euscaphic-acid and Leukemia

The cytotoxicity of four triterpenoids, euscaphic acid (1), tormentic acid (2), 2alpha-acetyl tormentic acid (3), and 3beta-acetyl tormentic acid (4), isolated from the roots of Cecropia lyratiloba (Moraceae) by countercurrent chromatography, was evaluated in vitro in sensitive and multidrug resistant leukemia cell lines. A structure/activity relationship analysis of the compounds was performed. Acetylation of compound 2 at C2 increased its activity by a factor of 2 while acetylation at C3 had a smaller effect. Compound 1 induces death by activation of caspase-3, dependent apoptotic pathway. Furthermore, the four triterpenoids were also active toward a multidrug resistant (MDR) leukemia cell line, overexpressing glycoprotein-P (P-gp). These results reveal the potential of the terpenoids as source for the development of new anti-neoplastic and anti-MDR drugs.

Topics: Antineoplastic Agents; Apoptosis; Cecropia Plant; Cell Line, Tumor; Cell Survival; Dose-Response Relationship, Drug; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Humans; K562 Cells; Leukemia; Molecular Conformation; Plant Roots; Sensitivity and Specificity; Stereoisomerism; Structure-Activity Relationship; Triterpenes