Blood 2006, 107:2501–2506.PubMedCrossRef 18. Orsolic N, Golemovic M, Quintas-Cardama A, Scappini B, Manshouri T, Chandra J, Basic I, Giles F, Kantarjian H, Verstovsek S: Adaphostin has significant and selective activity against chronic and acute myeloid leukemia cells. Cancer Sci 2006, 97:952–960.PubMedCrossRef 19. Yu C, Rahmani M, Almenara J, Sausville EA, Dent P, Grant S: Induction of apoptosis in human leukemia cells by the tyrosine kinase inhibitor adaphostin proceeds through a RAF-1/MEK/ERK- and AKT-dependent process. Oncogene 2004, 23:1364–1376.PubMedCrossRef 20. Lee JM, Hanson

JM, Chu WA, Johnson JA: Phosphatidylinositol 3-kinase, not extracellular signal-regulated kinase, regulates activation

of the antioxidant-responsive element LY3023414 in vivo in IMR-32 human BI 2536 chemical structure neuroblastoma cells. J Biol Chem 2001, 276:20011–20016.PubMedCrossRef 21. Kang KW, Lee SJ, Park JW, Kim SG: Phosphatidylinositol 3-kinase regulates nuclear translocation of NF-E2-related factor 2 through actin rearrangement in response to oxidative stress. Mol Pharmacol 2002, 62:1001–1010.PubMedCrossRef 22. Dasmahapatra G, Nguyen TK, Dent P, Grant S: Adaphostin and bortezomib induce oxidative injury and apoptosis in imatinib mesylate-resistant hematopoietic cells expressing mutant forms of Bcr/Abl. Leuk Res 2006, 30:1263–1272.PubMedCrossRef 23. Le SB, Hailer MK, Buhrow S, Wang Q, Flatten K, Pediaditakis P, Bible KC, Lewis LD, Sausville EA, Pang YP, Ames MM, Lemasters JJ, Holmuhamedov EL, Kaufman SH: Torin 1 mouse Inhibition of mitochondrial respiration as a source of adaphostin-induced reactive oxygen species and cytotoxicity. J Biol Chem 2007, 282:8860–8872.PubMedCrossRef 24. Shanafelt fantofarone TD, Lee YK, Bone ND, Strege AK, Narayanan VL, Sausville EA, Geyer SM,

Kaufmann SH, Kay NE: Adaphostin-induced apoptosis in CLL B cells is associated with induction of oxidative stress and exhibits synergy with fludarabine. Blood 2005, 105:2099–2106.PubMedCrossRef 25. Stockwin LH, Bumke MA, Yu SX, Webb SP, Collins JR, Hollingshead MG, Newton DL: Proteomic analysis identifies oxidative stress induction by adaphostin. Clin Cancer Res 2007, 13:3667–3681.PubMedCrossRef 26. Surh YJ, Kundu JK, Na HK: Nrf2 as a master redox switch in turning on the cellular signaling involved in the induction of cytoprotective genes by some chemopreventive phytochemicals. Planta Med 2008, 74:1526–1539.PubMedCrossRef 27. Li W, Khor TO, Xu C, Shen G, Jeong WS, Yu S, Kong AN: Activation of Nrf2-antioxidant signaling attenuates NFkappaB-inflammatory response and elicits apoptosis. Biochem Pharmacol 2008, 76:1485–1489.PubMedCrossRef 28. Akhdar H, Loyer P, Rauch C, Corlu A, Guillouzo A, Morel F: Involvement of Nrf2 activation in resistance to 5-fluorouracil in human colon cancer HT-29 cells. Eur J Cancer 2009, 45:2219–2227.PubMedCrossRef 29.