One of the mechanisms found both in cancer cells and in pathogenic microorganisms that lead to an inefficient treatment of some diseases is the drug efflux mediated by membrane proteins of the super family of the ABC Transporters. The transporter Pdr5p of S. cerevisiae presents high homology with the mammalian P-glycoprotein and with other fungal ABC pumps, which makes it a useful model for the of study multidrug resistance. One of the strategies to overcome this kind of resistance is use of protein inhibitors, but the drugs available at this moment show many side effects.
Plant extracts could be an interesting alternative to find new compounds with inhibitory effect on ABC proteins related with drug efflux, allowing cells to recover their sensitivity to available drugs.
In this study we have evaluated the effects of the ethanolic extract of Lippia lacunosa and Lippia rotundifolia and its partitions, obtained with solvents of growing polarities (hexane, dichloromethane, ethyl acetate and buthanol) on Pdr5p ATPase activity, measured as described by Fiske&Subbarow (1925). All the partitions were dried and solubilized with dimethylsulfoxide and then tested on fix concentration of 400 mg/ml. The partitions in dichloromethane of both plants extracts were selected for further analysis due to its best inhibition of the ATPase activity. The maximum inhibition obtained using dichloromethane partition from Lippia lacunosa and Lippia rotundifolia were 61,5% and 72,6% respectively, in relation to control without extract. Further investigations using intact cells are being done in order to check the effect of the same partition in the development of the cells in culture medium.