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Inhibitory Effect of Retinoids on Alkaline Phosphatase Isoenzymes Activity in Human Serum

  • Kim, Seung Hee (Department of Dental Hygiene, Gwangju Health University) ;
  • Moon, Ki-Young (Department of Clinical Pathology, Gwangju Health University)
  • Received : 2017.08.08
  • Accepted : 2017.08.28
  • Published : 2017.09.30

Abstract

Changes in the activity of alkaline phosphatase (ALP) isoenzymes and isoforms in human serum have a major diagnostic value, therefore the regulation of ALP activities is a valuable target for therapeutic interventions. To assess the pharmacological activity of retinoids, i.e., all-trans retinoic acid and 13-cis retinoic acid, their tissue-specific inhibitory effect on human serum ALP activity was elucidated by chemical inhibition methods, heat-sensitive inactivation, and wheat-germ lectin precipitation test. Retinoids showed significant inhibition of the total ALP activity in human serum at a concentration of 5 mM. All-trans retinoic acid (5 mM) and 13-cis retinoic acid (5 mM) inhibited ALP activities by up to 12% and 15%, respectively, compared to that by guanidine hydrochloride (200 mM). L-phenylalanine (100 mM) and urea (30 mM) had no further inhibitory effect on ALP activities in human serum pretreated with retinoids (5 mM). Retinoids significantly inhibited ALP activities by up to 20% compared with that of tetramisole (30 mM). The ALP activities in retinoid-pretreated serum remained unchanged after the heat inactivation process. These results suggest that retinoids are inhibitors of the intestinal ALP isoenzyme. Remarkably, retinoids revealed potent inhibitory activities against ALP in wheat-germ lectin precipitant serum, indicating that they also function as inhibitors of the bone ALP isoform. The results show that retinoids inhibit the specific tissue-derived human serum ALP activities, moreover, the inhibitory effect of retinoids against bone ALP activity suggests their clinical utility as monitoring and prevention of metastasis of bone cancer.

Keywords

References

  1. Altucci L, Gronemeyer H. The promise of retinoids to fight against cancer. Nature Reviews Cancer. 2001. 1: 181-193. https://doi.org/10.1038/35106036
  2. Bahr M, Wilkinson JH. Urea as a selective inhibitor of human tissue alkaline phosphatase. Clinica Chimica Acta. 1967. 17:367-370. https://doi.org/10.1016/0009-8981(67)90211-2
  3. Balmer JE, Blomhoff R. Gene expression regulation by retinoic acid. Journal of Lipid Research. 2002. 43: 1773-1808. https://doi.org/10.1194/jlr.R100015-JLR200
  4. Behr W, Barnert J. Quantification of bone alkaline phosphatase in serum by precipitation with wheat-germ lectin: a simplified method and its clinical plausibility. Clinical Chemistry. 1986. 32: 1960-1966.
  5. Burlina A, Plebani M, Secchiero S, Zaninotto M, Sciacovelli L. Precipitation method for separating and quantifying bone and liver alkaline phosphatase isoenzymes. Clinical Biochemistry. 1991. 24: 417-423. https://doi.org/10.1016/S0009-9120(05)80017-7
  6. Burlina A, Rubin D, Secchiero S, Sciacovelli L, Zaninotto M, Plebani M. Monitoring skeletal cancer metastases with the bone isoenzyme of tissue unspecific alkaline phosphatase. Clinica Chimica Acta. 1994. 226: 151-158. https://doi.org/10.1016/0009-8981(94)90212-7
  7. Carratu MR, Marasco C, Mangialardi G, Vacca A. Retinoids: novel immunomodulators and tumour-suppressive agents? British Journal of Pharmacology. 2012. 167: 483-492. https://doi.org/10.1111/j.1476-5381.2012.02031.x
  8. Crofton PM. Biochemistry of alkaline phosphatase isoenzymes. Critical Reviews in Clinical Laboratory Sciences. 1982. 16:161-194. https://doi.org/10.3109/10408368209107027
  9. Darwiche N, Bazzi H, El-Touni L, Abou-Lteif G, Doueiri R, Hatoum A, Maalouf S, Gali-Muhtasib H. Regulation of ultraviolet B radiation-mediated activation of AP1 signaling by retinoids in primary keratinocytes. Radiation Research. 2005. 163: 296-306. https://doi.org/10.1667/RR3318
  10. Dent CE, Norris TSM, Smith R, Sutton RAL, Temperley JM. Steatorrhea with striking increase of plasma alkaline phosphatase of intestinal origin. Lancet. 1968. 1: 1333-1336.
  11. Epstein E, Kiechle FL, Artiss JD, Zak B. The clinical use of alkaline phosphatase enzymes. Clinics in Laboratory Medicine. 1986. 6: 491-505.
  12. Ertesvag A, Naderi S, Blomhoff HK. Regulation of B cell proliferation and differentiation by retinoic acid. Seminars in Immunology. 2009. 21: 36-41. https://doi.org/10.1016/j.smim.2008.06.005
  13. Fishman WH, Sie HG. Organ-specific inhibition of human alkaline phosphatase isoenzymes of liver, bone, intestine and placenta: L-phenylalanine, L-tryptophan and L-homoarginine. Enzymologia. 1971. 41: 141-167.
  14. Freemantle SJ, Spinella MJ, Dmitrovsky E. Retinoids in cancer therapy and chemoprevention: promise meets resistance. Oncogene. 2003. 22: 7305-7315. https://doi.org/10.1038/sj.onc.1206936
  15. Lippman SM, Kessler JF, Meyskens FL Jr. Retinoids as preventive and therapeutic anticancer agents (Part I). Cancer Treatment Reports. 1987. 71: 391-405.
  16. Lippman SM, Meyskens FL Jr. Treatment of advanced squamous cell carcinoma of the skin with isotretinoin. Annals of Internal Medicine. 1987. 107: 499-502. https://doi.org/10.7326/0003-4819-107-4-499
  17. Lotan R. Retinoids in cancer chemoprevention. FASEB Journal. 1996. 10: 1031-1039. https://doi.org/10.1096/fasebj.10.9.8801164
  18. Moon KY. The chemopreventive effect of retinoids on cellular NF-${\kappa}B$ activity induced by NMU and NEU in human malignant keratinocytes. Cancer Research and Treatment. 2007. 39:82-87. https://doi.org/10.4143/crt.2007.39.2.82
  19. Moon KY. Acrolein, an I-${\kappa}B{\alpha}$-independent downregulation of NF-${\kappa}B$ activity, causes the decrease in nitric oxide production in human malignant keratinocytes. Archives of Toxicology. 2011. 85: 499-504. https://doi.org/10.1007/s00204-010-0599-4
  20. Moss DW. Alkaline phosphatase isoenzymes. Clinical Chemistry. 1982. 28: 2007-2016.
  21. Neale FC, Clubb JS, Hotchkis D, Posen S. Heat stability of human placental alkaline phosphatase. Journal of Clinical Pathology. 1965. 18: 359-365. https://doi.org/10.1136/jcp.18.3.359
  22. Okuno M, Kojima S, Matsushima-Nishiwaki R, Tsurumi H, Muto Y, Friedman SL, Moriwaki H. Retinoids in cancer chemoprevention. Current Cancer Drug Targets. 2004. 4: 285-298. https://doi.org/10.2174/1568009043333023
  23. Paillaud E, Costa S, Fages C, Plassat JL, Rochette-Egly C, Monville C, Tardy M. Retinoic acid increases proliferation rate of GL-15 glioma cells, involving activation of STAT-3 transcription factor. Journal of Neuroscience Research. 2002. 67: 670-679. https://doi.org/10.1002/jnr.10110
  24. Rosalki SB. Bone-origin alkaline phosphatase in plasma by wheatgerm lectin methods in bone disease. Clinica Chimica Acta. 1994. 226: 143-150. https://doi.org/10.1016/0009-8981(94)90211-9
  25. Rosalki SB, Foo AY. Two new methods for separating and quantifying bone and liver alkaline phosphatase isoenzymes in plasma. Clinical Chemistry. 1984. 30: 1182-1186.
  26. Seargeant LE, Stinson RA. Evidence that three structural genes code for human alkaline phosphatases. Nature. 1979. 281: 152-154. https://doi.org/10.1038/281152a0
  27. Shephard MDS, Peake MJ. Quantitative method for the determination of serum alkaline phosphatase isoenzyme activity I. Guanidine hydrochloride: a new reagent for selectively inhibiting the major serum isoenzymes of alkaline phosphatase. Journal of Clinical Pathology. 1986. 39: 1025-1030. https://doi.org/10.1136/jcp.39.9.1025
  28. Shephard MDS, Peake MJ, Walmsley RN. Quantitative method for determining serum alkaline phosphatase isoenzyme activity II. Development and clinical application of method for measuring four serum alkaline phosphatase isoenzymes. Journal of Clinical Pathology. 1986. 39: 1031-1038. https://doi.org/10.1136/jcp.39.9.1031
  29. Stolbach LL, Krant MJ, Inglis NR, Fishman WH. Correlation of serum L-phenylalanine-sensitive alkaline phosphatase derived from intestine with ABO blood group of cirrhotics. Gastroenterology. 1967. 52: 819-827.
  30. Sorensen S. Wheat-germ agglutinin method for measuring bone and liver isoenzymes of alkaline phosphatase assessed on postmenopausal osteoporosis. Clinical Chemistry. 1988. 34:1636-1640.
  31. Van Belle H, De Broe ME, Wieme RJ. L-p-Bromotetramisole, a new reagent for use in measuring placental or intestinal isoenzymes of alkaline phosphatase in human serum. Clinical Chemistry. 1977. 23: 454-459.
  32. Walker AW. Intestinal alkaline phosphatase in serum of patients on maintenance haemodialysis. Clinica Chimica Acta. 1974. 55: 399-405. https://doi.org/10.1016/0009-8981(74)90015-1
  33. Zaninotto M, Secchiero S, Rubin D, Sciacovelli L, Trovo M, Bortolus R, Plebani M. Serum bone alkaline phosphatase in the follow-up of skeletal metastases. Anticancer Research. 1995. 15: 2223-2228.