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Dual inactivation of Akt and ERK by TIC10 signals Foxo3a nuclear translocation, TRAIL gene induction, and potent antitumor effects.

Allen JE, Krigsfeld G, Mayes PA, Patel L, Dicker DT, Patel AS, Dolloff NG, Messaris E, Scata KA, Wang W, Zhou JY, Wu GS, El-Deiry WS.

Sci Transl Med. 2013 Feb 6;5(171):171ra17. doi: 10.1126/scitranslmed.3004828.


Small-Molecule ONC201/TIC10 Targets Chemotherapy-Resistant Colorectal Cancer Stem-like Cells in an Akt/Foxo3a/TRAIL-Dependent Manner.

Prabhu VV, Allen JE, Dicker DT, El-Deiry WS.

Cancer Res. 2015 Apr 1;75(7):1423-32. doi: 10.1158/0008-5472.CAN-13-3451. Epub 2015 Feb 20.


Identification of TRAIL-inducing compounds highlights small molecule ONC201/TIC10 as a unique anti-cancer agent that activates the TRAIL pathway.

Allen JE, Krigsfeld G, Patel L, Mayes PA, Dicker DT, Wu GS, El-Deiry WS.

Mol Cancer. 2015 May 1;14:99. doi: 10.1186/s12943-015-0346-9.


The preclinical evaluation of TIC10/ONC201 as an anti-pancreatic cancer agent.

Zhang Q, Wang H, Ran L, Zhang Z, Jiang R.

Biochem Biophys Res Commun. 2016 Aug 5;476(4):260-266. doi: 10.1016/j.bbrc.2016.05.106. Epub 2016 May 24.


Purified vitexin compound 1 induces apoptosis through activation of FOXO3a in hepatocellular carcinoma.

Wang JG, Zheng XX, Zeng GY, Zhou YJ, Yuan H.

Oncol Rep. 2014 Jan;31(1):488-96. doi: 10.3892/or.2013.2855. Epub 2013 Nov 15.


Forkhead Box Transcription Factor (FOXO3a) mediates the cytotoxic effect of vernodalin in vitro and inhibits the breast tumor growth in vivo.

Ananda Sadagopan SK, Mohebali N, Looi CY, Hasanpourghadi M, Pandurangan AK, Arya A, Karimian H, Mustafa MR.

J Exp Clin Cancer Res. 2015 Dec 8;34:147. doi: 10.1186/s13046-015-0266-y.


Butein sensitizes human hepatoma cells to TRAIL-induced apoptosis via extracellular signal-regulated kinase/Sp1-dependent DR5 upregulation and NF-kappaB inactivation.

Moon DO, Kim MO, Choi YH, Kim GY.

Mol Cancer Ther. 2010 Jun;9(6):1583-95. doi: 10.1158/1535-7163.MCT-09-0942. Epub 2010 Jun 1.


IκB kinase overcomes PI3K/Akt and ERK/MAPK to control FOXO3a activity in acute myeloid leukemia.

Chapuis N, Park S, Leotoing L, Tamburini J, Verdier F, Bardet V, Green AS, Willems L, Agou F, Ifrah N, Dreyfus F, Bismuth G, Baud V, Lacombe C, Mayeux P, Bouscary D.

Blood. 2010 Nov 18;116(20):4240-50. doi: 10.1182/blood-2009-12-260711. Epub 2010 Jul 29.


Fluid shear stress suppresses TNF-α-induced apoptosis in MC3T3-E1 cells: Involvement of ERK5-AKT-FoxO3a-Bim/FasL signaling pathways.

Bin G, Bo Z, Jing W, Jin J, Xiaoyi T, Cong C, Liping A, Jinglin M, Cuifang W, Yonggang C, Yayi X.

Exp Cell Res. 2016 May 1;343(2):208-217. doi: 10.1016/j.yexcr.2016.03.014. Epub 2016 Apr 6.


TRAIL is involved in CpG ODN-mediated anti-apoptotic signals.

Lim EJ, Park DW, Jeong TW, Chin BR, Bae YS, Baek SH.

Oncol Rep. 2012 Apr;27(4):1213-8. doi: 10.3892/or.2011.1579. Epub 2011 Dec 6.


FOXO3A as a key molecule for all-trans retinoic acid-induced granulocytic differentiation and apoptosis in acute promyelocytic leukemia.

Sakoe Y, Sakoe K, Kirito K, Ozawa K, Komatsu N.

Blood. 2010 May 6;115(18):3787-95. doi: 10.1182/blood-2009-05-222976. Epub 2010 Mar 9.


T63, a new 4-arylidene curcumin analogue, induces cell cycle arrest and apoptosis through activation of the reactive oxygen species-FOXO3a pathway in lung cancer cells.

Liu H, Zhou BH, Qiu X, Wang HS, Zhang F, Fang R, Wang XF, Cai SH, Du J, Bu XZ.

Free Radic Biol Med. 2012 Dec 15;53(12):2204-17. doi: 10.1016/j.freeradbiomed.2012.10.537. Epub 2012 Oct 17.


Abelson virus transformation prevents TRAIL expression by inhibiting FoxO3a and NF-kappaB.

Wilson MK, McWhirter SM, Amin RH, Huang D, Schlissel MS.

Mol Cells. 2010 Apr;29(4):333-41. doi: 10.1007/s10059-010-0029-8. Epub 2010 Mar 4.


ONC201 induces cell death in pediatric non-Hodgkin's lymphoma cells.

Talekar MK, Allen JE, Dicker DT, El-Deiry WS.

Cell Cycle. 2015 Aug 3;14(15):2422-8. doi: 10.1080/15384101.2015.1054086. Epub 2015 Jun 1.


Pharmacophore reassignment for induction of the immunosurveillance cytokine TRAIL.

Jacob NT, Lockner JW, Kravchenko VV, Janda KD.

Angew Chem Int Ed Engl. 2014 Jun 23;53(26):6628-31. doi: 10.1002/anie.201402133. Epub 2014 May 18.


The alkylphospholipid perifosine induces apoptosis of human lung cancer cells requiring inhibition of Akt and activation of the extrinsic apoptotic pathway.

Elrod HA, Lin YD, Yue P, Wang X, Lonial S, Khuri FR, Sun SY.

Mol Cancer Ther. 2007 Jul;6(7):2029-38. Epub 2007 Jun 29.


TG-interacting factor transcriptionally induced by AKT/FOXO3A is a negative regulator that antagonizes arsenic trioxide-induced cancer cell apoptosis.

Liu ZM, Tseng HY, Cheng YL, Yeh BW, Wu WJ, Huang HS.

Toxicol Appl Pharmacol. 2015 May 15;285(1):41-50. doi: 10.1016/j.taap.2015.03.007. Epub 2015 Mar 16.


Constitutive and ligand-induced EGFR signalling triggers distinct and mutually exclusive downstream signalling networks.

Chakraborty S, Li L, Puliyappadamba VT, Guo G, Hatanpaa KJ, Mickey B, Souza RF, Vo P, Herz J, Chen MR, Boothman DA, Pandita TK, Wang DH, Sen GC, Habib AA.

Nat Commun. 2014 Dec 15;5:5811. doi: 10.1038/ncomms6811.

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