Antiproliferative efficacy of diverse Lippia alba chemotypes on the mevalonate pathway

MONTERO VILLEGAS S; CICCIÓ ALBERTI JF; POLO M; GARCÍA DE BRAVO MM

Potrero de los Funes

Congreso; XLVII Reunión Anual de SAIB; 2011

SAIB

Lippia alba (Mill.) N. E. Brown is an aromatic shrub widely used as folk medicine in America. There are many chemotypes (CHM) of L. alba essential oil (EO) mainly due to its wide geographical extension. Each EO has a different composition of monoterpenes qualitatively and quantitatively. Several monoterpenes have an antiproliferative activity and synergistic effect, affecting the mevalonate pathway at multiple stages. The aim of this study is to evaluate the antiproliferative capacity of EOs of four CHMs with marked composition differences. HepG2 and A549 cells were treated with increasing concentrations of EOs from citral(C), piperitone(P), tagetenone(T) and carvone(Ca) CHMs. Cellular proliferation (CP) was determined by MTT assay. C and T CHMs that are composed predominantly of acyclic monoterpenes present an IC50 ten times lower than P and Ca CHMs whose composition is mainly of cyclic ones. This would indicate that acyclic monoterpenes have a higher efficacy in the CP inhibition. To analyze the effect of T CHM at non inhibitory CP doses in the mevalonate pathway, the incorporation of 14C acetate in intermediates and final products were determinated. A dose dependent decrease in the cholesterol synthesis and increase of ubiquinone and some intermediaries were observed, suggesting an inhibition of cholesterogenesis at a latter phase from the ramification point of the pathway.