Mepacrine Antagonises Tumour Cell Growth Induced by Natural Polyamines

Background: Mepacrine is an antiproliferative agent, characterised by an aliphaticchain similar to that of naturalpolyamineswhoseactivationiscloselyassociatedwith cell proliferation and may lead to malignant transformation andneurodegenerativediseases.Thisstudyaimstoinvestigate apossibleantagonismbetweenmepacrineandpolyaminesin tumourproliferation.MaterialsandMethods:MCF-7andVero cellswereculturedinEagle'sminimumessentialmediumand thensubjectedtogradedconcentrationsofputrescine,spermine and spermidine alone and in combination with mepacrine. Methyl thiazole tetrazolium test and Western-blotting were performed. Results: Putrescine and spermidine at 0.5 mg/l significantly stimulated cell growth, whereas mepacrine treatment confirmed the enhanced p21 expression previously reportedbyarecentstudyandgrowthinhibition.Whenusedin combination, mepacrine antagonized MCF-7 growth induced bypolyamines.Conclusion:Ourresultssuggestthatmepacrine mayrepresentachoiceinthetreatmentoftumoursinducedby themodifiedconcentrationofpolyamines. The natural polyamines putrescine, spermidine and spermine are small aliphatic amines whose concentration in biological tissues is crucial for cell growth since they interfere with nucleic acids activating both RNA t and RNA r (1). Considerable evidence has shown that polyamines play a critical role in breast cancer cell proliferation. In animal models and in in vitro studies, the depletion of polyamines resulted in a decrease of neoplastic cell proliferation (2-4). Mepacrine is an alkylating agent characterised by the presence of an aliphatic chain very similar to that found in natural polyamines (Figure 1). It is active against both resting and rapidly dividing cells, moreover it has been recognised as an inhibitor of ornithine decarboxylase (ODC) a crucial enzyme