Carnitine System and Tumor

  • Menotti Calvani
  • Raffaela Nicolai
  • Alfonso Barbarisi
  • Emilia Reda
  • Paola Benatti
  • Gianfranco Peluso
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 472)


Carnitine, a name derived from the Latin carnis (flesh), was isolated from meat extracts in 19051 and early its chemical formula (C7H15NO3) was proposed. Its structure, a trimethylbetaine of γ-amino-β-hydroxybutyric acid, was correctly identified and published about twenty years later.2 Initially, some circumstances led to consider carnitine as a vitamin. By about 1945, all of the important vitamins of the B group had been identified, but the interest in the discovery of still missing B-vitamins, their lack being possibly correlated with anemia, was tremendous. In those years Fraenkel and coworkers observed that the mealworm Tenebrio molitor required for normal growth and survival, in addition to at least eight of the known B-vitamins, also folic acid and a new factor contained in brewers yeast or in liver extract, which they tentatively named vitamin-BT (T for Tenebrio).3 The unfavorable properties of this factor (it was hygroscopic and extremely water soluble, thus, hard to crystallize) made its isolation difficult but, finally, the missing vitamin-BT was identified as carnitine.4 The widespread distribution of carnitine was established in microorganisms, lower animals, and in all organs of mammals, and in plants too.5


Fatty Acid Oxidation Free Carnitine Carnitine Ester Fatty Acid Turnover Carnitine Metabolism 
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  1. 1.
    Gulewitsh W. and Krimberg R. Zur Kenntnis der Extraktivstoffe der Muskeln. Z. Physiol. Chem. 45: 326–330, 1905.CrossRefGoogle Scholar
  2. 2.
    Tomita M. and Sendju Y. Uber die Oxyaminoverbindungen, welche die Biuretreaktion zeigen, Z. Physiol. Chem. 169: 263, 1927.Google Scholar
  3. 3.
    Fraenkel G., Blewett M., and Coles M. BT, a new vitamin of the B-group and its relation to the folic acid group, and other anti-anaemia factors. Nature 161 (4103): 981–983, 1948.PubMedCrossRefGoogle Scholar
  4. 4.
    Carter H.E., Bhattacharyya P.K., Weidman K.R., and Fraenkel G. Chemical studies on vitamin BT. Isolation and characterization as carnitine, Arch. Biochem. Biophys. 38: 405–416, 1952.CrossRefGoogle Scholar
  5. 5.
    Fraenkel G. and Friedman S. Carnitine. Vitam. Horm.15:73–118, 1957.Google Scholar
  6. 6.
    Lindstedt G. and Lindstedt S. On the biosynthesis and degradation of carnitine, Biochem. Biophys. Res. Commun. 6 (5): 319–323, 1961.CrossRefGoogle Scholar
  7. 7.
    Bremer J. Carnitine precursors in the rat, Biochim. Biophys. Acta 57:327–335, 1962.Google Scholar
  8. 8.
    Horne D.W., Tanphaichitr V., and Broquist H.P. Role of lysine in carnitine biosynthesis in Neurospora crassa, J. Biol. Chem. 246 (13): 4373–4375, 1971.PubMedGoogle Scholar
  9. 9.
    Jung H., Jung K., and Kleber H.P. L-carnitine metabolization and osmotic stress response in Escherichia coli, J. Basic Microbiol. 30 (6): 409–413, 1990.PubMedCrossRefGoogle Scholar
  10. 10.
    Rebouche C.J. and Seim H. Carnitine metabolism and its regulation in microorganisms and mammals, Annu. Rev. Nutr. 18:39–61, 1998.Google Scholar
  11. 11.
    Fritz I.B. The effect of muscle extracts on the oxidation of palmitic acid by liver slices and homogenates, Acta Physiol. Scand. 34: 367, 1955.Google Scholar
  12. 12.
    Neumann G. Effect of L-carnitine on athletic performance. In: Carnitine. Pathobiochemical Basics and Clin. Applications, pp. 61–71, 1996.Google Scholar
  13. 13.
    Lombard K.A., Olson A.L., Nelson S.E., and Rebouche C.J. Carnitine status of lactoovovegetarians and strict vegetarian adults and children, Am. J. Clin. Nutr. 50 (2): 301–306, 1989.PubMedGoogle Scholar
  14. 14.
    Novak M. The role and importance of L-carnitine in infants nutrition. International symposium on infant nutrition, Beijing, China, 21–23/9/1993.Google Scholar
  15. 15.
    Rebouche C.J. and Chenard C.A. Metabolic fate of dietary carnitine in human adults: identification and quantification of urinary and fecal metabolites, J. Nutr. 121 (4): 539–546, 1991.PubMedGoogle Scholar
  16. 16.
    Bulla M., Glöggler A., Rößle C., and Fürst P. Dysregulation of carnitine metabolism in renal insufficiency: a summary of findings in adults and children. In: Carnitine. Pathobiochemical Basics and Clin Applications. H. Seim and H Löster, editors; Ponte Press, pp. 177–194, 1996.Google Scholar
  17. 17.
    Rebouche C.J. and Engel A.G. Kinetic compartmental analysis of carnitine metabolism in the human carnitine deficiency syndromes. Evidence for alterations in tissue carnitine transport, J. Clin. Invest. 73 (3): 857–867, 1984.PubMedCrossRefGoogle Scholar
  18. 18.
    Brass E.P. Carnitine transport. In: L-Carnitine and its role in Medicine: from function to therapy. R. Ferrari, S. DiMauro, and G. Sherwood, editors; Academic Press, pp. 21–36,1992.Google Scholar
  19. 19.
    Scholte H.R., Boonman A.M.C., Hussaarts-Odijk L.M., Ross J.D., Van Oudheusden L.J., Rodrigues Pereira R., and Wallenburg H.C.S. New aspects of the biochemical regulation of the carnitine system and mitochondrial fatty acid oxidation. In: Carnitine. Pathobiochemical basics and clinical applications. Seim H. and Löster H. editors, Ponte Press Verlags-GmbH, pp. 11–34, 1996.Google Scholar
  20. 20.
    Rebouche C.J., Lehman L.J., and Olson L. Epsilon-N-trimethyllysine availability regulates the rate of carnitine biosynthesis in the growing rat, J. Nutr. 116 (5): 751–759, 1986.PubMedGoogle Scholar
  21. 21.
    Tamai I. Ohashi R., Nezu J., Yabuuchi H., Oku A., Shimane M., Sai Y., and Tsuji A. Molecular and functional identification of sodium ion-dependent, high affinity human carnitine transporter OCTN2, J. Biol. Chem. 273(32):20378–20382, 1998.Google Scholar
  22. 22.
    Hoppel C. The physiological role of carnitine. In: L-Carnitine and its role in medicine: From function to therapy. Ferrari R, DiMauro S, and Sherwood G editors; Academic Press Limited, pp. 5–19, 1992.Google Scholar
  23. 23.
    Bremer J. The role of carnitine in cell metabolism. In: Carnitine Today, C. de Simone and G. Famularo, editors; Springer-Verlag, Heidelberg, pp. 1–37, 1997.Google Scholar
  24. 24.
    McGarry J.D. and Brown N.E. The mitochondrial carnitine palmitoyltransferase system. From concept to molecular analysis, Eur. J. Biochem. 244 (1): 1–14, 1997.PubMedCrossRefGoogle Scholar
  25. 25.
    Murthy M.S.R. and Pande S.V. Malonyl-CoA binding site and the overt carnitine palmitoyltransferase activity reside on the opposite sides of the outer mitochondrial membrane, Proc.Natl. Acad. Sci. USA 84 (2): 378–382, 1987.PubMedCrossRefGoogle Scholar
  26. 26.
    Declercq P.E., Falck J.R., Kuwajima M., Tyminski H., Foster D.W., and McGarry J.D. Characterization of the mitochondrial carnitine palmitoyltransferase enzyme system. I. Use of inhibitors, J. Biol. Chem. 262 (20): 9812–9821, 1987.Google Scholar
  27. 27.
    Woeltje K.F., Kuwajima M., Foster D.W., and McGarry J.D. Characterization of the mitochondrial carnitine palmitoyltransferase enzyme system. II. Use of detergents and antibodies, J. Biol. Chem. 262: 9822–9827, 1987.PubMedGoogle Scholar
  28. 28.
    Pande S.V. A mitochondrial carnitine acylcarnitine translocase system, Proc. Natl. Acad. Sci. USA 72 (3): 883–887, 1975.PubMedCrossRefGoogle Scholar
  29. 29.
    Indiveri C., Tonazzi A, and Palmieri F. Identification and purification of carnitine carrier from rat liver mitochondria, Biochi. Biophys. Acta 1020 (1): 81–86, 1990.CrossRefGoogle Scholar
  30. 30.
    Indiveri C., Tonazzi A., and Palmieri E. Characterization of the unidirectional transport of carnitine catalized by the reconstituted carnitine carrier from rat liver mitochondria, Biochim. Biophys Acta 1069 (1): 110–116, 1991.CrossRefGoogle Scholar
  31. 31.
    Noël H. and Pande S.V. An essential requirement of cardiolipin for mitochondrial carnitine acylcarnitine translocase activity. Lipid requirement of carnitine acylcarnitine translocase, Eur. J. Biochem. 155 (1): 99–102, 1986.PubMedCrossRefGoogle Scholar
  32. 32.
    Edwards Y.H., Chase J.F.A., Edwards M.R., and Tubbs P.K. Carnitine acetyltransferase: the question of multiple forms, Eur. J. Biochem. 46 (1): 209–215, 1974.PubMedCrossRefGoogle Scholar
  33. 33.
    Bremer J. Carnitine Metabolism and functions, Physiol. Rev. 63(4):1420–1480,1983.Google Scholar
  34. 34.
    Bieber L.L. Carnitine. Annu. Rev. Biochem. 57:261–283, 1988.Google Scholar
  35. 35.
    Murthy M.S.R. and Pande S.V. Characterization of a solubilized malonyl-CoA sensitive carnitine palmitoyltransferase from the mitochondrial outer membrane as a protein distinct from the malonylCoA insensitive enzyme of the inner membrane. Biochem. J. 268 (3): 599–604, 1990.PubMedGoogle Scholar
  36. 36.
    Murthy M.S.R. and Pande S.V. Molecular biology of carnitine palmitoyltransferases and role of carnitine in gene transcription, In: Carnitine Today, C. de Simone and G. Famularo, editors; Springer-Verlag, Heidelberg, pp. 39–70, 1997.Google Scholar
  37. 37.
    Buechler K.F. and Lowenstein J.M. The involvement of carnitine intermediates in peroxisomal fatty acid oxidation: a study with 2-bromofatty acids, Arch. Biochem. Biophys. 281 (2): 233–238, 1990.CrossRefGoogle Scholar
  38. 38.
    Jakobs B.S. and Wanders R.J. Fatty acid beta-oxidation in peroxisomes and mitochondria: the first, unequivocal evidence for the involvement of carnitine in shuttling propionyl-CoA from peroxisomes to mitochondria, Biochem. Biophys. Res. Commun. 213 (3): 1035–1041, 1995.CrossRefGoogle Scholar
  39. 39.
    Solberg H.E. and Bremer J. Formation of branched chain acylcarnitines in mitochondria, Biochim. Biophys. Acta 222 (2): 372–380, 1970.CrossRefGoogle Scholar
  40. 40.
    Singh H., Beckman K., and Poulos A. Peroxisomal beta-oxidation of branched chain fatty acids in rat liver. Evidence that carnitine palmitoyltransferase I prevents transport of branched chain fatty acids into mitochondria, J. Biol. Chem. 269 (13): 9514–9520, 1994.PubMedGoogle Scholar
  41. 41.
    Lysiak W, Lilly K., Di Lisa E, Toth P.P., and Bieber L.L. Quantitation of the effect of L-carnitine on the levels of acid-soluble short-chain acyl-Coa and CoASH in rat heart and liver mitochondria, J. Biol. Chem. 263 (3): 1151–1156, 1988.PubMedGoogle Scholar
  42. 42.
    Diep Q.N. and Bohmer T. Increased pivaloylcarnitine in the liver of the sodium pivalate treated rat exposed to clofibrate, Biochim. Biophys. Acta 1256 (2): 245–247, 1995.CrossRefGoogle Scholar
  43. 43.
    Wittels B. and Hochstein P. The identification of carnitine palmityltransferase in erythrocyte membranes, J. Biol. Chem. 242 (1): 126–130, 1967.PubMedGoogle Scholar
  44. 44.
    Ramsay R.R., Mancinelli G., and Arduini A. Carnitine palmitoyltransferase in human erythrocyte membrane. Properties and malonyl-CoA sensitivity, Biochem. J. 275 (Pt3): 685–688, 1991.Google Scholar
  45. 45.
    Arduini A., Mancinelli G., Radatti G.L., Dottori S., Molajoni E, and Ramsay R.R. Role of carnitine and carnitine palmitoyltransferase as integral components of the pathway for membrane phospholipid fatty acid turnover in intact human erythrocytes, J. Biol. Chem. 267 (18): 12673–12681, 1992.PubMedGoogle Scholar
  46. 46.
    Arduini A., Denisova N., Virmani A., Avrova N., Federici G., and Arrigoni Martelli E. Evidence for the involvement of carnitine-dependent long-chain acyltransferases in neuronal triglyceride and phospholipid fatty acid turnover, J. Neurochem. 62 (4): 1530–1538, 1994.PubMedCrossRefGoogle Scholar
  47. 47.
    Broadway N.M. and Saggerson E.D. Microsomal carnitine acyltransferases. Biochem. Soc. Trans. 23 (3): 490–494, 1995.PubMedGoogle Scholar
  48. 48.
    Tomaszewski K.E. and Melnick R.L. In vitro evidence for involvement of CoA thioesters in peroxisome proliferation and hypolipidaemia, Biochim. Biophys. Acta 1220 (2): 118–124, 1994.PubMedCrossRefGoogle Scholar
  49. 49.
    Nishimaki-Mogami T., Takahashi A., and Hayashi Y. Activation of a peroxisome-proliferating catabolite of cholic acid to its CoA ester, Biochem. J. 296 (Pt 1): 265–270, 1993.PubMedGoogle Scholar
  50. 50.
    Fujibayashi Y., Waki A., Sakahara H., Konishi J., Yonekura Y., Ishii Y., and Yokoyama A. Transient increase in glycolytic metabolism in cultured tumor cells immediately after exposure to ionizing radiation: from gene expression to deoxyglucose uptake, Radiat. Res. 147 (6): 729–734, 1997.Google Scholar
  51. 51.
    Rodriguez-Enriquez S. and Moreno-Sanchez R. Intermediary metabolism of fast-growth tumor cells, Arch. Med. Res. 29 (1): 1–12, 1998.Google Scholar
  52. 52.
    Reske S.N., Grillenberger K.G., Glatting G., Port M., Hildebrandt M., Gansauge E, and Beger H.G. Overexpression of glucose transporter 1 and increased FDG uptake in pancreatic carcinoma, J. Nucl. Med. 38 (9): 1344–1348, 1997.PubMedGoogle Scholar
  53. 53.
    Prip Buus C., Bouthillier Voisin A.C., Kohl C., Demaugre E, Girard J., and Pegorier J.P. Evidence for an impaired long-chain fatty acid oxidation and ketogenesis in FAO hepatoma cells, Eur. J. Biochem. 209 (1): 291–298, 1992.CrossRefGoogle Scholar
  54. 54.
    Boros L.G., Lee P.W., Brandes J.L., Cascante M., Muscarella P., Schirmer W.J., Melvin W.S., and Ellison E.C. Nonoxidative pentose phosphate pathways and their direct role in ribose synthesis in tumors: is cancer a disease of cellular glucose metabolism?, Med. Hypotheses 50 (1): 55–59, 1998.CrossRefGoogle Scholar
  55. 55.
    Fields A.L., Wolman S.L., Cheema-Dhadli S., Morris H.P., and Halperin M.L. Regulation of energy metabolism in Morris hepatoma 7777 and 7800, Cancer Res. 41 (7): 2762–2766, 1981.PubMedGoogle Scholar
  56. 56.
    Tisdale M.J. and Brennan R.A, Loss of acetoacetate coenzyme A transferase activity in tumours of peripheral tissues, Br. J. Cancer 47 (2): 293–297, 1983.PubMedCrossRefGoogle Scholar
  57. 57.
    Colquhoun A. and Curi R. Human and rat tumour cells possess mitochondrial carnitine palmitoyltransferase I and II: effects of insulin, Biochem. Mol. Biol. Int. 37 (4): 599–605, 1995.Google Scholar
  58. 58.
    Colquhoun A., de Mello F.E., and Curi R. In vivo inhibition of Walker 256 tumour carnitine palmitoyltransferase I by soya oil dietary supplementation, Biochem. Mol. Biol. Int. 44 (1): 151–156, 1998.Google Scholar
  59. 59.
    Evans R.D. and Williamson D.H. Tissue-specific effects of rapid tumour growth on lipid metabolism in the rat during lactation and on litter removal, Biochem. J. 252 (1): 65–72, 1988.PubMedGoogle Scholar
  60. 60.
    Seelaender M.C., Curi R., Colquhoun A., Williams J.F., and Zammit V.A. Carnitine palmitoyltransferase II activity is decreased in liver mitochondria of cachectic rats bearing the Walker 256 carcinosarcoma: effect of indomethacin treatment, Biochem. Mol. Biol. Int. 44 (1): 185–193, 1998.Google Scholar
  61. 61.
    Siddiqui R.A. and Williams J.F. The regulation of fatty acid and branched-chain amino acid oxidation in cancer cachectic rats: a proposed role for a cytokine, eicosanoid, and hormone trilogy, Biochem. Med. Met. Biol. 42 (1): 71–86, 1989.CrossRefGoogle Scholar
  62. 62.
    Seelaender M.C., Costa-Rosa LE, and Curi R. Fatty acid oxidation in lymphocytes from Walker 256 tumor-bearing rats, Braz. J. Med. Biol. Res. 29 (4): 445–451, 1996.PubMedGoogle Scholar
  63. 63.
    Noguchi Y., Vydelingum N.A., and Brennan M E Tumor-induced alterations in hepatic malic enzyme and carnitine palmitoyltransferase activity, J. Surg. Res. 55 (4): 357–363, 1993.PubMedCrossRefGoogle Scholar
  64. 64.
    Yazdanpanah M, Luo X., Lau R., Greenberg M., Fisher L.J., and Lehotay D.C. Cytotoxic aldehydes as possible markers for childhood cancer, Free Radic. Biol. Med. 23 (6): 870–878, 1997.PubMedCrossRefGoogle Scholar
  65. 65.
    Sachan D.S. and Dodson W.L. The serum carnitine status of cancer patients, J. Am. Coll. Nutr. 6 (2): 145–150, 1987.PubMedGoogle Scholar
  66. 66.
    Rössle C., Pichard C., Roulet M., Bergstrom J., and Furst P. Muscle carnitine pools in cancer patients, Clin. Nutr. 8 (6): 341–346, 1989.Google Scholar
  67. 67.
    Dodson W.L., Sachan D.S., Krauss S., and Hanna W. Alterations of serum and urinary carnitine profiles in cancer patients: hypothesis of possible significance, J. Am. Coil. Nutr. 8 (2): 133–142, 1989.Google Scholar
  68. 68.
    Willson J., Weese J., Wolberg W, and Shug A. Differences between normal and cancerous human colon in carnitine (C) and CoA levels, AACR Annual Meeting, San Diego, California 25–28/5/1983.Google Scholar
  69. 69.
    De la Morena E., Montero C., and De la Vieja J. Low levo-carnitine levels in serum of women with early breast tumors,International Conference Predictive Drug Testing on Human Tumor Cells. Zurich, 20–23/7/1983.Google Scholar
  70. 70.
    Schlenzig J.S., Charpentier C., Rabier D., Kamoun P., Sewell A.C., and Harpey J.P. L-Carnitine: a way to decrease cellular toxicity of ifosfamide?, Eur. J. Pediatr. 154 (8): 686–687, 1995.PubMedCrossRefGoogle Scholar
  71. 71.
    Berardi S., Heuberger W, Jacky E., and Krahenbuhl S. Renal carnitine excretion is a marker for cisplatin-induced tubular nephrotoxicity, Faseb J. 10 (3): A470, 1996.Google Scholar
  72. 72.
    Heuberger W., Berardi S., Jacky E., Pey P., and Krahenbuhl S. Increased urinary excretion of carnitine in patients treated with cisplatin, Eur. J. Clin. Pharmacol. 54 (7): 503–508, 1998.PubMedCrossRefGoogle Scholar
  73. 73.
    Goormaghtigh E., Brasseur R., Huart P., and Ruysschaert J.M. Study of the adriamycin-cardiolipin complex structure using attenuated total reflection infrared spectroscopy, Biochemistry 26 (6): 1789–1794, 1987.PubMedCrossRefGoogle Scholar
  74. 74.
    Robinson N.C. Functional binding of cardiolipin to cytochrome c oxidase, J. Bioenerg. Biomembr 25 (2): 153–163, 1993.CrossRefGoogle Scholar
  75. 75.
    Demant E.J. Inactivation of cytochrome c oxidase activity in mitochondrial membranes during redox cycling of doxorubicin, Biochem. Pharmacol. 41 (4): 543–552, 1991.Google Scholar
  76. 76.
    Iliskovic N., Panagia V., Slezak J., Kumar D., Li T., and Singal P.K. Adriamycin depresses in vivo and in vitro phosphatidylethanolamine N-methylation in rat heart sarcolemma, Mol. Cell. Biochem. 176 (1–2): 235–240, 1997.CrossRefGoogle Scholar
  77. 77.
    Brady L.J. and Brady P.S. Hepatic and cardia carnitine palmitoyltransferase activity. Effects of adriamycin and galactosamine, Biochem. Pharmacol. 36 (20): 3419–3423, 1987.Google Scholar
  78. 78.
    Kashfi K., Israel M., Sweatman T.W., Seshadri R., and Cook G.A. Inhibition of mitochondrial carnitine palmitoyltransferases by adriamycin and adriamycin analogues, Biochem. Pharmacol. 40 (7): 1441–1448, 1990.Google Scholar
  79. 79.
    Abdel-aleem S., el-Merzabani M.M., Sayed-Ahmed M., Taylor D.A., and Lowe J.E. Acute and chronic effects of adriamycin on fatty acid oxidation in isolated cardiac myocytes, J. Mol. Cell. Cardiol. 29 (2): 789–797, 1997.PubMedCrossRefGoogle Scholar
  80. 80.
    Payne C.M. A quantitative analysis of leptomeric fibrils in an adriamycin/carnitine chronic mouse model, J. Submicrosc. Cytol. 14 (2): 337–45, 1982.PubMedGoogle Scholar
  81. 81.
    McFalls E.O., Paulson D.J., Gilbert E.F., and Shug A.L. Carnitine protection against adriamycininduced cardiomyopathy in rats, Life Sci. 38 (6): 497–505, 1986.PubMedCrossRefGoogle Scholar
  82. 82.
    Torresi U., Miseria S., Piga A., Cellerino R., Quacci D., Dell’orbo C., and Murer B. An ultrastructural study of the protective effect of L-carnitine against cardiotoxicity of anthracyclines in experimental animals, Clin. Trials. J. 27 (2): 128–140, 1990.Google Scholar
  83. 83.
    Vick J.A., De Felice S.L., and Barranco I.S. Prevention of adrianycin induced cardiac toxicity with carnitine: a study in primates, Pharmacodynamies & Therapeutics (Life Sci Adv) 9: 1–5, 1990.Google Scholar
  84. 84.
    Neri B., Comparini T., Miliani A., and Torcia M. Protective effects of L-carnitine on acute adriamycin and daunomycin cardiotoxicity in cancer patients. A preliminary report, Clin. Trials J. 20 (2): 98–103, 1983.Google Scholar
  85. 85.
    Gulizia M, Cardillo R., Olivieri M., Raciti S., Tosto A., Valadà E, and Circo A. Valutazione funzionale cardiaca in pazienti oncologici in trattamento con adriamicina, Clin. Europea 2: 1–40, 1984.Google Scholar
  86. 86.
    Durante C., Ghio R., Ratti M., Dototero D., Dejana A., Gatti A., Minale P., and Boccaccio P. Valutazione della cardiotossicità da antraciclinici mediante test enzimatico: possibile ruolo protettivo della L-carnitina, XXX Congresso Nazionale della Società Italiana di Ematologia, Palermo 6–11/10/1985.Google Scholar
  87. 87.
    Anselmi G., Alvarez M., Strauss M., Gonzales M.I., Gomez J.R., Lopez J.R., Suarez C., Mathison Y., and Horvat D. Indicaciones de la L-carnitina en cardiologia pediatrica, Rev. Latina Cardiol. 12 (3): 137–145, 1991.Google Scholar
  88. 88.
    Anselmi G., Chazzim G., Eleizalde G., Machado H.I., Mathison Y., Alvarez M., and Strauss M. Prevention of adriamycin (ADM) cardiotoxicity with L-carnitine. Results in 100 children treated for different types of tumors. World Congress of Pediatric Cardiology and Cardiac Surgery. Paris, 21–25/6/1993, pp. 24–51.Google Scholar
  89. 89.
    Alberts D.S., Peng Y.M., Moon T.E., and Bressler R. Carnitine prevention of adriamycin toxicity in mice, Biomedicine 29 (8): 265–268, 1978.PubMedGoogle Scholar
  90. 90.
    Senekowitsch R., Lohninger A., Kriegel H., Staniek H., Krieglsteiner H., and Kaiser E. Protective effects of carnitine on adriamycin toxicity to heart, In: Kaiser E. “Carnitine-Its role in lung and heart disorders”. Karger, Basel, pp. 126–137, 1987.Google Scholar
  91. 91.
    Culbreath A., Howard E.F., and Carter A.L. Lack of an effect of carnitine on the chemotherapeutic properties of adriamycin towards human pancreatic cells, FASEB Fed Am Soc Exp Biol J 3(4):Al264, 1989.Google Scholar
  92. 92.
    Carter A.L., Pierce R., Culbreath C., and Howard E. Conjunctive enhancement of adriamycin by carnitine. In: Carter AL “Current concepts in carnitine research”. Crc Press, Inc, pp. 245–251, 1992.Google Scholar
  93. 93.
    Thomitzek W.D. and Strack E. The effect of palmitoylcarnitine on Ehrlich ascites tumor cells in vitro and in vivo. Acta Biol. Med. Ger. 17 (2): 145–159, 1966.Google Scholar
  94. 94.
    Nakadate T. and Blumberg P.M. Modulation by palmitoylcarnitine of protein kinase C Activation, Cancer Res. 47 (24 Pt 1): 6537–6542, 1987.PubMedGoogle Scholar
  95. 95.
    Nakaki T., Mita S., Yamamoto S., Nakadate T., and Kato R. Inhibition by palmitoylcarnitine of adhesion and morphological changes in HL-60 cells induced by 12-O-tetradecanoylphorbol-13-acetate, Cancer Res. 44 (5): 1908–1912, 1984.PubMedGoogle Scholar
  96. 96.
    Butler A.P., Mar P.K., McDonald F.F., and Ramsay R.L. Involvement of protein kinase C in the regulation of ornithine decarboxylase mrna by phorbol esters in rat hepatoma cells, Exp. Cell Res. 194 (1): 56–61, 1991.PubMedCrossRefGoogle Scholar
  97. 97.
    Aizu E., Yamamoto S., Nakadate T., Kiyoto I., and Kato R. Palmitoylcarnitine reverses 12–0tetradecanoylphorbol 13-acetate-induced refractory state for the TPA-caused ornithine decarboxylase induction in mouse epidermis, Carcinogenesis 9 (2): 309–313, 1988.PubMedCrossRefGoogle Scholar
  98. 98.
    Satyamoorthy K. and Perchellet J.P. Inhibition of mouse skin tumor promotion by adriamycin and daunomycin in combination with verapamil or palmitoylcarnitine, Cancer Lett. 55: 135–142, 1990.PubMedCrossRefGoogle Scholar
  99. 99.
    Vescovi G., Weber B., Matrat M., Ramacci C., Nabet E, and Kmemer B. Modulation by palmitoylcarnitine of calcium activated, phospholipid-dependent protein kinase activity and inhibition of melanoma cell growth, Br. J. Dermatol. 119 (2): 171–178, 1988.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1999

Authors and Affiliations

  • Menotti Calvani
    • 1
  • Raffaela Nicolai
    • 1
  • Alfonso Barbarisi
    • 2
  • Emilia Reda
    • 1
  • Paola Benatti
    • 1
  • Gianfranco Peluso
    • 3
  1. 1.Scientific DepartmentSigma Tau S.p.A.RomeItaly
  2. 2.Institute of Clinical Surgery, Faculty of Medicine2 University of NaplesItaly
  3. 3.CNR, Via Toiano 6, Arco Felice (Naples)2 University of NaplesItaly

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