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Apomorphine has a potent antiproliferative effect on Chinese hamster ovary cells

  • M. Scarselli
  • P. Barbier
  • F. Salvadori
  • M. Armogida
  • P. Collecchi
  • C. Pardini
  • F. Vaglini
  • R. Maggio
  • G. U. Corsini
Conference paper
Part of the 6th International Winter Conference on N eurodegeneration book series (NEURAL SUPPL, volume 55)

Summary

Apomorphine is a potent non selective agonist at the D1 and D2 dopamine receptors acting both pre- and post-synaptically. In this report we describe a novel function of apomorphine, independent from its dopaminergic activity. Apomorphine inhibits Chinese hamster ovary (CHO)-Kl cell proliferation in a dose-dependent manner. The EC50 of apomorphine-induced inhibition of CHO-K1 cell proliferation determined by cell counting was 3.24 ± 0.07 μM. Remarkably, the dose-response curve obtained by measuring the incorporation of [3H]thymidine was practically identical to the previous one giving an EC50 of 3.52 ± 0.04 μM. The dopaminergic antagonists SCH23390 and spiperone at a concentration of 10 μM (well beyond their Kd values for the dopamine D1 and D2-like receptors respectively) were not able to antagonize the effect of apomorphine on CHO-K1 cell proliferation. Apomorphine exerts its effect early during incubation; CHO-K1 cells exposed to apomorphine for a period as short as 1 h and then allowed to grow for three days were significantly reduced in number with respect to untreated control cells. After four hours of exposition to apomorphine (10 μM) the antiproliferative effect was similar to that seen when this compound was present in the bath for all three days. Concentrations of apomorphine higher than 10 μM induced cell death, and the colony was completely destroyed at 50μM. Cytometric analyses showed a significant accumulation of CHO-K1 cells in the G2/M phase.

Keywords

Dopamine Receptor Chinese Hamster Ovary Dihydropteridine Reductase Apomorphine Hydrochloride 100mM Potassium Phosphate Buffer 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Anden NE, Rubenson A, Fuxe K, Hokfelt T (1967) Evidence for dopamine receptor stimulation by apomorphine. J Pharm Pharmac 19: 627–629.CrossRefGoogle Scholar
  2. Ben-Shachar D, Riederer P, Youdim MBH (1991) Iron-melanin interaction and lipid peroxidation: implication for Parkinson’s disease. J Neurochem 57: 1609–1614.PubMedCrossRefGoogle Scholar
  3. Ernst AM (1967) Mode of action of apomorphine and dexamphetamine on gnawing compulsion in rats. Psychopharmacologia 10: 316–323.PubMedCrossRefGoogle Scholar
  4. Ferriola PC, Cody V, Middleton E Jr (1989) Protein kinase C inhibition by plant flavonoids. Kinetic mechanisms and structure-activity relationships. Biochem Pharmacol 38: 1617–1624.PubMedCrossRefGoogle Scholar
  5. Gassen M, Glinka Y, Pinchasi B, Youdim MBH (1996) Apomorphine is a highly potent free radical scavenger in rat brain mitochondrial fraction. Eur J Pharmacol 308: 219–225.PubMedCrossRefGoogle Scholar
  6. Gassen M, Grass A, Youdim MBH (1998) Apomorphine enantiomers protect cultured pheochromocytoma (PC12) cells from oxidative stress induced by H2O2 and 6-hydroxydopamine. Mov Disord 13: 242–248.PubMedCrossRefGoogle Scholar
  7. Graham DG (1978) Oxidative pathways for catecholamines in the genesis of neuromelanin and cytotoxic quinones. Mol Pharmacol 14: 633–643.PubMedGoogle Scholar
  8. Hastings TG, Zigmond MJ (1994) Identification of catechol-protein conjugates in neostriatal slices incubated with [3H]dopamine: impact of ascorbic acid and glutathione. J Neurochem 63: 1126–1132.PubMedCrossRefGoogle Scholar
  9. Iversen LL, Rogawski MA, Miller RJ (1976) Comparison of the effects of neuroleptic drugs on pre-and postsynaptic dopaminergic mechanism in the rat striatum. Mol Pharmacol 12: 251–262.PubMedGoogle Scholar
  10. Kang TB, Liang NC (1997) Studies on the inhibitory effects of quercetin on the growth of HL-60 leukemia cells. Biochem Pharmacol 54: 1013–1018.PubMedCrossRefGoogle Scholar
  11. Lal S (1988) Apomorphine in the evaluation of dopaminergic function in man. Prog Neuropsychopharmacol Biol Psychiatry 12: 117–164.PubMedCrossRefGoogle Scholar
  12. Lees AJ (1993) Dopamine agonists in Parkinson’s disease: a look at apomorphine. Fundam Clin Pharmacol 7: 121–128.PubMedCrossRefGoogle Scholar
  13. Liu J, Mori A (1993) Monoamine metabolism provides an antioxidant defense in the brain against oxidant-and free radical-induced damage. Arch Biochem Biophys 302: 118–127.PubMedCrossRefGoogle Scholar
  14. Matsukawa Y, Marui N, Sakai T, Satomi Y, Yoshida M, Matsumoto K, Nishino H, Aoike A (1993) Genistein arrests cell cycle progression at G2-M. Cancer Res 53: 1329–1331.Google Scholar
  15. Neumeyer JL, Neustadt BR, Weinhardt KK (1970) Aporphines. V. Total synthesis of (plus or minus)-apomorphine. J Pharm Sci 59:1850–1852.PubMedCrossRefGoogle Scholar
  16. Nishizuka Y (1989) Studies and prospectives of the protein kinase C family for cellular regulation. Cancer 63: 1892–1903.PubMedCrossRefGoogle Scholar
  17. Rosenberg PA (1988) Catecholamine toxicity in cerebral cortex in dissociated cell culture. J Neurosci 8: 2887–2894.PubMedGoogle Scholar
  18. Saari WS, King KK, Lotti KK (1973) Synthesis and biological activity of (6aS)-10,11-dihydroxyaporphine, the optical antipode of apomorphine. J Med Chem 16:171–172.PubMedCrossRefGoogle Scholar
  19. Shen RS, Smith KK, Davis PJ, Abell CW (1984) Inhibition of dihydropteridine reductase from human liver and rat striatal synaptosomes by apomorphine and its analogues. J Biol Chem 259: 8994–9000.PubMedGoogle Scholar
  20. Sheppard H, Wiggan G (1971) Different sensitivities of the phosphodiesterases (adenosine-3′,5′-cyclic phosphate 3′-phosphohydrolase) of dog cerebral cortex and erythrocytes to inhibition by synthetic agents and cold. Biochem Pharmacol 20: 2128–2130.PubMedCrossRefGoogle Scholar
  21. Wang BH, Lu ZX, Polya GM (1997) Inhibition of eukaryote protein kinases by isoquinoline and oxazine alkaloids. Planta Med 63(6): 494–498.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag/Wien 1999

Authors and Affiliations

  • M. Scarselli
    • 1
  • P. Barbier
    • 1
  • F. Salvadori
    • 1
  • M. Armogida
    • 1
  • P. Collecchi
    • 2
  • C. Pardini
    • 1
  • F. Vaglini
    • 1
  • R. Maggio
    • 1
  • G. U. Corsini
    • 1
  1. 1.Department of NeuroscienceUniversity of PisaItaly
  2. 2.Department of Oncology, Division of PathologyUniversity of PisaItaly

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