Natural triterpenoids from Cecropia lyratiloba are cytotoxic to both sensitive and multidrug resistant leukemia cell lines.
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.
Rocha
Gleice da Graça
Gda G
Lab. de Imunologia Celular, Instituto de Biofísica Carlos Chagas Filho, CCS B1 G, Universidade Federal do Rio de Janeiro, 21949-900 Rio de Janeiro, RJ, Brazil.
Simões
Marisol
M
Lúcio
Kelly Araujo
KA
Oliveira
Rodrigo Rodrigues
RR
Coelho Kaplan
Maria Auxiliadora
MA
Gattass
Cerli Rocha
CR
D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D035702:Cecropia Plant / Q000737:chemistry*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000188:drug therapy*; D008968:Molecular Conformation; D018517:Plant Roots / Q000737:chemistry*; D012680:Sensitivity and Specificity; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*
D000970:Antineoplastic Agents; D014315:Triterpenes; C007695:euscaphic acid