and Bluestone JA (2004) Notch 1 signaling regulates peripheral T cell activation. Immunity 20:407-415.
7. Fan QW, Knight ZA, Goldenberg DD, Yu W, Mostov KE, Stokoe D, Shokat KM, and Weiss WA (2006) A dual PI3 kinase/mTOR inhibitor reveals emergent efficacy in glioma. Cancer Cell 9:341-349.
8. Frame S and Cohen P (2001) GSK3 takes centre stage more than 20 years after its discovery. Biochem J 359:1-16.
9. Grabher C, von Boehmer H, and Look AT (2006) Notch 1 activation in the molecular pathogenesis of T-cell acute lymphoblastic leukaemia. Nat Rev Cancer 6:347-359.
10. Han EK, Leverson JD, McGonigal T, Shah OJ, Woods KW, Hunter T, Giranda VL, and Luo Y (2007) Akt inhibitor A-443654 induces rapid Akt Ser-473 phosphorylation independent of mTORC1 inhibition. Oncogene 26:5655-5661.
11. Katayama K, Fujita N, and Tsuruo T (2005) Akt/protein kinase B-dependent phosphorylation and inactivation of WEE1Hu promote cell cycle progression at G2/M transition. Mol Cell Biol 25:5725-5737.
12. Kazemi S, Mounir Z, Baltzis D, Raven JF, Wang S, Krishnamoorthy JL, Pluquet O, Pelletier J, and Koromilas AE (2007) A novel function of eIF2α kinases as inducers of the phosphoinositide-3 kinase signaling pathway. Mol Biol Cell 18:3635-3644.
13. Lindsley CW, Barnett SF, Layton ME, and Bilodeau MT (2008) The PI3K/Akt pathway: recent progress in the development of ATP-competitive and allosteric Akt kinase inhibitors. Curr Cancer Drug Targets 8:7-18.
14. Lopiccolo J, Blumenthal GM, Bernstein WB, and Dennis PA (2008) Targeting the PI3K/Akt/mTOR pathway: Effective combinations and clinical considerations. Drug Resist Updat 11:32-50.
15. Luo Y, Shoemaker AR, Liu X, Woods KW, Thomas SA, de Jong R, Han EK, Li T, Stoll VS, Powlas JA, et al. (2005) Potent and selective inhibitors of Akt kinases slow the progress of tumors in vivo. Mol Cancer Ther 4:977-986.
16. Mantovani I, Cappellini A, Tazzari PL, Papa V, Cocco L, and Martelli AM (2006) Caspase-dependent cleavage of 170-kDa P-glycoprotein during apoptosis of human T-lymphoblastoid CEM cells. J Cell Physiol 207:836-844.
17. Markovits J, Pommier Y, Kerrigan D, Covey JM, Tilchen EJ, and Kohn KW (1987) Topoisomerase II-mediated DNA breaks and cytotoxicity in relation to cell proliferation and the cell cycle in NIH 3T3 fibroblasts and L1210 leukemia cells. Cancer Res 47:2050-2055.
18. Marone R, Cmiljanovic V, Giese B, and Wymann MP (2008) Targeting phosphoinositide 3-kinase-Moving towards therapy. Biochim Biophys Acta 1784:159-185.
19. Martelli AM, Nyakern M, Tabellini G, Bortul R, Tazzari PL, Evangelisti C, and Cocco L (2006) Phosphoinositide 3-kinase/Akt signaling pathway and its therapeutical implications for human acute myeloid leukemia. Leukemia 20:911-928.
20. Neri LM, Borgatti P, Tazzari PL, Bortul R, Cappellini A, Tabellini G, Bellacosa A, Capitani S, and Martelli AM (2003) The phosphoinositide 3-kinase/AKT1 pathway involvement in drug and all-trans-retinoic acid resistance of leukemia cells. Mol Cancer Res 1:234-246.
21. Nyakern M, Cappellini A, Mantovani I, and Martelli AM (2006) Synergistic induction of apoptosis in human leukemia T cells by the Akt inhibitor perifosine and etoposide through activation of intrinsic and Fas-mediated extrinsic cell death pathways. Mol Cancer Ther 5:1559-1570.
22. Okumura E, Fukuhara T, Yoshida H, Hanada Si S, Kozutsumi R, Mori M, Tachibana K, and Kishimoto T (2002) Akt inhibits Myt1 in the signalling pathway that leads to meiotic G2/M-phase transition. Nat Cell Biol 4:111-116.
23. Palomero T, Sulis ML, Cortina M, Real PJ, Barnes K, Ciofani M, Caparros E, Buteau J, Brown K, Perkins SL, et al. (2007) Mutational loss of PTEN induces resistance to NOTCH1 inhibition in T-cell leukemia. Nat Med 13:1203-1210.
24. Papa V, Tazzari PL, Chiarini F, Cappellini A, Ricci F, Billi AM, Evangelisti C, Ottaviani E, Martinelli G, Testoni N, et al. (2008) Proapoptotic activity and chemosensitizing effect of the novel Akt inhibitor perifosine in acute myelogenous leukemia cells. Leukemia 22:147-160.
25. Sale EM and Sale GJ (2008) Protein kinase B: signalling roles and therapeutic targeting. Cell Mol Life Sci 65:113-127.
26. Seminario MC, Precht P, Wersto RP, Gorospe M, and Wange RL (2003) PTEN expression in PTEN-null leukaemic T cell lines leads to reduced proliferation via slowed cell cycle progression. Oncogene 22:8195-8204.
27. Shelton JG, Blalock WL, White ER, Steelman LS, and McCubrey JA (2004) Ability of the activated PI3K/Akt oncoproteins to synergize with MEK1 and induce cell cycle progression and abrogate the cytokine-dependence of hematopoietic cells. Cell Cycle 3:503-512.
28. Tafuri A, Gregorj C, Petrucci MT, Ricciardi MR, Mancini M, Cimino G, Mecucci C, Tedeschi A, Fioritoni G, Ferrara F, et al. (2002) MDR1 protein expression is an independent predictor of complete remission in newly diagnosed adult acute lymphoblastic leukemia. Blood 100:974-981.
29. Tazzari PL, Cappellini A, Ricci F, Evangelisti C, Papa V, Grafone T, Martinelli G, Conte R, Cocco L, McCubrey JA, et al. (2007a) Multidrug resistance-associated protein 1 expression is under the control of the phosphoinositide 3 kinase/Akt signal transduction network in human acute myelogenous leukemia blasts. Leukemia 21:427-438.
30. Tazzari PL, Tabellini G, Bortul R, Papa V, Evangelisti C, Grafone T, Martinelli G, McCubrey JA, and Martelli AM (2007b) The insulin-like growth factor-I receptor kinase inhibitor NVP-AEW541 induces apoptosis in acute myeloid leukemia cells exhibiting autocrine insulin-like growth factor-I secretion. Leukemia 21:886-896.
31. Tinel A and Tschopp J (2004) The PIDDosome, a protein complex implicated in activation of caspase-2 in response to genotoxic stress. Science 304:843-846.
32. Tokunaga E, Oki E, Egashira A, Sadanaga N, Morita M, Kakeji Y, and Maehara Y (2008) Deregulation of the Akt pathway in human cancer. Curr Cancer Drug Targets 8:27-36.
33. Uddin S, Hussain A, Al-Hussein K, Platanias LC, and Bhatia KG (2004) Inhibition of phosphatidylinositol 3′-kinase induces preferentially killing of PTEN-null T leukemias through AKT pathway. Biochem Biophys Res Commun 320:932-938.
34. Vitale A, Guarini A, Ariola C, Mancini M, Mecucci C, Cuneo A, Pane F, Saglio G, Cimino G, Tafuri A, et al. (2006a) Adult T-cell acute lymphoblastic leukemia: biologic profile at presentation and correlation with response to induction treatment in patients enrolled in the GIMEMA LAL 0496 protocol. Blood 107:473-479.
35. Vitale A, Guarini A, Chiaretti S, and Foa R (2006b) The changing scene of adult acute lymphoblastic leukemia. Curr Opin Oncol 18:652-659.
36. Weerkamp F, van Dongen JJ, and Staal FJ (2006) Notch and Wnt signaling in T-lymphocyte development and acute lymphoblastic leukemia. Leukemia 20:1197-1205.
37. Zhivotovsky B and Orrenius S (2005) Caspase-2 function in response to DNA damage. Biochem Biophys Res Commun 331:859-867.