Title:Antitumor Effect of Pomolic Acid in Acute Myeloid Leukemia Cells Involves Cell Death, Decreased Cell Growth and Topoisomerases Inhibition
Volume: 18
Issue: 10
Author(s): Michelle X.G. Pereira, Amanda S.O. Hammes, Flavia C. Vasconcelos, Aline R. Pozzo, Thaís H. Pereira, Ernesto R. Caffarena, Cerli R. Gattass and Raquel C. Maia*
Affiliation:
- Laboratorio de Hemato-Oncologia Celular e Molecular, Programa de Pesquisa em Hemato-Oncologia Molecular, Instituto Nacional de Cancer (INCA), Rio de Janeiro, (RJ),Brazil
Keywords:
Acute myeloid leukemia, natural compound, pomolic acid, human DNA topoisomerases, Topo I, Topo IIα, anticancer agent, drug
discovery.
Abstract: Background: Acute myeloid leukemia (AML) represents the largest number of annual deaths from
hematologic malignancy. In the United States, it was estimated that 21.380 individuals would be diagnosed with
AML and 49.5% of patients would die in 2017. Therefore, the search for novel compounds capable of increasing
the overall survival rate to the treatment of AML cells is urgent.
Objectives: To investigate the cytotoxicity effect of the natural compound pomolic acid (PA) and to explore the
mechanism of action of PA in AML cell lines with different phenotypes.
Methods: Three different AML cell lines, HL60, U937 and Kasumi-1 cells with different mechanisms of resistance
were used to analyze the effect of PA on the cell cycle progression, on DNA intercalation and on human
DNA topoisomerases (hTopo I and IIα) in vitro studies. Theoretical experiments of the inhibition of hTopo I and
IIα were done to explore the binding modes of PA.
Results: PA reduced cell viability, induced cell death, increased sub-G0/G1 accumulation and activated
caspases pathway in all cell lines, altered the cell cycle distribution and inhibited the catalytic activity of both
human DNA topoisomerases.
Conclusion: Finally, this study showed that PA has powerful antitumor activity against AML cells, suggesting
that this natural compound might be a potent antineoplastic agent to improve the treatment scheme of this
neoplasm.
