Differential modulation of the mevalonate pathway by diverse Lippia alba chemotypes

MONTERO VILLEGAS S; CICCIO ALBERTI JF; CASTRO A; POLO MP; GARCIA DE BRAVO, MM

Mendoza

Congreso; XLVIII Reunión Anual de SAIB; 2012

SAIB

Lippia alba (Mill) N.E.Br. is a plant with several chemotypes (CHMs) commonly used in traditional medicine. The biological activity of these plants are attributed to their essential oils (EOs). These EOs present a diverse and high concentration of monoterpenes characteristic of each CHM. Many monoterpenes exhibit antitumor activity that has been attributed to multiple pharmacological effects on the mevalonate pathway (MP). We have reported that EOs of  tagetenone (T), carvone (Ca), piperitone (P) and citral (C) CHMs inhibit cell proliferation (CP) in HepG2 and A549 cells. The aim of this work was to study the effects of these EOs on the MP in these cell lines. Cells were treated with increasing non inhibitory CP doses of EOs. Incorporation of 14C-acetate into intermediates and final products of the MP was determined by autoradiography of nonsaponifiable lipids separated by TLC. Exogenous cholesterol (CHO) uptake and outflow were evaluated. CHO synthesis was inhibited in a dose-dependent manner with all EOs. Synthesis of other products decrease proportionaly with P, whereas with Ca, C, and T an increase in ubiquinone and other intermediates was observed. This increase was more markedly in A549 cells. These findings suggest that different synergic effects of  monoterpenes present in the EOs modulate the MP at different levels, some of them at a later step of the ramification point.