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Published in:

01-08-2011 | Review Article

Possible link between cyclooxygenase-inhibiting and antitumor properties of propofol

Authors: Takefumi Inada, Kozue Kubo, Koh Shingu

Published in: Journal of Anesthesia | Issue 4/2011

Abstract

The intravenous anesthetic propofol has a number of well-known nonanesthetic effects, including anti-oxidation and anti-emesis. Another interesting nonanesthetic effect of propofol may be its cyclooxygenase (COX)-inhibiting activity. This activity may have important clinical implications, as propofol could have antitumor properties through COX inhibition. Propofol could counteract the activity of COX, which elicits, via its major product prostaglandin E₂, (1) tumor growth stimulation, (2) increased tumor survival, (3) enhanced tumor invasiveness, (4) stimulation of new vessel formation, and (5) tumor evasion of host immune surveillance through suppression of immune cell functions. Indeed, accumulated evidence indicates that propofol suppresses the proliferation, motility, and invasiveness of tumors in vitro and in vivo. Therefore, propofol could be a particularly suitable anesthetic for use during the perioperative period for cancer surgery. However, whether the COX-inhibiting activity of propofol is related to the reported antitumor properties of propofol is not known. Definitive evidence remains to be provided.

Needleman P, Turk J, Jakschik BA, Morrison AR, Lefkowith JB. Arachidonic acid metabolism. Annu Rev Biochem. 1986;55:69–102.PubMedCrossRef

Jones DA, Carlton DP, McIntyre TM, Zimmerman GA, Prescott SM. Molecular cloning of human prostaglandin endoperoxide synthase type II and demonstration of expression in response to cytokines. J Biol Chem. 1993;268:9049–54.PubMed

Vasileiou I, Xanthos T, Koudouna E, Perrea D, Klonaris C, Katsargyris A, Papadimitriou L. Propofol: a review of its non-anaesthetic effects. Eur J Pharmacol. 2009;605:1–8.PubMedCrossRef

Rizzo MT. Cyclooxygenase-2 in oncogenesis. Clin Chim Acta. 2011;412:671–87.PubMedCrossRef

Pozzi A, Yan X, Macias-Perez I, Wei S, Hata AN, Breyer RM, Morrow JD, Capdevila JH. Colon carcinoma cell growth is associated with prostaglandin E2/EP4 receptor-evoked ERK activation. J Biol Chem. 2004;279:29797–804.PubMedCrossRef

Sheng H, Shao J, Morrow JD, Beauchamp RD, DuBois RN. Modulation of apoptosis and Bcl-2 expression by prostaglandin E2 in human colon cancer cells. Cancer Res. 1998;58:362–6.PubMed

Greenhough A, Wallam CA, Hicks DJ, Moorghen M, Williams AC, Paraskeva C. The proapoptotic BH3-only protein Bim is downregulated in a subset of colorectal cancers and is repressed by antiapoptotic COX-2/PGE(2) signalling in colorectal adenoma cells. Oncogene. 2010;29:3398–410.PubMedCrossRef

Krysan K, Dalwadi H, Sharma S, Pold M, Dubinett S. Cyclooxygenase 2-dependent expression of survivin is critical for apoptosis resistance in non-small cell lung cancer. Cancer Res. 2004;64:6359–62.PubMedCrossRef

Yen JH, Khayrullina T, Ganea D. PGE₂-induced metalloproteinase-9 is essential for dendritic cell migration. Blood. 2008;111:260–70.PubMedCrossRef

10.

Jain S, Chakraborty G, Raja R, Kale S, Kundu GC. Prostaglandin E₂ regulates tumor angiogenesis in prostate cancer. Cancer Res. 2008;68:7750–9.PubMedCrossRef

11.

Richardsen E, Uglehus RD, Due J, Busch C, Busund LT. COX-2 is overexpressed in primary prostate cancer with metastatic potential and may predict survival. A comparison study between COX-2, TGF-beta, IL-10 and Ki67. Cancer Epidemiol. 2010;34:316–22.PubMedCrossRef

12.

Denkert C, Winzer KJ, Muller BM, Weichert W, Pest S, Kobel M, Kristiansen G, Reles A, Siegert A, Guski H, Hauptmann S. Elevated expression of cyclooxygenase-2 is a negative prognostic factor for disease free survival and overall survival in patients with breast carcinoma. Cancer (Phila). 2003;97:2978–87.CrossRef

13.

Bocca C, Bozzo F, Bassignana A, Miglietta A. Antiproliferative effects of COX-2 inhibitor celecoxib on human breast cancer cell lines. Mol Cell Biochem. 2011;350:59–70.PubMedCrossRef

14.

Mantovani G, Maccio A, Madeddu C, Serpe R, Antoni G, Massa E, Dessl M, Panzone F. Phase II nonrandomized study of the efficacy and safety of COX-2 inhibitor celecoxib on patients with cancer cachexia. J Mol Med. 2010;88:85–92.PubMedCrossRef

15.

Elmets CA, Viner JL, Pentland AP, Cantrell W, Lin HY, Bailey H, Kang S, Linden KG, Heffeman M, Duvic M, Richmond E. Chemoprevention of nonmelanoma skin cancer with celecoxib: a randomized, double-blind, placebo-controlled trial. J Natl Cancer Inst. 2010;102:1835–44.PubMedCrossRef

16.

Rothwell PM, Fowkes FG, Belch JF, Ogawa H, Warlow CP, Meade TW. Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials. Lancet. 2011;377:31–41.PubMedCrossRef

17.

Baxevanis CN, Reclos GJ, Gritzapis AD, Dedousis GV, Missitzis I, Papamichail M. Elevated prostaglandin E₂ production by monocytes is responsible for the depressed levels of natural killer and lymphokine-activated killer cell function in patients with breast cancer. Cancer (Phila). 1993;72:491–501.CrossRef

18.

Harizi H, Juzan M, Pitard V, Moreau JF, Gualde N. Cyclooxygenase-2-issued prostaglandin E₂ enhances the production of endogenous IL-10, which down-regulates dendritic cell functions. J Immunol. 2002;168:2255–63.PubMed

19.

Sharma S, Yang SC, Zhu L, Reckamp K, Gardner B, Baratelli F, Huang M, Batra RK, Dubinett SM. Tumor cyclooxygenase-2/prostaglandin E2-dependent promotion of FOXP3 expression and CD4+ CD25+ T regulatory cell activities in lung cancer. Cancer Res. 2005;65:5211–20.PubMedCrossRef

20.

Eruslanov E, Daurkin I, Ortiz J, Vieweg J, Kusmartsev S. Tumor-mediated induction of myeloid-derived suppressor cells and M2-polarized macrophages by altering intracellular PGE(2) catabolism in myeloid cells. J Leukoc Biol. 2010;88:839–48.PubMedCrossRef

21.

Sinha P, Clements VK, Fulton AM, Ostrand-Rosenberg S. Prostaglandin E₂ promotes tumor progression by inducing myeloid-derived suppressor cells. Cancer Res. 2007;67:4507–13.PubMedCrossRef

22.

Ono M. Molecular links between tumor angiogenesis and inflammation: inflammatory stimuli of macrophages and cancer cells as targets for therapeutic strategy. Cancer Sci. 2008;99:1501–6.PubMedCrossRef

23.

Midgley RS, McConkey CC, Johnstone EC, Dunn JA, Smith JL, Grumett SA, Julier P, Iveson C, Yanagisawa Y, Warren B, Langman MJ, Kerr DJ. Phase III randomized trial assessing rofecoxib in the adjuvant setting of colorectal cancer: final results of the VICTOR trial. J Clin Oncol. 2010;28:4575–80.PubMedCrossRef

24.

Inada T, Kubo K, Kambara T, Shingu K. Propofol inhibits cyclo-oxygenase activity in human monocytic THP-1 cells. Can J Anaesth. 2009;56:222–9.PubMedCrossRef

25.

Kambara T, Inada T, Kubo K, Shingu K. Propofol suppresses prostaglandin E(2) production in human peripheral monocytes. Immunopharmacol Immunotoxicol. 2009;31:117–26.PubMedCrossRef

26.

Inada T, Kubo K, Shingu K. Promotion of interferon-gamma production by natural killer cells via suppression of murine peritoneal macrophage prostaglandin E₂ production using intravenous anesthetic propofol. Int Immunopharmacol. 2010;10:1200–8.PubMedCrossRef

27.

Furukawa K, Yamamori H, Takagi K, Hayashi N, Suzuki R, Nakajima N, Tashiro T. Influences of soybean oil emulsion on stress response and cell-mediated immune function in moderately or severely stressed patients. Nutrition. 2002;18:235–40.PubMedCrossRef

28.

Matsuura M, Saito S, Hirai Y, Okamura H. A pathway through interferon-gamma is the main pathway for induction of nitric oxide upon stimulation with bacterial lipopolysaccharide in mouse peritoneal cells. Eur J Biochem. 2003;270:4016–25.PubMedCrossRef

29.

Sica A, Porta C. Role of tumor-associated macrophages (TAM) in cancer related inflammation. In: Siemann DW, editor. Tumor microenvironment. West Sussex: Wiley; 2011. p. 77–98.

30.

Elgert KD, Alleva DG, Mullins DW. Tumor-induced immune dysfunction: the macrophage connection. J Leukoc Biol. 1998;64:275–90.PubMed

31.

Tsuchiya M, Asada A, Arita K, Utsumi T, Yoshida T, Sato EF, Utsumi K, Inoue M. Induction and mechanism of apoptotic cell death by propofol in HL-60 cells. Acta Anaesthesiol Scand. 2002;46:1068–74.PubMedCrossRef

32.

Miao YF, Zhang YW, Wan HJ, Chen LB, Wang FY. GABA-receptor agonist, propofol inhibits invasion of colon carcinoma cells. Biomed Pharmacother. 2010;64:583–8.PubMedCrossRef

33.

Mammoto T, Mukai M, Mammoto A, Yamanaka Y, Hayashi Y, Mashimo T, Kishi Y, Nakamura H. Intravenous anesthetic, propofol inhibits invasion of cancer cells. Cancer Lett. 2002;184:165–70.PubMedCrossRef

34.

Sompayrac L. Cancer and the immune system. In: Sompayrac L, editor. How the immune system works. Boston: Blackwell; 2003. p. 109–16.

35.

Melamed R, Bar-Yosef S, Shakhar G, Shakhar K, Ben-Eliyahu S. Suppression of natural killer cell activity and promotion of tumor metastasis by ketamine, thiopental, and halothane, but not by propofol: mediating mechanisms and prophylactic measures. Anesth Analg. 2003;97:1331–9.PubMedCrossRef

36.

Hashimoto H, Araki I, Sato T, Matsuki A. Clinical study on total intravenous anesthesia with droperidol, fentanyl and ketamine-7. Effects on natural killer cell activity. Masui (Jpn J Anesthesiol). 1991;40:912–7. (in Japanese with English abstract).

37.

Kushida A, Inada T, Shingu K. Enhancement of antitumor immunity after propofol treatment in mice. Immunopharmacol Immunotoxicol. 2007;29:477–86.PubMedCrossRef

38.

Inada T, Kubo K, Shingu K. Vaccines using dendritic cells, differentiated with propofol, enhance antitumor immunity in mice. Immunopharmacol Immunotoxicol. 2009;31:150–7.PubMedCrossRef

39.

Salem ML. Systemic treatment with n-6 polyunsaturated fatty acids attenuates EL4 thymoma growth and metastasis through enhancing specific and non-specific anti-tumor cytolytic activities and production of TH1 cytokines. Int Immunopharmacol. 2005;5:947–60.PubMedCrossRef

40.

Kaizer L, Boyd NF, Kriukov V, Tritchler D. Fish consumption and breast cancer risk: an ecological study. Nutr Cancer. 1989;12:61–8.PubMedCrossRef

41.

Terry P, Lichtenstein P, Feychting M, Ahlbom A, Wolk A. Fatty fish consumption and risk of prostate cancer. Lancet. 2001;357:1764–6.PubMedCrossRef

42.

Siddiqui RA, Zerouga M, Wu M, Castillo A, Harvey K, Zaloga GP, Stillwell W. Anticancer properties of propofol-docosahexaenoate and propofol-eicosapentaenoate on breast cancer cells. Breast Cancer Res. 2005;7:R645–54.PubMedCrossRef

43.

Greenhough A, Smartt HJ, Moore AE, Roberts HR, Williams AC, Paraskeva C, Kaidi A. The COX-2/PGE2 pathway: key roles in the hallmarks of cancer and adaptation to the tumour microenvironment. Carcinogenesis (Oxf). 2009;30:377–86.CrossRef

44.

Yamaguchi K, Takagi Y, Aoki S, Futamura M, Saji S. Significant detection of circulating cancer cells in the blood by reverse transcriptase-polymerase chain reaction during colorectal cancer resection. Ann Surg. 2000;232:58–65.PubMedCrossRef

45.

Gupta GP, Massague J. Cancer metastasis: building a framework. Cell. 2006;127:679–95.PubMedCrossRef

46.

Brittenden J, Heys SD, Ross J, Eremin O. Natural killer cells and cancer. Cancer (Phila). 1996;77:1226–43.CrossRef

47.

Slade MS, Simmons RL, Yunis E, Greenberg LJ. Immunodepression after major surgery in normal patients. Surgery (St. Louis). 1975;78:363–72.

48.

Ogawa K, Hirai M, Katsube T, Murayama M, Hamaguchi K, Shimakawa T, Naritake Y, Hosokawa T, Kajiwara T. Suppression of cellular immunity by surgical stress. Surgery (St. Louis). 2000;127:329–36.CrossRef

49.

Weissman C. The metabolic response to stress: an overview and update. Anesthesiology. 1990;73:308–27.PubMedCrossRef

50.

Chrousos GP. The hypothalamic–pituitary–adrenal axis and immune-mediated inflammation. N Engl J Med. 1995;332:1351–62.PubMedCrossRef

51.

Shakhar G, Ben-Eliyahu S. In vivo beta-adrenergic stimulation suppresses natural killer activity and compromises resistance to tumor metastasis in rats. J Immunol. 1998;160:3251–8.PubMed

52.

Tsuchiya Y, Sawada S, Yoshioka I, Ohashi Y, Matsuo M, Harimaya Y, Tsukada K, Saiki I. Increased surgical stress promotes tumor metastasis. Surgery (St. Louis). 2003;133:547–55.CrossRef

53.

Elenkov IJ, Chrousos GP. Stress hormones, proinflammatory and antiinflammatory cytokines, and autoimmunity. Ann N Y Acad Sci. 2002;966:290–303.PubMedCrossRef

54.

Tartter PI, Steinberg B, Barron DM, Martinelli G. The prognostic significance of natural killer cytotoxicity in patients with colorectal cancer. Arch Surg. 1987;122:1264–8.PubMed

55.

Takeuchi H, Maehara Y, Tokunaga E, Koga T, Kakeji Y, Sugimachi K. Prognostic significance of natural killer cell activity in patients with gastric carcinoma: a multivariate analysis. Am J Gastroenterol. 2001;96:574–8.PubMedCrossRef

56.

Benish M, Bartal I, Goldfarb Y, Levi B, Avraham R, Raz A, Ben-Eliyahu S. Perioperative use of beta-blockers and COX-2 inhibitors may improve immune competence and reduce the risk of tumor metastasis. Ann Surg Oncol. 2008;15:2042–52.PubMedCrossRef

57.

Glasner A, Avraham R, Rosenne E, Benish M, Zmora O, Shemer S, Meiboon H, Ben-Eliyahu S. Improving survival rates in two models of spontaneous postoperative metastasis in mice by combined administration of a beta-adrenergic antagonist and a cyclooxygenase-2 inhibitor. J Immunol. 2010;184:2449–57.PubMedCrossRef

58.

Deegan CA, Murray D, Doran P, Ecimovic P, Moriarty DC, Buggy DJ. Effect of anaesthetic technique on oestrogen receptor-negative breast cancer cell function in vitro. Br J Anaesth. 2009;103:685–90.PubMedCrossRef

59.

Forget P, Collet V, Lavand’homme P, De Kock M. Does analgesia and condition influence immunity after surgery? Effects of fentanyl, ketamine and clonidine on natural killer activity at different ages. Eur J Anaesthesiol. 2010;27:233–40.PubMedCrossRef

60.

Pirttikangas CO, Salo M, Mansikka M, Gronroos J, Pulkki K, Peltola O. The influence of anaesthetic technique upon the immune response to hysterectomy. A comparison of propofol infusion and isoflurane. Anaesthesia. 1995;50:1056–61.PubMedCrossRef

61.

Ren XF, Li WZ, Meng FY, Lin CF. Differential effects of propofol and isoflurane on the activation of T-helper cells in lung cancer patients. Anaesthesia. 2010;65:478–82.PubMedCrossRef

62.

Inada T, Yamanouchi Y, Jomura S, Sakamoto S, Takahashi M, Kambara T, Shingu K. Effect of propofol and isoflurane anaesthesia on the immune response to surgery. Anaesthesia. 2004;59:954–9.PubMedCrossRef

Title: Possible link between cyclooxygenase-inhibiting and antitumor properties of propofol
Authors: Takefumi Inada
Kozue Kubo
Koh Shingu
Publication date: 01-08-2011
Publisher: Springer Japan
Published in: Journal of Anesthesia / Issue 4/2011
Print ISSN: 0913-8668
Electronic ISSN: 1438-8359
DOI: https://doi.org/10.1007/s00540-011-1163-y

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Possible link between cyclooxygenase-inhibiting and antitumor properties of propofol

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