Combining AKT inhibition with chloroquine and gefitinib prevents compensatory autophagy and induces cell death in EGFR mutated NSCLC cells

Oncotarget

Volumn 5, Issue 13, 2014, Pages 4765-4778

  Bokobza, Sivan M ^a   Jiang, Yanyan ^a   Weber, Anika M ^a   Devery, Aoife M ^a   Ryan, Anderson J ^a  

^a UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

AKT; Chloroquine; EGFR; Lung cancer

Indexed keywords

8 [4 (1 AMINOCYCLOBUTYL)PHENYL] 9 PHENYL 1,2,4 TRIAZOLO[3,4 F][1,6]NAPHTHYRIDIN 3(2H) ONE; CHLOROQUINE; EPIDERMAL GROWTH FACTOR RECEPTOR; GEFITINIB; PROTEIN KINASE B; PROTEIN KINASE B BETA; SMALL INTERFERING RNA; AKT2 PROTEIN, HUMAN; ANTINEOPLASTIC AGENT; FUSED HETEROCYCLIC RINGS; QUINAZOLINE DERIVATIVE;

ANIMAL EXPERIMENT; ANIMAL MODEL; APOPTOSIS; ARTICLE; AUTOPHAGY; CANCER INHIBITION; CONTROLLED STUDY; DRUG POTENTIATION; DRUG SENSITIVITY; FEMALE; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; LUNG CANCER CELL LINE; LUNG NON SMALL CELL CANCER; MOUSE; NONHUMAN; SIGNAL TRANSDUCTION; TUMOR REGRESSION; TUMOR XENOGRAFT; ANIMAL; ANTAGONISTS AND INHIBITORS; BAGG ALBINO MOUSE; CARCINOMA, NON-SMALL-CELL LUNG; CELL PROLIFERATION; CELL SURVIVAL; DRUG EFFECTS; DRUG SCREENING; GENETICS; LUNG NEOPLASMS; METABOLISM; MUTATION; NUDE MOUSE; RNA INTERFERENCE; TUMOR CELL LINE; WESTERN BLOTTING;

ANIMALS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; APOPTOSIS; AUTOPHAGY; BLOTTING, WESTERN; CARCINOMA, NON-SMALL-CELL LUNG; CELL LINE, TUMOR; CELL PROLIFERATION; CELL SURVIVAL; CHLOROQUINE; DRUG SYNERGISM; FEMALE; HETEROCYCLIC COMPOUNDS, 3-RING; HUMANS; LUNG NEOPLASMS; MICE, INBRED BALB C; MICE, NUDE; MUTATION; PROTO-ONCOGENE PROTEINS C-AKT; QUINAZOLINES; RECEPTOR, EPIDERMAL GROWTH FACTOR; RNA INTERFERENCE; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84905027834     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.2017     Document Type: Article

References (53)

1. Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D. Global Cancer Statistics. Ca-a Cancer Journal for Clinicians. 2011; 61(2):69-90.
2. Brambilla E, Travis WD, Colby TV, Corrin B and Shimosato Y. The new World Health Organization classification of lung tumours. European Respiratory Journal. 2001; 18(6):1059-1068.
3. Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, Harris PL, Haserlat SM, Supko JG, Haluska FG, Louis DN, Christiani DC, Settleman J and Haber DA. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. New England Journal of Medicine. 2004; 350(21):2129-2139.
4. Pao W, Miller V, Zakowski M, Doherty J, Politi K, Sarkaria I, Singh B, Heelan R, Rusch V, Fulton L, Mardis E, Kupfer D, Wilson R, Kris M and Varmus H. EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib. Proceedings of the National Academy of Sciences of the United States of America. 2004; 101(36):13306-13311.
5. Kobayashi S, Boggon TJ, Dayaram T, Janne PA, Kocher O, Meyerson M, Johnson BE, Eck MJ, Tenen DG and Halmos B. EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. New England Journal of Medicine. 2005; 352(8):786-792.
6. Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, Sunpaweravong P, Han BH, Margono B, Ichinose Y, Nishiwaki Y, Ohe Y, Yang JJ, Chewaskulyong B, Jiang HY, Duffield EL, et al. Gefitinib or Carboplatin-Paclitaxel in Pulmonary Adenocarcinoma. New Engl J Med. 2009; 361(10):947-957.
7. Holbro T and Hynes NE. ErbB receptors: Directing key signaling networks throughout life. Annual Review of Pharmacology and Toxicology. 2004; 44:195-217.
8. Manning BD and Cantley LC. AKT/PKB signaling: Navigating downstream. Cell. 2007; 129(7):1261-1274.
9. Brazil DP, Yang ZZ and Hemmings BA. Advances in protein kinase B signalling: AKTion on multiple fronts. Trends in Biochemical Sciences. 2004; 29(5):233-242.
10. Irie HY, Pearline RV, Grueneberg D, Hsia M, Ravichandran P, Kothari N, Natesan S and Brugge JS. Distinct roles of Akt1 and Akt2 in regulating cell migration and epithelial-mesenchymal transition. Journal of Cell Biology. 2005; 171(6):1023-1034.
11. Meng Q, Xia C, Fang J, Rojanasakul Y and Jiang BH. Role of PI3K and AKT specific isoforms in ovarian cancer cell migration, invasion and proliferation through the p70S6K1 pathway. Cellular Signalling. 2006; 18(12):2262-2271.
12. Hollander MC, Maier CR, Hobbs EA, Ashmore AR, Linnoila RI and Dennis PA. Akt1 deletion prevents lung tumorigenesis by mutant K-ras. Oncogene. 2011; 30(15):1812-1821.
13. Lee MW, Kim DS, Lee JH, Lee BS, Lee SH, Jung HL, Sung KW, Kim HT, Yoo KH and Koo HH. Roles of AKT1 and AKT2 in non-small cell lung cancer cell survival, growth, and migration. Cancer Science. 2011; 102(10):1822-1828.
14. Arboleda MJ, Lyons JF, Kabbinavar FF, Bray MR, Snow BE, Ayala R, Danino M, Karlan BY and Slamon DJ. Overexpression of AKT2/protein kinase B beta leads to up-regulation of beta 1 integrins, increased invasion, and metastasis of human breast and ovarian cancer cells. Cancer research. 2003; 63(1):196-206.
15. Tolcher AW, Yap TA, Fearen I, Taylor A, Carpenter C, Brunetto AT, Beeram M, Papadopoulos K, Yan L and de Bono J. A phase I study of MK-2206, an oral potent allosteric Akt inhibitor (Akti), in patients (pts) with advanced solid tumor (ST). Journal of Clinical Oncology. 2009; 27(15).
16. Yap TA, Yan L, Patnaik A, Fearen I, Olmos D, Papadopoulos K, Baird RD, Delgado L, Taylor A, Lupinacci L, Riisnaes R, Pope LL, Heaton SP, Thomas G, Garrett MD, Sullivan DM, et al. First-in-Man Clinical Trial of the Oral Pan-AKT Inhibitor MK-2206 in Patients With Advanced Solid Tumors. Journal of Clinical Oncology. 2011; 29(35):4688-4695.
17. Lamoureux F, Thomas C, Crafter C, Kumano M, Zhang F, Davies BR, Gleave ME and Zoubeidi A. Blocked autophagy using lysosomotropic agents sensitizes resistant prostate tumor cells to the novel Akt inhibitor AZD5363. Clinical cancer research: an official journal of the American Association for Cancer Research. 2013; 19(4):833-844.
18. Santi SA and Lee H. Ablation of Akt2 induces autophagy through cell cycle arrest, the downregulation of p70S6K, and the deregulation of mitochondria in MDA-MB231 cells. Plos One. 2011; 6(1):e14614.
19. Hung JY, Hsu YL, Li CT, Ko YC, Ni WC, Huang MS and Kuo PL. 6-Shogaol, an active constituent of dietary ginger, induces autophagy by inhibiting the AKT/mTOR pathway in human non-small cell lung cancer A549 cells. Journal of agricultural and food chemistry. 2009; 57(20):9809-9816.
20. Noda T, Fujita N and Yoshimori T. The late stages of autophagy: how does the end begin? Cell death and differentiation. 2009; 16(7):984-990.
21. Mathew R, Kongara S, Beaudoin B, Karp CM, Bray K, Degenhardt K, Chen G, Jin S and White E. Autophagy suppresses tumor progression by limiting chromosomal instability. Genes & development. 2007; 21(11):1367-1381.
22. Ogier-Denis E and Codogno P. Autophagy: a barrier or an adaptive response to cancer. Biochimica et biophysica acta. 2003; 1603(2):113-128.
23. Mancias JD and Kimmelman AC. Targeting autophagy addiction in cancer. Oncotarget. 2011; 2(12):1302-1306.
24. Wu Z, Chang PC, Yang JC, Chu CY, Wang LY, Chen NT, Ma AH, Desai SJ, Lo SH, Evans CP, Lam KS and Kung HJ. Autophagy Blockade Sensitizes Prostate Cancer Cells towards Src Family Kinase Inhibitors. Genes & cancer. 2010; 1(1):40-49.
25. Chou TC and Talalay P. Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul. 1984; 22:27-55.
26. Barnett SF, Defeo-Jones D, Fu S, Hancock PJ, Haskell KM, Jones RE, Kahana JA, Kral AM, Leander K, Lee LL, Malinowski J, McAvoy EM, Nahas DD, Robinson RG and Huber HE. Identification and characterization of pleckstrin-homology-domain-dependent and isoenzyme-specific Akt inhibitors. The Biochemical journal. 2005; 385(Pt 2):399-408.
27. Zhao Z, Robinson RG, Barnett SF, Defeo-Jones D, Jones RE, Hartman GD, Huber HE, Duggan ME and Lindsley CW. Development of potent, allosteric dual Akt1 and Akt2 inhibitors with improved physical properties and cell activity. Bioorganic & medicinal chemistry letters. 2008; 18(1):49-53.
28. Kabeya Y, Mizushima N, Ueno T, Yamamoto A, Kirisako T, Noda T, Kominami E, Ohsumi Y and Yoshimori T. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. The EMBO journal. 2000; 19(21):5720-5728.
29. Maclean KH, Dorsey FC, Cleveland JL and Kastan MB. Targeting lysosomal degradation induces p53-dependent cell death and prevents cancer in mouse models of lymphomagenesis. The Journal of clinical investigation. 2008; 118(1):79-88.
30. Li H, Schmid-Bindert G, Wang D, Zhao Y, Yang X, Su B and Zhou C. Blocking the PI3K/AKT and MEK/ERK signaling pathways can overcome Gefitinib-resistance in non-small cell lung cancer cell lines. Adv Med Sci-Poland. 2011; 56(2):275-284.
31. Ananiev G, Williams EC, Li HD and Chang Q. Isogenic Pairs of Wild Type and Mutant Induced Pluripotent Stem Cell (iPSC) Lines from Rett Syndrome Patients as In Vitro Disease Model. Plos One. 2011; 6(9).
32. Wu K, Chang Q, Lu Y, Qiu P, Chen B, Thakur C, Sun J, Li L, Kowluru A and Chen F. Gefitinib resistance resulted from STAT3-mediated Akt activation in lung cancer cells. Oncotarget. 2013; 4(12):2430-2438.
33. Hirai H, Sootome H, Nakatsuru Y, Miyama K, Taguchi S, Tsujioka K, Ueno Y, Hatch H, Majumder PK, Pan BS and Kotani H. 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. 2010; 9(7):1956-1967.
34. Cheng Y, Zhang Y, Zhang L, Ren XC, Huber-Keener KJ, Liu XY, Zhou L, Liao J, Keihack H, Yan L, Rubin E and Yang JM. MK-2206, a Novel Allosteric Inhibitor of Akt, Synergizes with Gefitinib against Malignant Glioma via Modulating Both Autophagy and Apoptosis. Mol Cancer Ther. 2012; 11(1):154-164.
35. Paez JG, Janne PA, Lee JC, Tracy S, Greulich H, Gabriel S, Herman P, Kaye FJ, Lindeman N, Boggon TJ, Naoki K, Sasaki H, Fujii Y, Eck MJ, Sellers WR, Johnson BE, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 2004; 304(5676):1497-1500.
36. Cheng Y, Zhang Y, Zhang L, Ren X, Huber-Keener KJ, Liu X, Zhou L, Liao J, Keihack H, Yan L, Rubin E and Yang JM. MK-2206, a novel allosteric inhibitor of Akt, synergizes with gefitinib against malignant glioma via modulating both autophagy and apoptosis. Mol Cancer Ther. 2012; 11(1):154-164.
37. Cherrin C, Haskell K, Howell B, Jones R, Leander K, Robinson R, Watkins A, Bilodeau M, Hoffman J, Sanderson P, Hartman G, Mahan E, Prueksaritanont T, Jiang G, She QB, Rosen N, et al. An allosteric Akt inhibitor effectively blocks Akt signaling and tumor growth with only transient effects on glucose and insulin levels in vivo. Cancer Biol Ther. 2010; 9(7):493-503.
38. Tolcher AW. Stable disease is a valid end point in clinical trials. Cancer J. 2009; 15(5):374-378.
39. Hollander MC, Zhou X, Maier CR, Patterson AD, Ding XX and Dennis PA. A Cyp2a polymorphism predicts susceptibility to NNK-induced lung tumorigenesis in mice. Carcinogenesis. 2011; 32(8):1279-1284.
40. Yoon YK, Kim HP, Han SW, Oh DY, Im SA, Bang YJ and Kim TY. KRAS Mutant Lung Cancer Cells Are Differentially Responsive to MEK Inhibitor Due to AKT or STAT3 Activation: Implication for Combinatorial Approach. Mol Carcinogen. 2010; 49(4):353-362.
41. Grabinski N, Bartkowiak K, Grupp K, Brandt B, Pantel K and Jucker M. Distinct functional roles of Akt isoforms for proliferation, survival, migration and EGF-mediated signalling in lung cancer derived disseminated tumor cells. Cellular Signalling. 2011; 23(12):1952-1960.
42. Kimura T, Takabatake Y, Takahashi A and Isaka Y. Chloroquine in cancer therapy: a double-edged sword of autophagy. Cancer research. 2013; 73(1):3-7.
43. CufiS, Vazquez-Martin A, Oliveras-Ferraros C, Corominas-Faja B, Urruticoechea A, Martin-Castillo B and Menendez JA. Autophagy-related gene 12 (ATG12) is a novel determinant of primary resistance to HER2-targeted therapies: utility of transcriptome analysis of the autophagy interactome to guide breast cancer treatment. Oncotarget. 2012; 3(12):1600-1614.
44. Li YY, Lam SK, Mak JC, Zheng CY and Ho JC. Erlotinib-induced autophagy in epidermal growth factor receptor mutated non-small cell lung cancer. Lung cancer. 2013; 81(3):354-361.
45. Wei Y, Zou Z, Becker N, Anderson M, Sumpter R, Xiao G, Kinch L, Koduru P, Christudass CS, Veltri RW, Grishin NV, Peyton M, Minna J, Bhagat G and Levine B. EGFR-mediated Beclin 1 phosphorylation in autophagy suppression, tumor progression, and tumor chemoresistance. Cell. 2013; 154(6):1269-1284.
46. Fan C, Wang W, Zhao B, Zhang S and Miao J. Chloroquine inhibits cell growth and induces cell death in A549 lung cancer cells. Bioorganic & medicinal chemistry. 2006; 14(9):3218-3222.
47. Schmukler E, Wolfson E, Haklai R, Elad-Sfadia G, Kloog Y and Pinkas-Kramarski R. Chloroquine synergizes with FTS to enhance cell growth inhibition and cell death. Oncotarget. 2014; 5(1):173-184.
48. Amaravadi RK, Lippincott-Schwartz J, Yin XM, Weiss WA, Takebe N, Timmer W, DiPaola RS, Lotze MT and White E. Principles and current strategies for targeting autophagy for cancer treatment. Clinical cancer research: an official journal of the American Association for Cancer Research. 2011; 17(4):654-666.
49. Blagosklonny MV. Matching targets for selective cancer therapy. Drug discovery today. 2003; 8(24):1104-1107.
50. Hutter G, Nickenig C, Garritsen H, Hellenkamp F, Hoerning A, Hiddemann W and Dreyling M. Use of polymorphisms in the noncoding region of the human mitochondrial genome to identify potential contamination of human leukemia-lymphoma cell lines. The hematology journal: the official journal of the European Haematology Association/EHA. 2004; 5(1):61-68.
51. Chou TC. Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies. Pharmacol Rev. 2006; 58(3):621-681.
52. Chou TC. Drug combination studies and their synergy quantification using the Chou-Talalay method. Cancer Res. 2010; 70(2):440-446.
53. Workman P, Aboagye EO, Balkwill F, Balmain A, Bruder G, Chaplin DJ, Double JA, Everitt J, Farningham DAH, Glennie MJ, Kelland LR, Robinson V, Stratford IJ, Tozer GM, Watson S, Wedge SR, et al. Guidelines for the welfare and use of animals in cancer research. Br J Cancer. 2010; 102(11):1555-1577.