Aerosolised 5-azacytidine suppresses tumour growth and reprogrammes the epigenome in an orthotopic lung cancer model

British Journal of Cancer

Volumn 109, Issue 7, 2013, Pages 1775-1781

  Reed, M D ^a   Tellez, C S ^a   Grimes, M J ^a   Picchi, M A ^a   Tessema, M ^a   Cheng, Y S ^a   March, T H ^a   Kuehl, P J ^a   Belinsky, S A ^a  

^a LOVELACE RESPIRATORY RESEARCH INSTITUTE   (United States)

Author keywords

5 azacytidine; aerosol delivery; epigenome; gene methylation; lung cancer

Indexed keywords

AZACITIDINE; PROTEIN; PROTEIN BAD; PROTEIN BAK; PROTEIN BIK; PROTEIN BOK; UNCLASSIFIED DRUG;

AEROSOL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CANCER INHIBITION; CONTROLLED STUDY; CPG ISLAND; DEMETHYLATION; DRUG DELIVERY SYSTEM; DRUG HALF LIFE; EPIGENETICS; LUNG CANCER; LUNG LOBE; LUNG PARENCHYMA; MALE; NONHUMAN; PHARMACOKINETICS; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN EXPRESSION; RAT; TREATMENT RESPONSE;

ADMINISTRATION, INHALATION; AEROSOLS; ANIMALS; ANTIMETABOLITES, ANTINEOPLASTIC; AZACITIDINE; BENZAMIDES; CYTIDINE DEAMINASE; DNA METHYLATION; EPIGENESIS, GENETIC; HISTONE DEACETYLASE INHIBITORS; LUNG NEOPLASMS; MALE; NEOPLASM TRANSPLANTATION; PYRIDINES; RATS; TUMOR BURDEN;

EID: 84885183510     PISSN: 00070920     EISSN: 15321827     Source Type: Journal    
DOI: 10.1038/bjc.2013.575     Document Type: Article

References (35)

1. Belinsky SA (2005) Silencing of genes by promoter hypermethylation: key event in rodent and human lung cancer. Carcinogenesis 26: 1481-1487.
2. Belinsky SA, Grimes MJ, Picchi MA, Mitchell HD, Stidley CA, Tesfaigzi Y, Channell MM, Liu Y, Casero Jr RA, Baylin SB, Reed MD, Tellez CS, March TH (2011) Combination therapy with vidaza and entinostat suppresses tumor growth and reprograms the epigenome in an orthotopic lung cancer model. Cancer Res 71: 454-462.
3. Belinsky SA, Klinge DM, Stidley CA, Issa JP, Herman JG, March TH, Baylin SB (2003) Inhibition of DNA methylation and histone deacetylation prevents murine lung cancer. Cancer Res 63: 7089-7093.
4. Belinsky SA, Liechty KC, Gentry FD, Wolf HJ, Rogers J, Vu K, Haney J, Kennedy TC, Hirsch FR, Miller Y, Franklin WA, Herman JG, Baylin SB, Bunn PA, Byers T (2006) Promoter hypermethylation of multiple genes in sputum precedes lung cancer incidence in a high-risk cohort. Cancer Res 66: 3338-3344.
5. Bide RW, Armour SJ, Yee E (2000) Allometric respiration/body mass data for animals to be used for estimates of inhalation toxicity to young adult humans. J Appl Toxicol 20: 273-290.
6. Brena RM, Morrison C, Liyanarachchi S, Jarjoura D, Davuluri RV, Otterson GA, Reisman D, Glaros S, Rush LJ, Plass C (2007) Aberrant DNA methylation of OLIG1, a novel prognostic factor in non-small cell lung cancer. PLoS Med 4: e108.
7. Cameron EE, Bachman KE, Myohanen S, Herman JG, Baylin SB (1999) Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer. Nat Genet 21: 103-107.
8. El-Gendy N, Berkland C (2009) Combination chemotherapeutic dry powder aerosols via controlled nanoparticle agglomeration. Pharm Res 26: 1752-1763.
9. Fang M, Chen D, Yang CS (2007) Dietary polyphenols may affect DNA methylation. J Nutr 137: 223S-228S.
10. Fitzgerald SM, Goyal RK, Osborne WR, Roy JD, Wilson JW, Ferrell RE (2006) Identification of functional single nucleotide polymorphism haplotypes in the cytidine deaminase promoter. Hum Genet 119: 276-283.
11. Gagnadoux F, Hureaux J, Vecellio L, Urban T, Le Pape A, Valo I, Montharu J, Leblond V, Boisdron-Celle M, Lerondel S, Majoral C, Diot P, Racineux JL, Lemarie E (2008) Aerosolized chemotherapy. J Aerosol Med Pulm Drug Deliv 21: 61-70.
12. Garcia-Manero G, Gore SD, Cogle C, Ward R, Shi T, Macbeth KJ, Laille E, Giordano H, Sakoian S, Jabbour E, Kantarjian H, Skikne B (2011) Phase I study of oral azacitidine in myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia. J Clin Oncol 29: 2521-2527.
13. Gore SD, Baylin S, Sugar E, Carraway H, Miller CB, Carducci M, Grever M, Galm O, Dauses T, Karp JE, Rudek MA, Zhao M, Smith BD, Manning J, Jiemjit A, Dover G, Mays A, Zwiebel J, Murgo A, Weng LJ, Herman JG (2006) Combined DNA methyltransferase and histone deacetylase inhibition in the treatment of myeloid neoplasms. Cancer Res 66: 6361-6369.
14. Herman JG, Baylin SB (2003) Gene silencing in cancer in association with promoter hypermethylation. N Engl J Med 349: 2042-2054.
15. Ho DH, Frei III E (1971) Clinical pharmacology of 1-beta-D- arabinofuranosyl cytosine. Clin Pharmacol Ther 12: 944-954.
16. Jones PA, Baylin SB (2002) The fundamental role of epigenetic events in cancer. Nat Rev Genet 3: 415-428.
17. Juergens RA, Wrangle J, Vendetti FP, Murphy SC, Zhao M, Coleman B, Sebree R, Rodgers K, Hooker CM, Franco N, Lee B, Tsai S, Delgado IE, Rudek MA, Belinsky SA, Herman JG, Baylin SB, Brock MV, Rudin CM (2011) Combination epigenetic therapy has efficacy in patients with refractory advanced non-small cell lung cancer. Cancer Discov 1: 598-607.
18. Kissinger LD, Stemm NL (1986) Determination of the antileukemia agents cytarabine and azacitidine and their respective degradation products by high-performance liquid chromatography. J Chromatogr 353: 309-318.
19. Kuehl PJ, Anderson TL, Candelaria G, Gershman B, Harlin K, Hesterman JY, Holmes T, Hoppin J, Lackas C, Norenberg JP, Yu H, McDonald JD (2012) Regional particle size dependent deposition of inhaled aerosols in rats and mice. Inhal Toxicol 24: 27-35.
20. Lemarie E, Vecellio L, Hureaux J, Prunier C, Valat C, Grimbert D, Boidron-Celle M, Giraudeau B, le Pape A, Pichon E, Diot P, el Houfia A, Gagnadoux F (2011) Aerosolized gemcitabine in patients with carcinoma of the lung: feasibility and safety study. J Aerosol Med Pulm Drug Deliv 24: 261-270.
21. Leng S, Do K, Yingling CM, Picchi MA, Wolf HJ, Kennedy TC, Feser WJ, Baron AE, Franklin WA, Brock MV, Herman JG, Baylin SB, Byers T, Stidley CA, Belinsky SA (2012) Defining a gene promoter methylation signature in sputum for lung cancer risk assessment. Clin Cancer Res 18: 3387-3395.
22. Mahesh S, Saxena A, Qiu X, Perez-Soler R, Zou Y (2010) Intratracheally administered 5-azacytidine is effective against orthotopic human lung cancer xenograft models and devoid of important systemic toxicity. Clin Lung Cancer 11: 405-411.
23. Mahfouz RZ, Jankowska A, Ebrahem Q, Gu X, Visconte V, Tabarroki A, Terse P, Covey J, Chan K, Ling Y, Engelke KJ, Sekeres MA, Tiu R, Maciejewski J, Radivoyevitch T, Saunthararajah Y (2013) Increased CDA expression/activity in males contributes to decreased cytidine analog half-life and likely contributes to worse outcomes with 5-azacytidine or decitabine therapy. Clin Cancer Res 19: 938-948.
24. March TH, Marron-Terada PG, Belinsky SA (2001) Refinement of an orthotopic lung cancer model in the nude rat. Vet Pathol 38: 483-490.
25. Mebratu YA, Dickey BF, Evans C, Tesfaigzi Y (2008) The BH3-only protein Bik/Blk/Nbk inhibits nuclear translocation of activated ERK1/2 to mediate IFNgamma-induced cell death. J Cell Biol 183: 429-439.
26. Meenach SA, Vogt FG, Anderson KW, Hilt JZ, McGarry RC, Mansour HM (2013) Design, physicochemical characterization, and optimization of organic solution advanced spray-dried inhalable dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylethanolamine poly(ethylene glycol) (DPPE-PEG) microparticles and nanoparticles for targeted respiratory nanomedicine delivery as dry powder inhalation aerosols. Int J Nanomed 8: 275-293.
27. Nanjwade BK, Adichwal SA, Gaikwad KR, Parikh KA, Manvi FV (2001) Pulmonary drug delivery: novel pharmaceutical technologies breathe new life into the lungs. PDA J Pharm Sci Technol 65: 513-534.
28. Silverman LR, Demakos EP, Peterson BL, Kornblith AB, Holland JC, Odchimar-Reissig R, Stone RM, Nelson D, Powell BL, DeCastro CM, Ellerton J, Larson RA, Schiffer CA, Holland JF (2002) Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B. J Clin Oncol 20: 2429-2440.
29. Tang X, Yin X, Xiang T, Li H, Li F, Chen L, Ren G (2012) Protocadherin 10 is frequently downregulated by promoter methylation and functions as a tumor suppressor gene in non-small cell lung cancer. Cancer Biomark 12: 11-19.
30. Tessema M, Klinge DM, Yingling CM, Do K, Van Neste L, Belinsky SA (2010) Re-expression of CXCL14, a common target for epigenetic silencing in lung cancer, induces tumor necrosis. Oncogene 29: 5159-5170.
31. Tessema M, Yu YY, Stidley CA, Machida EO, Schuebel KE, Baylin SB, Belinsky SA (2009) Concomitant promoter methylation of multiple genes in lung adenocarcinomas from current, former and never smokers. Carcinogenesis 30: 1132-1138.
32. Thiel CG (2002) Cascade impactor data and the lognormal distribution: nonlinear regression for a better fit. J Aerosol Med 15: 369-378.
33. Willis L, Hayes Jr D, Mansour HM (2012) Therapeutic liposomal dry powder inhalation aerosols for targeted lung delivery. Lung 190: 251-262.
34. Wittgen BP, Kunst PW, van der Born K, van Wijk AW, Perkins W, Pilkiewicz FG, Perez-Soler R, Nicholson S, Peters GJ, Postmus PE (2007) Phase I study of aerosolized SLIT cisplatin in the treatment of patients with carcinoma of the lung. Clin Cancer Res 13: 2414-2421.
35. Yang AS, Doshi KD, Choi SW, Mason JB, Mannari RK, Gharybian V, Luna R, Rashid A, Shen L, Estecio MR, Kantarjian HM, Garcia-Manero G, Issa JP (2006) DNA methylation changes after 5-aza-20-deoxycytidine therapy in patients with leukemia. Cancer Res 66: 5495-5503.