Variations in polyamine concentration are observed in case of neurodegenerative illness. Theantimalarial quinacrine is an alkylating agent characterised by the presence of an aliphatic chainsimilar to that of putrescine and spermine, two polyamines whose activation is closely associatedwith cell proliferation. Airn of the present study was the evaluation of the effect of quinacrine andpolyamines, alone and in combination, on glioblastomas cell replication. Methods: Humanglioblastomas cells (U87-MG) were cultured in EMEM (+37"C in 5% COL in air) and treated withincreasing concentrations of quinacrine (from 3.3 microM to 100 microM), putrescine (from 0.05 microM to 0.5microM), spermine ( from 0.5 microM to 10 microM) and quinacrine plus putrescine or spermine. Results FomMTT test showed that putrescine and spermine 0.5 microM significantly stimulate U87-MG cell growth(+53.86% and + 28% respectively), whereas quinacrine confirmed to be a potent cell inhibitor. Thecombination of sub-inhibitory concentrations of quinacrine (34 microM) plus putrescine (0.5 microM)resulted in a significant inhibition (-63%) of cell replication, but the same inhibitory effect (-26%)was reached using a lower concentration of quinacrine (17microM). The same results (- 64.57% and -28%) were obtained fiom the combination quinacrine (34 microM)/spermine (0.5 microM) and quinacrine(17microM)/spermine (0.5 microM). Preliminary results from the western blotting test performed on U87-MG cells indicate that the bcl-2 expression seems to be reduced in the cultures treated with thecombiitions polyamine/quinacrine (34 microM) Conclusion: Natural polyamines putrescine andspermine added to U87-MG cell cultures significantly stimulate cell growth. Quinacrine lowconcentration (17microM) antagonises cell proliferation induced by the polyamines. We suppose thatthe presence of the aliphatic chain both in quinacrine and in polyamines could be at the basis of thisinteraction. If our hypothesis will be confirmed, it will be possible to postulate the use of lowconcentrations of quinacrine in the treatment of neurodegenerative illness or malignancies inducedby variations in polyamine levels in human brain.

Potential Role of the Antimalarial Quinacrine as Antiproliferative Agent in Neurodegenerative Illness / A., Coppi; Baggio, Giosuè Gabriele; E., Bruni; Rossi, Tiziana. - STAMPA. - UNICO:(2007), pp. 45-45. ((Intervento presentato al convegno COST ACTION B22 DRUG DEVELOPFOR PARASITIC DIS tenutosi a Modena nel 19-20 febbraio 2007.

Potential Role of the Antimalarial Quinacrine as Antiproliferative Agent in Neurodegenerative Illness.

BAGGIO, Giosuè Gabriele;ROSSI, Tiziana
2007

Abstract

Variations in polyamine concentration are observed in case of neurodegenerative illness. Theantimalarial quinacrine is an alkylating agent characterised by the presence of an aliphatic chainsimilar to that of putrescine and spermine, two polyamines whose activation is closely associatedwith cell proliferation. Airn of the present study was the evaluation of the effect of quinacrine andpolyamines, alone and in combination, on glioblastomas cell replication. Methods: Humanglioblastomas cells (U87-MG) were cultured in EMEM (+37"C in 5% COL in air) and treated withincreasing concentrations of quinacrine (from 3.3 microM to 100 microM), putrescine (from 0.05 microM to 0.5microM), spermine ( from 0.5 microM to 10 microM) and quinacrine plus putrescine or spermine. Results FomMTT test showed that putrescine and spermine 0.5 microM significantly stimulate U87-MG cell growth(+53.86% and + 28% respectively), whereas quinacrine confirmed to be a potent cell inhibitor. Thecombination of sub-inhibitory concentrations of quinacrine (34 microM) plus putrescine (0.5 microM)resulted in a significant inhibition (-63%) of cell replication, but the same inhibitory effect (-26%)was reached using a lower concentration of quinacrine (17microM). The same results (- 64.57% and -28%) were obtained fiom the combination quinacrine (34 microM)/spermine (0.5 microM) and quinacrine(17microM)/spermine (0.5 microM). Preliminary results from the western blotting test performed on U87-MG cells indicate that the bcl-2 expression seems to be reduced in the cultures treated with thecombiitions polyamine/quinacrine (34 microM) Conclusion: Natural polyamines putrescine andspermine added to U87-MG cell cultures significantly stimulate cell growth. Quinacrine lowconcentration (17microM) antagonises cell proliferation induced by the polyamines. We suppose thatthe presence of the aliphatic chain both in quinacrine and in polyamines could be at the basis of thisinteraction. If our hypothesis will be confirmed, it will be possible to postulate the use of lowconcentrations of quinacrine in the treatment of neurodegenerative illness or malignancies inducedby variations in polyamine levels in human brain.
COST ACTION B22 DRUG DEVELOPFOR PARASITIC DIS
Modena
19-20 febbraio 2007
UNICO
45
45
A., Coppi; Baggio, Giosuè Gabriele; E., Bruni; Rossi, Tiziana
Potential Role of the Antimalarial Quinacrine as Antiproliferative Agent in Neurodegenerative Illness / A., Coppi; Baggio, Giosuè Gabriele; E., Bruni; Rossi, Tiziana. - STAMPA. - UNICO:(2007), pp. 45-45. ((Intervento presentato al convegno COST ACTION B22 DRUG DEVELOPFOR PARASITIC DIS tenutosi a Modena nel 19-20 febbraio 2007.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11380/420908
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