Morphine and cancer progression: Hydrogen peroxide points to need for more research

Herbert Bosshart, MD

doi:10.5055/jom.2011.0051

Authors

Herbert Bosshart, MD

DOI:

https://doi.org/10.5055/jom.2011.0051

Keywords:

morphine, hydrogen peroxide, tumor growth

Abstract

Background: Morphine is widely used in the management of intractable cancer pain. However, conflicting views exist on two suspected nonanalgesic properties of morphine: suppression of immune function and inhibition of cancer progression.
Methods: In vitro measurement of the tumor growth-inhibiting signaling molecule, hydrogen peroxide (H2O2), released from the cultured acute monocytic leukemia cell line, THP-1, in the presence or absence of morphine.
Results: Morphine at concentrations of 10−8 M significantly reduced H2O2 release from THP-1 cells.
Conclusions: These results provide a proof of concept for morphine’s ability to inhibit H2O2 production and release in a leukemia cell system and point to a possible and as yet unrecognized tumor-promoting effect of morphine. More research is needed to systematically examine this suspected morphine-associated tumor-promoting effect.

Author Biography

Herbert Bosshart, MD

ARUD , Zurich, Switzerland.

References

Johnsen AT, Tholstrup D, Petersen MA, et al.: Health related quality of life in a nationally representative sample of haematological patients. Eur J Haematol. 2009; 83(2): 139-148.

Niscola P, Arcuri E, Giovannini M, et al.: Pain syndromes in haematological malignancies: An overview. Hematol J. 2004; 5(4): 293-303.

Spielberger R, Stiff P, Bensinger W, et al.: Palifermin for oral mucositis after intensive therapy for hematologic cancers. N Engl J Med. 2004; 351(25): 2590-2598.

Maneckjee R, Biswas R, Vonderhaar BK: Binding of opioids to human MCF-7 breast cancer cells and their effects on growth. Cancer Res. 1990; 50(8): 2234-2238.

Maneckjee R, Minna JD: Nonconventional opioid binding sites mediate growth inhibitory effects of methadone on human lung cancer cells. Proc Natl Acad Sci USA. 1992; 89(4): 1169-1173.

Maneckjee R, Minna JD: Opioids induce while nicotine suppresses apoptosis in human lung cancer cells. Cell Growth Differ. 1994; 5(10): 1033-1040.

Hatzoglou A, L'Houcine O, Bakogeorgou K, et al.: Morphine cross-reacts with somatostatin receptor SSTR2 in the T47D human breast cancer cell line and decreases cell growth. Cancer Res. 1995; 55(23): 5632-5636.

Gupta K, Kshirsagar S, Chang L, et al.: Morphine stimulates angiogenesis by activating proangiogenic and survival-promoting signaling and promotes breast tumor growth. Cancer Res. 2002; 62(15): 4491-4498.

Tegeder I, Grösch S, Schmidtko A, et al.: G protein-independent G1 cell cycle block and apoptosis with morphine in adenocarcinoma cells: Involvement of p53 phosphorylation. Cancer Res. 2003; 63(8): 1846-1852.

Nathan CF, Brukner LH, Silverstein SC, et al.: Extracellular cytolysis by activated macrophages and granulocytes. I. Pharmacologic triggering of effector cells and the release of hydrogen peroxide. J Exp Med. 1979; 149(1): 100-113.

Nathan CF, Silverstein SC, Brukner LH, et al.: Extracellular cytolysis by activated macrophages and granulocytes. II. Hydrogen peroxide as a mediator of cytotoxicity. J Exp Med. 1979; 149(1): 84-99.

Westman NG, Marklund SL: Copper-and zinc-containing superoxide dismutase and manganese-containing superoxide dismutase in human tissues and human malignant tumors. Cancer Res. 1981; 41(7): 2962-2966.

Jing Y, Dai J, Chalmers-Redman RM, et al.: Arsenic trioxide selectively induces acute promyelocytic leukemia cell apoptosis via a hydrogen peroxide-dependent pathway. Blood. 1999; 94(6): 2102-2111.

Wagner BA, Buettner GR, Oberley LW, et al.: Myeloperoxidase is involved in H2O2-induced apoptosis of HL-60 human leukemia cells. J Biol Chem. 2000; 275(29): 22461-22469.

Kinnula VL, Crapo JD: Superoxide dismutase in malignant cells and human tumors. Free Radic Biol Med. 2004; 36(6): 718-744.

Tsuchiya S, Yamabe M, Yamaguchi Y, et al.: Establishment and characterization of a human acute monocytic leukemia cell line (THP-1). Int J Cancer. 1980; 26(2): 171-176.

Schiff DE, Kline L, Soldau K, et al.: Phagocytosis of gramnegative bacteria by a unique CD14-dependent mechanism. J Leukoc Biol. 1997; 62(6): 786-794.

Reid TM, Loeb LA: Mutagenic specificity of oxygen radicals produced by human leukemia cells. Cancer Res. 1992; 52(5): 1082-1086.

Pugin J, Kravchenko VV, Lee JD, et al.: Cell activation mediated by glycosylphosphatidylinositol-anchored or transmembrane forms of CD14. Infect Immun. 1998; 66(3): 1174-1180.

Mohanty JG, Jaffe JS, Schulman ES, et al.: A highly sensitive fluorescent micro-assay of H2O2 release from activated human leukocytes using a dihydroxyphenoxazine derivative. J Immunol Methods. 1997; 202(2): 133-141.

Savina A, Amigorena S: Phagocytosis and antigen presentation in dendritic cells. Immunol Rev. 2007; 219: 143-156.

Hiraoka W, Vazquez N, Nieves-Neira W, et al.: Role of oxygen radicals generated by NADPH oxidase in apoptosis induced in human leukemia cells. J Clin Invest. 1998; 102(11): 1961-1968.

Sancho P, Troyano A, Fernandez C, et al.: Differential effects of catalase on apoptosis induction in human promonocytic cells. Relationships with heat-shock protein expression. Mol Pharmacol. 2003; 63(3): 581-589.

Yanagisawa-Shiota F, Sakagami H, Kuribayashi N, et al.: Endonuclease activity and induction of DNA fragmentation in human myelogenous leukemic cell lines. Anticancer Res. 1995; 15(2): 259-265.