The Akt inhibitor MK-2206 enhances the cytotoxicity of paclitaxel (Taxol) and cisplatin in ovarian cancer cells

Naunyn-Schmiedeberg's Archives of Pharmacology

Volumn 388, Issue 1, 2014, Pages 19-31

  Lin, Ying Hsi ^a   Chen, Bert Yu Hung ^a   Lai, Wei Ting ^a   Wu, Shao Fu ^a   Guh, Jih Hwa ^a   Cheng, Ann Lii ^b   Hsu, Lih Ching ^a  

^a NATIONAL TAIWAN UNIVERSITY   (Taiwan)

^b NATIONAL TAIWAN UNIVERSITY HOSPITAL   (Taiwan)

Author keywords

Akt inhibitor MK 2206; Cisplatin; Ovarian cancer; Paclitaxel (Taxol); PI3K Akt signaling pathway

Indexed keywords

8 [4 (1 AMINOCYCLOBUTYL)PHENYL] 9 PHENYL 1,2,4 TRIAZOLO[3,4 F][1,6]NAPHTHYRIDIN 3(2H) ONE; CISPLATIN; PACLITAXEL; PROTEIN BCL 2; PROTEIN KINASE B; PROTEIN P53; REACTIVE OXYGEN METABOLITE; ANTINEOPLASTIC AGENT; FUSED HETEROCYCLIC RINGS; PROTEIN KINASE INHIBITOR;

ARTICLE; CELL DEATH; CELL PROLIFERATION; DNA REPAIR; DOWN REGULATION; DRUG CYTOTOXICITY; DRUG EFFICACY; DRUG MECHANISM; DRUG POTENTIATION; FEMALE; GROWTH INHIBITION; HUMAN; HUMAN CELL; OVARIAN CANCER CELL LINE; OVARY CANCER; PROTEIN PHOSPHORYLATION; ANTAGONISTS AND INHIBITORS; CELL SURVIVAL; DRUG EFFECTS; METABOLISM; OVARIAN NEOPLASMS; TUMOR CELL LINE;

ANTINEOPLASTIC AGENTS; CELL LINE, TUMOR; CELL PROLIFERATION; CELL SURVIVAL; CISPLATIN; DRUG SYNERGISM; FEMALE; HETEROCYCLIC COMPOUNDS, 3-RING; HUMANS; OVARIAN NEOPLASMS; PACLITAXEL; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS C-AKT; PROTO-ONCOGENE PROTEINS C-BCL-2; REACTIVE OXYGEN SPECIES; TUMOR SUPPRESSOR PROTEIN P53;

EID: 84920389282     PISSN: 00281298     EISSN: 14321912     Source Type: Journal    
DOI: 10.1007/s00210-014-1032-y     Document Type: Article

References (26)

1. Agarwal R, Kaye SB (2003) Ovarian cancer: strategies for overcoming resistance to chemotherapy. Nat Rev Cancer 3:502-516. doi: 10.1038/nrc1123
2. Alessi DR, Andjelkovic M, Caudwell B, Cron P, Morrice N, Cohen P, Hemmings BA (1996) Mechanism of activation of protein kinase B by insulin and IGF-1. EMBO J 15:6541-6551
3. Berkenblit A, Cannistra SA (2005) Advances in the management of epithelial ovarian cancer. J Reprod Med 50:426-438
4. Caro AA, Cederbaum AI (2006) Role of phosphatidylinositol 3-kinase/AKT as a survival pathway against CYP2E1-dependent toxicity. J Pharmacol Exp Ther 318:360-372. doi: 10.1124/jpet.106.102921
5. Chen H, Ma Z, Vanderwaal RP, Feng Z, Gonzalez-Suarez I, Wang S, Zhang J, Roti Roti JL, Gonzalo S, Zhang J (2011) The mTOR inhibitor rapamycin suppresses DNA double-strand break repair. Radiat Res 175:214-224
6. Cheng Y, Ren X, Zhang Y, Patel R, Sharma A, Wu H, Robertson GP, Yan L, Rubin E, Yang JM (2011) eEF-2 kinase dictates crosstalk between autophagy and apoptosis induced by Akt inhibition, thereby modulating cytotoxicity of novel Akt inhibitor MK-2206. Cancer Res 71:2654-2663. doi: 10.1158/0008-5472.CAN-10-2889
7. Chou TC, Talalay P (1984) Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzym Regul 22:27-55
8. Concin N, Stimpfl M, Zeillinger C, Wolff U, Hefler LJ, Sedlak J, Leodolter S, Zeillinger R (2003) Role of p53 in G2/M cell cycle arrest and apoptosis in response to gamma-irradiation in ovarian carcinoma cell lines. Int J Oncol 22:51-57
9. Courtney KD, Corcoran RB, Engelman JA (2010) The PI3K pathway as drug target in human cancer. J Clin Oncol 28:1075-1083. doi: 10.1200/JCO.2009.25.3641
10. DiSaia PJ, Bloss JD (2003) Treatment of ovarian cancer: new strategies. Gynecol Oncol 90:S24-32
11. El-Gazzar A, Perco P, Eckelhart E, Anees M, Sexl V, Mayer B, Liu Y, Mikulits W, Horvat R, Pangeri T, Zheng D, Krainer M (2010) Natural immunity enhances the activity of a DR5 agonistic antibody and carboplatin in the treatment of ovarian cancer. Mol Cancer Ther 9:1007-1018. doi: 10.1158/1535-7163.MCT-09-0933
12. Hanrahan AJ, Schultz N, Westfal ML, Sakr RA, Giri DD, Scarperi S, Janakiraman M, Olvera N, Stevens EV, She QB, Aghajanian C, King TA, Stanchina E, Spriggs DR, Heguy A, Taylor BS, Sander C, Rosen N, Levine DA, Solit DB (2012) Genomic complexity and AKT dependence in serous ovarian cancer. Cancer Discov 2:56-67
13. Hirai H, Sootome H, Nakatsuru Y, Miyama K, Taguchi S, Tsujioka K, Ueno Y, Hatch H, Majumder PK, Pan BS, Kotani H (2010) MK-2206, an allosteric Akt inhibitor, enhances antitumor efficacy by standard chemotherapeutic agents or molecular targeted drugs in vitro and in vivo. Mol Cancer Ther 9:1956-1967. doi: 10.1158/1535-7163.MCT-09-1012
14. Hsu LC, Kapali M, DeLoia JA, Gallion HH (2005) Centrosome abnormalities in ovarian cancer. Int J Cancer 113:746-751
15. Li Z, Yan S, Attayan N, Ramalingam S, Thiele CJ (2012) Combination of an allosteric Akt inhibitor MK-2206 with etoposide or rapamycin enhances the antitumor growth effect in neuroblastoma. Clin Cancer Res 18:3603-3615. doi: 10.1158/1078-0432.CCR-11-3321
16. Lindsley CW, Barnett SF, Layton ME, 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
17. Liu P, Cheng T, Roberts TM, Zhao JJ (2009) Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov 8:627-644. doi: 10.1038/nrd2926
18. Mendoza MC, Er EE, Blenis J (2011) The Ras-ERK and PI3K-mTOR pathways: cross-talk and compensation. Trends Biochem Sci 36:320-328
19. Paull TT, Rogakou EP, Yamazaki V, Kirchgessner CU, Gellert M, Bonner WM (2000) A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage. Curr Biol 10:886-895
20. Peng DJ, Wang J, Zhou JY, Wu GS (2010) Role of the Akt/mTOR survival pathway in cisplatin resistance in ovarian cancer cells. Biochem Biophys Res Commun 394:600-605. doi: 10.1016/j.bbrc.2010.03.029
21. Scully R, Chen J, Ochs RL, Keegan K, Hoekstra M, Feunteun J, Livingston DM (1997) Dynamic changes of BRCA1 subnuclear location and phosphorylation state are initiated by DNA damage. Cell 90:425-435
22. Sun M, Wang G, Paciga JE, Feldman RI, Yuan ZQ, Ma XL, Shelley SA, Jove R, Tsichlis PN, Nicosia SV, Cheng JQ (2001) AKT1/PKBalpha kinase is frequently elevated in human cancers and its constitutive activation is required for oncogenic transformation in NIH3T3 cells. Am J Pathol 159:431-437
23. West KA, Castillo SS, Dennis PA (2002) Activation of the PI3K/Akt pathway and chemotherapeutic resistance. Drug Resist Updat 5:234-248
24. Yu YM, Pace SM, Allen SR, Deng CX, Hsu LC (2008) A PP1-binding motif present in BRCA1 plays a role in its DNA repair function. Int J Biol Sci 4:352-361. doi: 10.7150/ijbs.4.352
25. Yuan ZQ, Sun M, Feldman RI (2000) Frequent activation of AKT2 and induction of apoptosis by inhibition of phosphoinositide-3-OH kinase/Akt pathway in human ovarian cancer. Oncogene 19:2324-2330. doi: 10.1038/sj.onc.1203598
26. Zhao L, Wientjes MG, Au JL (2004) Evaluation of combination chemotherapy: integration of nonlinear regression, curve shift, isobologram, and combination index analyses. Clin Cancer Res 10:7994-8004. doi: 10.1158/1078-0432.CCR-04-1087