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International Journal of Oncology
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Print ISSN: 1019-6439 Online ISSN: 1791-2423
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August-2016 Volume 49 Issue 2

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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.

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

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

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

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

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Article

Naltrexone at low doses upregulates a unique gene expression not seen with normal doses: Implications for its use in cancer therapy

  • Authors:
    • Wai M. Liu
    • Katherine A. Scott
    • Jayne L. Dennis
    • Elwira Kaminska
    • Alan J. Levett
    • Angus G. Dalgleish
  • View Affiliations / Copyright

    Affiliations: Department of Oncology, Institute for Infection and Immunity, St. George's University of London, London SW17 0RE, UK
  • Pages: 793-802
    |
    Published online on: June 7, 2016
       https://doi.org/10.3892/ijo.2016.3567
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Abstract

It has been reported that lower doses of the opioid antagonist naltrexone are able to reduce tumour growth by interfering with cell signalling as well as by modifying the immune system. We have evaluated the gene expression profile of a cancer cell line after treatment with low-dose naltrexone (LDN), and assessed the effect that adapting treatment schedules with LDN may have on enhancing efficacy. LDN had a selective impact on genes involved with cell cycle regulation and immune modulation. Similarly, the pro-apoptotic genes BAD and BIK1 were increased only after LDN. Continuous treatment with LDN had little effect on growth in different cell lines; however, altering the treatment schedule to include a phase of culture in the absence of drug following an initial round of LDN treatment, resulted in enhanced cell killing. Furthermore, cells pre-treated with LDN were more sensitive to the cytotoxic effects of a number of common chemotherapy agents. For example, priming HCT116 with LDN before treatment with oxaliplatin significantly increased cell killing to 49±7.0 vs. 14±2.4% in cultures where priming was not used. Interestingly, priming with NTX before oxaliplatin resulted in just 32±1.8% cell killing. Our data support further the idea that LDN possesses anticancer activity, which can be improved by modifying the treatment schedule.
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1 

McLaughlin PJ and Zagon IS: Duration of opioid receptor blockade determines biotherapeutic response. Biochem Pharmacol. 97:236–246. 2015. View Article : Google Scholar : PubMed/NCBI

2 

Tegeder I and Geisslinger G: Opioids as modulators of cell death and survival - unraveling mechanisms and revealing new indications. Pharmacol Rev. 56:351–369. 2004. View Article : Google Scholar : PubMed/NCBI

3 

Afsharimani B, Cabot P and Parat MO: Morphine and tumor growth and metastasis. Cancer Metastasis Rev. 30:225–238. 2011. View Article : Google Scholar : PubMed/NCBI

4 

Gach K, Szemraj J, Stasikowska-Kanicka O, Danilewicz M and Janecka A: Opioid-receptor gene expression and localization in cancer cells. Cent Eur J Biol. 6:10–15. 2011.

5 

Bimonte S, Barbieri A, Palma G and Arra C: The role of morphine in animal models of human cancer: Does morphine promote or inhibit the tumor growth? BioMed Res Int. 2013:2581412013. View Article : Google Scholar : PubMed/NCBI

6 

Kim MS, Cheong YP, So HS, Lee KM, Kim TY, Oh J, Chung YT, Son Y, Kim BR and Park R: Protective effects of morphine in peroxynitrite-induced apoptosis of primary rat neonatal astrocytes: Potential involvement of G protein and phosphatidylinositol 3-kinase (PI3 kinase). Biochem Pharmacol. 61:779–786. 2001. View Article : Google Scholar : PubMed/NCBI

7 

Cui Y, Zhang XQ, Cui Y, Xin WJ, Jing J and Liu XG: Activation of phosphatidylinositol 3-kinase/Akt-mammalian target of Rapamycin signaling pathway in the hippocampus is essential for the acquisition of morphine-induced place preference in rats. Neuroscience. 171:134–143. 2010. View Article : Google Scholar : PubMed/NCBI

8 

Gach K, Wyrębska A, Fichna J and Janecka A: The role of morphine in regulation of cancer cell growth. Naunyn Schmiedebergs Arch Pharmacol. 384:221–230. 2011. View Article : Google Scholar : PubMed/NCBI

9 

Ishikawa M, Tanno K, Kamo A, Takayanagi Y and Sasaki K: Enhancement of tumor growth by morphine and its possible mechanism in mice. Biol Pharm Bull. 16:762–766. 1993. View Article : Google Scholar : PubMed/NCBI

10 

Boland JW, McWilliams K, Ahmedzai SH and Pockley AG: Effects of opioids on immunologic parameters that are relevant to anti-tumour immune potential in patients with cancer: A systematic literature review. Br J Cancer. 111:866–873. 2014. View Article : Google Scholar : PubMed/NCBI

11 

Liu WM: Enhancing the cytotoxic activity of novel targeted therapies - is there a role for a combinatorial approach? Curr Clin Pharmacol. 3:108–117. 2008. View Article : Google Scholar : PubMed/NCBI

12 

Liu WM, Laux H, Henry JY, Bolton TB, Dalgleish AG and Galustian C: A microarray study of altered gene expression in colorectal cancer cells after treatment with immunomodulatory drugs: Differences in action in vivo and in vitro. Mol Biol Rep. 37:1801–1814. 2010. View Article : Google Scholar

13 

Liu WM, Dennis JL, Fowler DW and Dalgleish AG: The gene expression profile of unstimulated dendritic cells can be used as a predictor of function. Int J Cancer. 130:979–990. 2012. View Article : Google Scholar

14 

Liu WM, Dennis JL, Gravett AM, Chanthirakumar C, Kaminska E, Coulton G, Fowler DW, Bodman-Smith M and Dalgleish AG: Supernatants derived from chemotherapy-treated cancer cell lines can modify angiogenesis. Br J Cancer. 106:896–903. 2012. View Article : Google Scholar : PubMed/NCBI

15 

Scott KA, Dennis JL, Dalgleish AG and Liu WM: Inhibiting heat shock proteins can potentiate the cytotoxic effect of cannabidiol in human glioma cells. Anticancer Res. 35:5827–5837. 2015.PubMed/NCBI

16 

Liu WM, Gravett AM and Dalgleish AG: The antimalarial agent artesunate possesses anticancer properties that can be enhanced by combination strategies. Int J Cancer. 128:1471–1480. 2011. View Article : Google Scholar

17 

Liu WM, Fowler DW, Smith P and Dalgleish AG: Pre-treatment with chemotherapy can enhance the antigenicity and immunogenicity of tumours by promoting adaptive immune responses. Br J Cancer. 102:115–123. 2010. View Article : Google Scholar :

18 

Liu WM, Lawrence AJ and Joel SP: The importance of drug scheduling and recovery phases in determining drug activity. Improving etoposide efficacy in BCR-ABL-positive CML cells. Eur J Cancer. 38:842–850. 2002. View Article : Google Scholar : PubMed/NCBI

19 

Scott KA, Shah S, Dalgleish AG and Liu WM: Enhancing the activity of cannabidiol and other cannabinoids in vitro through modifications to drug combinations and treatment schedules. Anticancer Res. 33:4373–4380. 2013.PubMed/NCBI

20 

Sobel H and Bonorris G: Effect of morphine on rats bearing Walker carcinosarcoma 256. Nature. 196:896–897. 1962. View Article : Google Scholar : PubMed/NCBI

21 

Sacerdote P: Opioids and the immune system. Palliat Med. 20(Suppl 1): S9–S15. 2006.PubMed/NCBI

22 

Meriney SD, Gray DB and Pilar G: Morphine-induced delay of normal cell death in the avian ciliary ganglion. Science. 228:1451–1453. 1985. View Article : Google Scholar : PubMed/NCBI

23 

Liu WM and Dalgleish AG: The potential beneficial effects of drugs on the immune response to vaccination. Semin Oncol. 39:340–347. 2012. View Article : Google Scholar : PubMed/NCBI

24 

Pietenpol JA and Stewart ZA: Cell cycle checkpoint signaling: Cell cycle arrest versus apoptosis. Toxicology. 181–182:475–481. 2002. View Article : Google Scholar

25 

Shapiro GI and Harper JW: Anticancer drug targets: Cell cycle and checkpoint control. J Clin Invest. 104:1645–1653. 1999. View Article : Google Scholar : PubMed/NCBI

26 

Waldman T, Zhang Y, Dillehay L, Yu J, Kinzler K, Vogelstein B and Williams J: Cell-cycle arrest versus cell death in cancer therapy. Nat Med. 3:1034–1036. 1997. View Article : Google Scholar : PubMed/NCBI

27 

Zagon IS and McLaughlin PJ: Naltrexone modulates tumor response in mice with neuroblastoma. Science. 221:671–673. 1983. View Article : Google Scholar : PubMed/NCBI

28 

Donahue RN, McLaughlin PJ and Zagon IS: Low-dose naltrexone targets the opioid growth factor-opioid growth factor receptor pathway to inhibit cell proliferation: Mechanistic evidence from a tissue culture model. Exp Biol Med (Maywood). 236:1036–1050. 2011. View Article : Google Scholar

29 

Tudor G, Aguilera A, Halverson DO, Laing ND and Sausville EA: Susceptibility to drug-induced apoptosis correlates with differential modulation of Bad, Bcl-2 and Bcl-xL protein levels. Cell Death Differ. 7:574–586. 2000. View Article : Google Scholar : PubMed/NCBI

30 

Makin G and Dive C: Recent advances in understanding apoptosis: New therapeutic opportunities in cancer chemotherapy. Trends Mol Med. 9:251–255. 2003. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Liu WM, Scott KA, Dennis JL, Kaminska E, Levett AJ and Dalgleish AG: Naltrexone at low doses upregulates a unique gene expression not seen with normal doses: Implications for its use in cancer therapy. Int J Oncol 49: 793-802, 2016.
APA
Liu, W.M., Scott, K.A., Dennis, J.L., Kaminska, E., Levett, A.J., & Dalgleish, A.G. (2016). Naltrexone at low doses upregulates a unique gene expression not seen with normal doses: Implications for its use in cancer therapy. International Journal of Oncology, 49, 793-802. https://doi.org/10.3892/ijo.2016.3567
MLA
Liu, W. M., Scott, K. A., Dennis, J. L., Kaminska, E., Levett, A. J., Dalgleish, A. G."Naltrexone at low doses upregulates a unique gene expression not seen with normal doses: Implications for its use in cancer therapy". International Journal of Oncology 49.2 (2016): 793-802.
Chicago
Liu, W. M., Scott, K. A., Dennis, J. L., Kaminska, E., Levett, A. J., Dalgleish, A. G."Naltrexone at low doses upregulates a unique gene expression not seen with normal doses: Implications for its use in cancer therapy". International Journal of Oncology 49, no. 2 (2016): 793-802. https://doi.org/10.3892/ijo.2016.3567
Copy and paste a formatted citation
x
Spandidos Publications style
Liu WM, Scott KA, Dennis JL, Kaminska E, Levett AJ and Dalgleish AG: Naltrexone at low doses upregulates a unique gene expression not seen with normal doses: Implications for its use in cancer therapy. Int J Oncol 49: 793-802, 2016.
APA
Liu, W.M., Scott, K.A., Dennis, J.L., Kaminska, E., Levett, A.J., & Dalgleish, A.G. (2016). Naltrexone at low doses upregulates a unique gene expression not seen with normal doses: Implications for its use in cancer therapy. International Journal of Oncology, 49, 793-802. https://doi.org/10.3892/ijo.2016.3567
MLA
Liu, W. M., Scott, K. A., Dennis, J. L., Kaminska, E., Levett, A. J., Dalgleish, A. G."Naltrexone at low doses upregulates a unique gene expression not seen with normal doses: Implications for its use in cancer therapy". International Journal of Oncology 49.2 (2016): 793-802.
Chicago
Liu, W. M., Scott, K. A., Dennis, J. L., Kaminska, E., Levett, A. J., Dalgleish, A. G."Naltrexone at low doses upregulates a unique gene expression not seen with normal doses: Implications for its use in cancer therapy". International Journal of Oncology 49, no. 2 (2016): 793-802. https://doi.org/10.3892/ijo.2016.3567
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