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Central European Journal of Biology

, Volume 7, Issue 3, pp 411–418 | Cite as

Opioid-regulated pro- and anti-apoptotic gene expression in cancer cells

  • Katarzyna Gach
  • Anna Wyrębska
  • Janusz Szemraj
  • Anna JaneckaEmail author
Communication
  • 84 Downloads

Abstract

Morphine, as well as opioid peptides, are well-known powerful analgesics. In addition to their use in the treatment of pain, opioids appear to be important in the growth regulation of neoplastic tissue. However, little is known on the influence of opioid peptides on apoptosis modulation in cancer cells. In the present study, we evaluated the effect of the µ-opioid receptor (MOR)-selective peptide, morphiceptin and its two synthetic analogs, on mRNA expression and protein levels of some crucial factors involved in apoptosis in three human cancer cell lines: MCF-7, HT-29, and SH-SY5Y. Using real-time PCR and ELISA assays, we have shown that the selected opioid peptides enhanced apoptosis of cancer cells by increasing the expression of pro-apoptoticc Bax and caspase-3, and decreasing expression of anti-apoptotic Bcl-2. Additionally, flow cytometry analysis performed on MCF-7 cells treated with annexin V/propidium iodide confirmed that the tested opioid peptides induced apoptosis in cancer cells. However, induction of apoptosis was not reversed by the opioid antagonist, naloxone, which suggests that this process is not mediated by the opioid receptors.

Keywords

Opioid peptides Apoptosis Pro-apoptotic genes Anti-apoptotic genes 

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References

  1. [1]
    Ashkenazi A., Dixit V.M., Apoptosis control by death and decoy receptors, Curr. Opin. Cell. Biol., 1999, 11, 255–260PubMedCrossRefGoogle Scholar
  2. [2]
    Cory S., Adams J.M., The Bcl2 family: regulators of the cellular life-or-death switch, Nat. Rev. Cancer, 2002, 2, 647–656PubMedCrossRefGoogle Scholar
  3. [3]
    Green D.R., Reed J.C., Mitochondria and apoptosis, Science, 1998, 281, 1309–1312PubMedCrossRefGoogle Scholar
  4. [4]
    Hengartner M.O., The biochemistry of apoptosis, Nature, 2000, 407, 770–776PubMedCrossRefGoogle Scholar
  5. [5]
    Tegeder I., Geisslinger G., Opioids as modulators of cell death and survival-unraveling mechanisms and revealing new indications, Pharmacol. Rev., 2004, 56, 351–369PubMedCrossRefGoogle Scholar
  6. [6]
    Gach K., Szemraj J., Stasikowska-Kanicka O., Danilewicz M., Janecka A., Opioid-receptor gene expression and localization in cancer cells, Cent Eur J Biol, 2011, 6, 10–15CrossRefGoogle Scholar
  7. [7]
    Fichna J., do-Rego J.C., Chung N.N., Lemieux C., Schiller P.W., Poels J., et al., Synthesis and characterization of potent and selective muopioid receptor antagonists, [Dmt(1), D-2-Nal(4)] endomorphin-1 (Antanal-1) and [Dmt(1), D-2-Nal(4)]endomorphin-2 (Antanal-2), J. Med. Chem., 2007, 50, 512–520PubMedCrossRefGoogle Scholar
  8. [8]
    Winer J., Jung C.K., Shackel I., Williams P.M., Development and validation of real-time quantitative reverse transcriptase-polymerase chain reaction for monitoring gene expression in cardiac myocytes in vitro, Anal Biochem, 1999, 270, 41–49PubMedCrossRefGoogle Scholar
  9. [9]
    van Engeland M., Nieland L.J., Ramaekers F.C., Schutte B., Reutelingsperger C.P., Annexin V-affinity assay: a review on an apoptosis detection system based on phosphatidylserine exposure, Cytometry, 1998, 31, 1–9PubMedCrossRefGoogle Scholar
  10. [10]
    Hanahan D., Weinberg R.A., The hallmarks of cancer, Cell, 2000, 100, 57–70PubMedCrossRefGoogle Scholar
  11. [11]
    Kaufmann S.H., Hengartner M.O., Programmed cell death: alive and well in the new millennium, Trends Cell. Biol., 2001, 11, 526–534PubMedCrossRefGoogle Scholar
  12. [12]
    Sueoka E., Sueoka N., Kai Y., Okabe S., Suganuma M., Kanematsu K., et al., Anticancer activity of morphine and its synthetic derivative, KT-90, mediated through apoptosis and inhibition of NF-kappaB activation, Biochem. Biophys. Res. Commun., 1998, 252, 566–570PubMedCrossRefGoogle Scholar
  13. [13]
    Hatsukari I., Hitosugi N., Matsumoto I., Nagasaka H., Sakagami H., Induction of early apoptosis marker by morphine in human lung and breast carcinoma cell lines, Anticancer. Res., 2003, 23, 2413–2417PubMedGoogle Scholar
  14. [14]
    Kawase M., Sakagami H., Furuya K., Kikuchi H., Nishikawa H., Motohashi N., et al., Cell deathinducing activity of opiates in human oral tumor cell lines, Anticancer. Res., 2002, 22, 211–214PubMedGoogle Scholar
  15. [15]
    Lin X., Chen Q., Xue L.Y., Ma X.J., Wang R., Endomorphins, endogenous opioid peptides, induce apoptosis in human leukemia HL-60 cells, Can. J. Physiol. Pharmacol., 2004, 82, 1018–1025PubMedCrossRefGoogle Scholar
  16. [16]
    Zagon I.S., McLaughlin P.J., Opioids and the apoptotic pathway in human cancer cells, Neuropeptides., 2003, 37, 79–88PubMedCrossRefGoogle Scholar
  17. [17]
    Sabourin J.C., Martin A., Baruch J., Truc J.B., Gompel A., Poitout P., bcl-2 expression in normal breast tissue during the menstrual cycle, Int. J. Cancer., 1994, 59, 1–6PubMedCrossRefGoogle Scholar
  18. [18]
    Cho M.Y., Park S.Y., Park S., Lee Y.R., Han G.D., Kim J.A., Geranyl derivative of phloroacetophenone induces cancer cell-specific apoptosis through Baxmediated mitochondrial pathway in MCF-7 human breast cancer cells, Biol. Pharm. Bull., 2012, 35, 98–104PubMedCrossRefGoogle Scholar
  19. [19]
    Liu J.W., Cai M.X., Xin Y., Wu Q.S., Ma J., Yang P., et al., Parthenolide induces proliferation inhibition and apoptosis of pancreatic cancer cells in vitro, J. Exp. Clin. Cancer Res., 2010, 29, 108PubMedCrossRefGoogle Scholar
  20. [20]
    Yang J., Liu X., Bhalla K., Kim C.N., Ibrado A.M., Cai J., et al., Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked, Science, 1997, 275, 1129–1132PubMedCrossRefGoogle Scholar
  21. [21]
    Lin X., Wang Y.J., Li Q., Hou Y.Y., Hong M.H., Cao Y.L., et al., Chronic high-dose morphine treatment promotes SH-SY5Y cell apoptosis via c-Jun N-terminal kinase-mediated activation of mitochondria-dependent pathway, FEBS J., 2009, 276, 2022–2036PubMedCrossRefGoogle Scholar
  22. [22]
    Tegeder I., Grösch S., Schmidtko A., Häussler A., Schmidt H., Niederberger E., et al., G proteinindependent G1 cell cycle block and apoptosis with morphine in adenocarcinoma cells: involvement of p53 phosphorylation, Cancer Res., 2003, 63, 1846–1852PubMedGoogle Scholar

Copyright information

© © Versita Warsaw and Springer-Verlag Wien 2012

Authors and Affiliations

  • Katarzyna Gach
    • 1
  • Anna Wyrębska
    • 1
  • Janusz Szemraj
    • 2
  • Anna Janecka
    • 1
    Email author
  1. 1.Department of Biomolecular ChemistryMedical University of LodzLodzPoland
  2. 2.Department of BiochemistryMedical University of LodzLodzPoland

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