Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
International Journal of Oncology
Join Editorial Board Propose a Special Issue
Print ISSN: 1019-6439 Online ISSN: 1791-2423
Journal Cover
May-2015 Volume 46 Issue 5

Full Size Image

Cover Legend PDF

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
May-2015 Volume 46 Issue 5

Full Size Image

Cover Legend PDF

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

The epigenetic agents suberoylanilide hydroxamic acid and 5‑AZA‑2' deoxycytidine decrease cell proliferation, induce cell death and delay the growth of MiaPaCa2 pancreatic cancer cells in vivo

  • Authors:
    • Johana M. Susanto
    • Emily K. Colvin
    • Mark Pinese
    • David K. Chang
    • Marina Pajic
    • Amanda Mawson
    • C. Elizabeth Caldon
    • Elizabeth A. Musgrove
    • Susan M. Henshall
    • Robert L. Sutherland
    • Andrew V. Biankin
    • Christopher J. Scarlett
  • View Affiliations / Copyright

    Affiliations: Cancer Research Program, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia
  • Pages: 2223-2230
    |
    Published online on: February 16, 2015
       https://doi.org/10.3892/ijo.2015.2894
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Despite incremental advances in the diagnosis and treatment for pancreatic cancer (PC), the 5‑year survival rate remains <5%. Novel therapies to increase survival and quality of life for PC patients are desperately needed. Epigenetic thera­peutic agents such as histone deacetylase inhibitors (HDACi) and DNA methyltransferase inhibitors (DNMTi) have demonstrated therapeutic benefits in human cancer. We assessed the efficacy of these epigenetic therapeutic agents as potential therapies for PC using in vitro and in vivo models. Treatment with HDACi [suberoylanilide hydroxamic acid (SAHA)] and DNMTi [5‑AZA‑2' deoxycytidine (5‑AZA‑dc)] decreased cell proliferation in MiaPaCa2 cells, and SAHA treatment, with or without 5‑AZA‑dc, resulted in higher cell death and lower DNA synthesis compared to 5‑AZA‑dc alone and controls (DMSO). Further, combination treatment with SAHA and 5‑AZA‑dc significantly increased expression of p21WAF1, leading to G1 arrest. Treatment with epigenetic agents delayed tumour growth in vivo, but did not decrease growth of established pancreatic tumours. In conclusion, these data demonstrate a potential role for epigenetic modifier drugs for the management of PC, specifically in the chemoprevention of PC, in combination with other chemotherapeutic agents.
View Figures

Figure 1

Figure 2

View References

1 

Cancer Institute NSW. Cancer in New South Wales: Incidence, Mortality and Prevalence 2005. Cancer Institute NSW; Sydney: 2007

2 

National Cancer Institute: Cancer Trends Progress Report - 2007 Update. National Cancer Institute; Bethesda, MD: 2007

3 

National Cancer Institute. A Snapshot of Pancreatic Cancer. National Cancer Institute; Bethesda, MD: 2007

4 

Australian Institute of Health and Welfare (AIHW) and Australasian Association of Cancer Registries (AACR). Cancer in Australia: an overview, 2008. AIHW and AACR; Canberra: 2008

5 

American Cancer Society. Cancer Facts and Figures 2008. American Cancer Society; Atlanta, GA: 2008

6 

Jemal A, Siegel R, Ward E, Hao Y, Xu J and Thun MJ: Cancer statistics, 2009. CA Cancer J Clin. 59:225–249. 2009. View Article : Google Scholar : PubMed/NCBI

7 

American Cancer Society. Cancer Facts and Figures 2007. American Cancer Society; Atlanta, GA: 2007

8 

Von Hoff DD, Evans DB and Hruban RH: Pancreatic Cancer. 1st edition. Jones and Bartlett Publishers; Sudbury, MA: 2005

9 

Chang DK, Merrett ND and Biankin AV: NSW Pancreatic Cancer Network: Improving outcomes for operable pancreatic cancer: is access to safer surgery the problem? J Gastroenterol Hepatol. 23:1036–1045. 2008. View Article : Google Scholar : PubMed/NCBI

10 

Glaser KB: HDAC inhibitors: clinical update and mechanism-based potential. Biochem Pharmacol. 74:659–671. 2007. View Article : Google Scholar : PubMed/NCBI

11 

Duvic M, Talpur R, Ni X, et al: Phase 2 trial of oral vorinostat (suberoylanilide hydroxamic acid, SAHA) for refractory cutaneous T-cell lymphoma (CTCL). Blood. 109:31–39. 2007. View Article : Google Scholar

12 

Zhang C, Richon V, Ni X, Talpur R and Duvic M: Selective induction of apoptosis by histone deacetylase inhibitor SAHA in cutaneous T-cell lymphoma cells: relevance to mechanism of therapeutic action. J Invest Dermatol. 125:1045–1052. 2005. View Article : Google Scholar : PubMed/NCBI

13 

Gore SD: Combination therapy with DNA methyltransferase inhibitors in hematologic malignancies. Nat Clin Pract Oncol. 2(Suppl 1): S30–S35. 2005. View Article : Google Scholar : PubMed/NCBI

14 

Issa JP and Byrd JC: Decitabine in chronic leukemias. Semin Hematol. 42(Suppl 2): S43–S49. 2005. View Article : Google Scholar : PubMed/NCBI

15 

Batty N, Malouf GG and Issa JP: Histone deacetylase inhibitors as anti-neoplastic agents. Cancer Lett. 280:192–200. 2009. View Article : Google Scholar : PubMed/NCBI

16 

Flotho C, Claus R, Batz C, et al: The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia. 23:1019–1028. 2009. View Article : Google Scholar : PubMed/NCBI

17 

Laurenzana A, Petruccelli LA, Pettersson F, et al: Inhibition of DNA methyltransferase activates tumor necrosis factor alpha-induced monocytic differentiation in acute myeloid leukemia cells. Cancer Res. 69:55–64. 2009. View Article : Google Scholar : PubMed/NCBI

18 

Munster PN, Troso-Sandoval T, Rosen N, Rifkind R, Marks PA and Richon VM: The histone deacetylase inhibitor suberoylanilide hydroxamic acid induces differentiation of human breast cancer cells. Cancer Res. 61:8492–8497. 2001.PubMed/NCBI

19 

Shiozawa K, Nakanishi T, Tan M, et al: Preclinical studies of vorinostat (suberoylanilide hydroxamic acid) combined with cytosine arabinoside and etoposide for treatment of acute leukemias. Clin Cancer Res. 15:1698–1707. 2009. View Article : Google Scholar : PubMed/NCBI

20 

Xu WS, Parmigiani RB and Marks PA: Histone deacetylase inhibitors: molecular mechanisms of action. Oncogene. 26:5541–5552. 2007. View Article : Google Scholar : PubMed/NCBI

21 

Buchwald M, Krämer OH and Heinzel T: HDACi - targets beyond chromatin. Cancer Lett. 280:160–167. 2009. View Article : Google Scholar : PubMed/NCBI

22 

Nolan L, Johnson PW, Ganesan A, Packham G and Crabb SJ: Will histone deacetylase inhibitors require combination with other agents to fulfil their therapeutic potential? Br J Cancer. 99:689–694. 2008. View Article : Google Scholar : PubMed/NCBI

23 

Gui CY, Ngo L, Xu WS, Richon VM and Marks PA: Histone deacetylase (HDAC) inhibitor activation of p21WAF1 involves changes in promoter-associated proteins, including HDAC1. Proc Natl Acad Sci USA. 101:1241–1246. 2004. View Article : Google Scholar

24 

Arnold NB, Arkus N, Gunn J and Korc M: The histone deacetylase inhibitor suberoylanilide hydroxamic acid induces growth inhibition and enhances gemcitabine-induced cell death in pancreatic cancer. Clin Cancer Res. 13:18–26. 2007. View Article : Google Scholar : PubMed/NCBI

25 

Eyüpoglu IY, Hahnen E, Buslei R, et al: Suberoylanilide hydroxamic acid (SAHA) has potent anti-glioma properties in vitro, ex vivo and in vivo. J Neurochem. 93:992–999. 2005. View Article : Google Scholar : PubMed/NCBI

26 

Kumagai T, Wakimoto N, Yin D, et al: Histone deacetylase inhibitor, suberoylanilide hydroxamic acid (Vorinostat, SAHA) profoundly inhibits the growth of human pancreatic cancer cells. Int J Cancer. 121:656–665. 2007. View Article : Google Scholar : PubMed/NCBI

27 

Hurd PJ, Whitmarsh AJ, Baldwin GS, et al: Mechanism-based inhibition of C5-cytosine DNA methyltransferases by 2-H pyrimidinone. J Mol Biol. 286:389–401. 1999. View Article : Google Scholar : PubMed/NCBI

28 

Jones PA and Baylin SB: The fundamental role of epigenetic events in cancer. Nat Rev Genet. 3:415–428. 2002.PubMed/NCBI

29 

Jackson-Grusby L, Beard C, Possemato R, et al: Loss of genomic methylation causes p53-dependent apoptosis and epigenetic deregulation. Nat Genet. 27:31–39. 2001. View Article : Google Scholar : PubMed/NCBI

30 

Scott SA, Lakshimikuttysamma A, Sheridan DP, Sanche SE, Geyer CR and DeCoteau JF: Zebularine inhibits human acute myeloid leukemia cell growth in vitro in association with p15INK4B demethylation and reexpression. Exp Hematol. 35:263–273. 2007. View Article : Google Scholar : PubMed/NCBI

31 

Gilbert J, Gore SD, Herman JG and Carducci MA: The clinical application of targeting cancer through histone acetylation and hypomethylation. Clin Cancer Res. 10:4589–4596. 2004. View Article : Google Scholar : PubMed/NCBI

32 

Sato N, Fukushima N, Maehara N, et al: SPARC/osteonectin is a frequent target for aberrant methylation in pancreatic adenocarcinoma and a mediator of tumor-stromal interactions. Oncogene. 22:5021–5030. 2003. View Article : Google Scholar : PubMed/NCBI

33 

Sato N, Parker AR, Fukushima N, et al: Epigenetic inactivation of TFPI-2 as a common mechanism associated with growth and invasion of pancreatic ductal adenocarcinoma. Oncogene. 24:850–858. 2005. View Article : Google Scholar

34 

Fu B, Guo M, Wang S, et al: Evaluation of GATA-4 and GATA-5 methylation profiles in human pancreatic cancers indicate promoter methylation patterns distinct from other human tumor types. Cancer Biol Ther. 6:1546–1552. 2007. View Article : Google Scholar : PubMed/NCBI

35 

Abe T, Toyota M, Suzuki H, et al: Upregulation of BNIP3 by 5-aza-2′-deoxycytidine sensitizes pancreatic cancer cells to hypoxia-mediated cell death. J Gastroenterol. 40:504–510. 2005. View Article : Google Scholar : PubMed/NCBI

36 

Yamada N, Nishida Y, Tsutsumida H, et al: MUC1 expression is regulated by DNA methylation and histone H3 lysine 9 modification in cancer cells. Cancer Res. 68:2708–2716. 2008. View Article : Google Scholar : PubMed/NCBI

37 

Yamada N, Hamada T, Goto M, et al: MUC2 expression is regulated by histone H3 modification and DNA methylation in pancreatic cancer. Int J Cancer. 119:1850–1857. 2006. View Article : Google Scholar : PubMed/NCBI

38 

Vincent A, Ducourouble MP and Van Seuningen I: Epigenetic regulation of the human mucin gene MUC4 in epithelial cancer cell lines involves both DNA methylation and histone modifications mediated by DNA methyltransferases and histone deacetylases. FASEB J. 22:3035–3045. 2008. View Article : Google Scholar : PubMed/NCBI

39 

Yonezawa S, Goto M, Yamada N, Higashi M and Nomoto M: Expression profiles of MUC1, MUC2, and MUC4 mucins in human neoplasms and their relationship with biological behavior. Proteomics. 8:3329–3341. 2008. View Article : Google Scholar : PubMed/NCBI

40 

Omura N and Goggins M: Epigenetics and epigenetic alterations in pancreatic cancer. Int J Clin Exp Pathol. 2:310–326. 2009.PubMed/NCBI

41 

Furukawa T, Duguid WP, Rosenberg L, Viallet J, Galloway DA and Tsao MS: Long-term culture and immortalization of epithelial cells from normal adult human pancreatic ducts transfected by the E6E7 gene of human papilloma virus 16. Am J Pathol. 148:1763–1770. 1996.PubMed/NCBI

42 

Vonlaufen A, Joshi S, Qu C, et al: Pancreatic stellate cells: partners in crime with pancreatic cancer cells. Cancer Res. 68:2085–2093. 2008. View Article : Google Scholar : PubMed/NCBI

43 

Probst AV, Dunleavy E and Almouzni G: Epigenetic inheritance during the cell cycle. Nat Rev Mol Cell Biol. 10:192–206. 2009. View Article : Google Scholar : PubMed/NCBI

44 

Missiaglia E, Donadelli M, Palmieri M, Crnogorac-Jurcevic T, Scarpa A and Lemoine NR: Growth delay of human pancreatic cancer cells by methylase inhibitor 5-aza-2′-deoxycytidine treatment is associated with activation of the interferon signalling pathway. Oncogene. 24:199–211. 2005. View Article : Google Scholar : PubMed/NCBI

45 

Bolden JE, Peart MJ and Johnstone RW: Anticancer activities of histone deacetylase inhibitors. Nat Rev Drug Discov. 5:769–784. 2006. View Article : Google Scholar : PubMed/NCBI

46 

Butler LM, Agus DB, Scher HI, et al: Suberoylanilide hydroxamic acid, an inhibitor of histone deacetylase, suppresses the growth of prostate cancer cells in vitro and in vivo. Cancer Res. 60:5165–5170. 2000.PubMed/NCBI

47 

Butler LM, Zhou X, Xu WS, et al: The histone deacetylase inhibitor SAHA arrests cancer cell growth, up-regulates thioredoxin-binding protein-2, and down-regulates thioredoxin. Proc Natl Acad Sci USA. 99:11700–11705. 2002. View Article : Google Scholar : PubMed/NCBI

48 

Marks PA and Breslow R: Dimethyl sulfoxide to vorinostat: development of this histone deacetylase inhibitor as an anticancer drug. Nat Biotechnol. 25:84–90. 2007. View Article : Google Scholar : PubMed/NCBI

49 

Henderson C, Mizzau M, Paroni G, Maestro R, Schneider C and Brancolini C: Role of caspases, Bid, and p53 in the apoptotic response triggered by histone deacetylase inhibitors trichostatin-A (TSA) and suberoylanilide hydroxamic acid (SAHA). J Biol Chem. 278:12579–12589. 2003. View Article : Google Scholar : PubMed/NCBI

50 

Egger G, Liang G, Aparicio A and Jones PA: Epigenetics in human disease and prospects for epigenetic therapy. Nature. 429:457–463. 2004. View Article : Google Scholar : PubMed/NCBI

51 

Polo SE and Almouzni G: Histone metabolic pathways and chromatin assembly factors as proliferation markers. Cancer Lett. 220:1–9. 2005. View Article : Google Scholar : PubMed/NCBI

52 

Koundrioukoff S, Polo S and Almouzni G: Interplay between chromatin and cell cycle checkpoints in the context of ATR/ATM-dependent checkpoints. DNA Repair (Amst). 3:969–978. 2004. View Article : Google Scholar

53 

Graham JS, Kaye SB and Brown R: The promises and pitfalls of epigenetic therapies in solid tumours. Eur J Cancer. 45:1129–1136. 2009. View Article : Google Scholar : PubMed/NCBI

54 

Polo SE and Almouzni G: DNA damage leaves its mark on chromatin. Cell Cycle. 6:2355–2359. 2007. View Article : Google Scholar : PubMed/NCBI

55 

Vrana JA, Decker RH, Johnson CR, et al: Induction of apoptosis in U937 human leukemia cells by suberoylanilide hydroxamic acid (SAHA) proceeds through pathways that are regulated by Bcl-2/Bcl-XL, c-Jun, and p21CIP1, but independent of p53. Oncogene. 18:7016–7025. 1999. View Article : Google Scholar : PubMed/NCBI

56 

Abbas T and Dutta A: p21 in cancer: intricate networks and multiple activities. Nat Rev Cancer. 9:400–414. 2009. View Article : Google Scholar : PubMed/NCBI

57 

Mills J, Hricik T, Siddiqi S and Matushansky I: Chromatin structure predicts epigenetic therapy responsiveness in sarcoma. Mol Cancer Ther. 10:313–324. 2011. View Article : Google Scholar : PubMed/NCBI

58 

Yin D, Ong JM, Hu J, et al: Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor: effects on gene expression and growth of glioma cells in vitro and in vivo. Clin Cancer Res. 13:1045–1052. 2007. View Article : Google Scholar : PubMed/NCBI

59 

Vijayaraghavalu S, Dermawan JK, Cheriyath V and Labhasetwar V: Highly synergistic effect of sequential treatment with epigenetic and anticancer drugs to overcome drug resistance in breast cancer cells is mediated via activation of p21 gene expression leading to G2/M cycle arrest. Mol Pharm. 10:337–352. 2013. View Article : Google Scholar :

60 

Carew JS, Nawrocki ST and Cleveland JL: Modulating autophagy for therapeutic benefit. Autophagy. 3:464–467. 2007. View Article : Google Scholar : PubMed/NCBI

61 

Robert T, Vanoli F, Chiolo I, et al: HDACs link the DNA damage response, processing of double-strand breaks and autophagy. Nature. 471:74–79. 2011. View Article : Google Scholar : PubMed/NCBI

62 

Dokmanovic M, Perez G, Xu W, et al: Histone deacetylase inhibitors selectively suppress expression of HDAC7. Mol Cancer Ther. 6:2525–2534. 2007. View Article : Google Scholar : PubMed/NCBI

63 

Mitsiades CS, Mitsiades NS, McMullan CJ, et al: Transcriptional signature of histone deacetylase inhibition in multiple myeloma: biological and clinical implications. Proc Natl Acad Sci USA. 101:540–545. 2004. View Article : Google Scholar :

64 

Cooper AL, Greenberg VL, Lancaster PS, van Nagell JR Jr, Zimmer SG and Modesitt SC: In vitro and in vivo histone deacetylase inhibitor therapy with suberoylanilide hydroxamic acid (SAHA) and paclitaxel in ovarian cancer. Gynecol Oncol. 104:596–601. 2007. View Article : Google Scholar

65 

Nimmanapalli R, Fuino L, Stobaugh C, Richon V and Bhalla K: Cotreatment with the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) enhances imatinib-induced apoptosis of Bcr-Abl-positive human acute leukemia cells. Blood. 101:3236–3239. 2003. View Article : Google Scholar

66 

Holzman DC: Pancreatic cancer: will incremental advances begin to make a difference? J Natl Cancer Inst. 102:1821–1823. 2010. View Article : Google Scholar : PubMed/NCBI

67 

Neoptolemos JP, Dunn JA, Stocken DD, et al: Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: a randomised controlled trial. Lancet. 358:1576–1585. 2001. View Article : Google Scholar : PubMed/NCBI

68 

Neoptolemos JP, Stocken DD, Bassi C, et al: Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial. JAMA. 304:1073–1081. 2010. View Article : Google Scholar : PubMed/NCBI

69 

O’Reilly EM: Refinement of adjuvant therapy for pancreatic cancer. JAMA. 304:1124–1125. 2010. View Article : Google Scholar

70 

Mohammed A, Janakiram NB, Li Q, et al: The epidermal growth factor receptor inhibitor gefitinib prevents the progression of pancreatic lesions to carcinoma in a conditional LSL-KrasG12D/+ transgenic mouse model. Cancer Prev Res (Phila). 3:1417–1426. 2010. View Article : Google Scholar

71 

Appleton K, Mackay HJ, Judson I, et al: Phase I and pharmacodynamic trial of the DNA methyltransferase inhibitor decitabine and carboplatin in solid tumors. J Clin Oncol. 25:4603–4609. 2007. View Article : Google Scholar : PubMed/NCBI

72 

Venturelli S, Berger A, Weiland T, et al: Dual antitumour effect of 5-azacytidine by inducing a breakdown of resistance-mediating factors and epigenetic modulation. Gut. 60:156–165. 2011. View Article : Google Scholar

73 

Shakya R, Gonda T, Quante M, et al: Hypomethylating therapy in an aggressive stroma-rich model of pancreatic carcinoma. Cancer Res. 73:885–896. 2013. View Article : Google Scholar :

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Susanto JM, Colvin EK, Pinese M, Chang DK, Pajic M, Mawson A, Caldon CE, Musgrove EA, Henshall SM, Sutherland RL, Sutherland RL, et al: The epigenetic agents suberoylanilide hydroxamic acid and 5‑AZA‑2' deoxycytidine decrease cell proliferation, induce cell death and delay the growth of MiaPaCa2 pancreatic cancer cells in vivo. Int J Oncol 46: 2223-2230, 2015.
APA
Susanto, J.M., Colvin, E.K., Pinese, M., Chang, D.K., Pajic, M., Mawson, A. ... Scarlett, C.J. (2015). The epigenetic agents suberoylanilide hydroxamic acid and 5‑AZA‑2' deoxycytidine decrease cell proliferation, induce cell death and delay the growth of MiaPaCa2 pancreatic cancer cells in vivo. International Journal of Oncology, 46, 2223-2230. https://doi.org/10.3892/ijo.2015.2894
MLA
Susanto, J. M., Colvin, E. K., Pinese, M., Chang, D. K., Pajic, M., Mawson, A., Caldon, C. E., Musgrove, E. A., Henshall, S. M., Sutherland, R. L., Biankin, A. V., Scarlett, C. J."The epigenetic agents suberoylanilide hydroxamic acid and 5‑AZA‑2' deoxycytidine decrease cell proliferation, induce cell death and delay the growth of MiaPaCa2 pancreatic cancer cells in vivo". International Journal of Oncology 46.5 (2015): 2223-2230.
Chicago
Susanto, J. M., Colvin, E. K., Pinese, M., Chang, D. K., Pajic, M., Mawson, A., Caldon, C. E., Musgrove, E. A., Henshall, S. M., Sutherland, R. L., Biankin, A. V., Scarlett, C. J."The epigenetic agents suberoylanilide hydroxamic acid and 5‑AZA‑2' deoxycytidine decrease cell proliferation, induce cell death and delay the growth of MiaPaCa2 pancreatic cancer cells in vivo". International Journal of Oncology 46, no. 5 (2015): 2223-2230. https://doi.org/10.3892/ijo.2015.2894
Copy and paste a formatted citation
x
Spandidos Publications style
Susanto JM, Colvin EK, Pinese M, Chang DK, Pajic M, Mawson A, Caldon CE, Musgrove EA, Henshall SM, Sutherland RL, Sutherland RL, et al: The epigenetic agents suberoylanilide hydroxamic acid and 5‑AZA‑2' deoxycytidine decrease cell proliferation, induce cell death and delay the growth of MiaPaCa2 pancreatic cancer cells in vivo. Int J Oncol 46: 2223-2230, 2015.
APA
Susanto, J.M., Colvin, E.K., Pinese, M., Chang, D.K., Pajic, M., Mawson, A. ... Scarlett, C.J. (2015). The epigenetic agents suberoylanilide hydroxamic acid and 5‑AZA‑2' deoxycytidine decrease cell proliferation, induce cell death and delay the growth of MiaPaCa2 pancreatic cancer cells in vivo. International Journal of Oncology, 46, 2223-2230. https://doi.org/10.3892/ijo.2015.2894
MLA
Susanto, J. M., Colvin, E. K., Pinese, M., Chang, D. K., Pajic, M., Mawson, A., Caldon, C. E., Musgrove, E. A., Henshall, S. M., Sutherland, R. L., Biankin, A. V., Scarlett, C. J."The epigenetic agents suberoylanilide hydroxamic acid and 5‑AZA‑2' deoxycytidine decrease cell proliferation, induce cell death and delay the growth of MiaPaCa2 pancreatic cancer cells in vivo". International Journal of Oncology 46.5 (2015): 2223-2230.
Chicago
Susanto, J. M., Colvin, E. K., Pinese, M., Chang, D. K., Pajic, M., Mawson, A., Caldon, C. E., Musgrove, E. A., Henshall, S. M., Sutherland, R. L., Biankin, A. V., Scarlett, C. J."The epigenetic agents suberoylanilide hydroxamic acid and 5‑AZA‑2' deoxycytidine decrease cell proliferation, induce cell death and delay the growth of MiaPaCa2 pancreatic cancer cells in vivo". International Journal of Oncology 46, no. 5 (2015): 2223-2230. https://doi.org/10.3892/ijo.2015.2894
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team