Inhibition of the putrescine-mediated cell growth by the antimalarial mepacrine.

A problem strictly related to the spreading of malaria, is immunocompromission whichmakes patients more vulnerable to bacterial and viral infections and to other illness suchas tumour. We recently demonstrated that some antimalarials can modify the growth ofnormal and tumoural cells (1). Mepacrine, was found to be a potent inhibitor of VERO andMCF-7 cell growth. Like chloropromazine, a drug used in the treatment of prion disease,mepacrine possesses an aliphatic chain very similar to that of putrescine, a naturalpolyamine whose concentration in biological tissues is crucial for cells, but in particular forprions proliferation. Aim of our study was to investigate if mepacrine could antagonize theproliferative effect of putrescine. VERO and MCF-7 cells were cultured in MEM medium andtreated with increasing concentrations of putrescine, mepacrine and their association.MTT test was performed. Results show that putrescine significantly stimulated the growthof VERO and MCF-7 cells, whereas mepacrine confirmed to be a potent inhibitor. Whenused in association, sub-inhibitory concentrations of mepacrine antagonized the proliferativeeffect of putrescine on both cell cultures (inhibition >60%). The presence of thealiphatic chain in mepacrine, and putrescine, could explain this interaction. Finally, sinceit has been postulated by Prousiner (2) that the variation in the concentration ofpolyamines stimulates the proliferation of prions, on the basis of these preliminary data,we can assume that, similarly to chlorpromazine, mepacrine could be useful in thetreatment of prion diseases.