Tucumã extracts decreases PML/RARΑ gene expression in NB4/APL cell line

Keywords: Astrocaryum aculeatum, ATRA, Carotenoids, Leukemia, Differentiation syndrome

Abstract

Acute promyelocytic leukemia (APL) is a cancer pharmacologically treated with all-trans retinoic acid (ATRA), although well tolerated by most patients, some develop toxicity to ATRA, Differentiation Syndrome. The Amazon Biome has several fruits and oil plants rich in micronutrients, particularly carotenoids as the fruit tucumã (Astrocaryum aculeatum). This study analyzed the antitumor and cytoprotective activity of tucumã with and without concomitant exposure of ATRA in high concentration mimicking the toxicity of differentiation syndrome, as the potential cytotoxic effect of chemotherapeutic in an APL cell line. The cultured NB4 cells were exposed to ethanolic extracts of tucumã and to synergism with extracts and ATRA. Determination of proliferation, cell viability, caspases 1, 3, 8 and cell differentiation by nested RT-qPCR. The ATRA control had a strong inhibitory effect and toxicity as expected. The extracts also reduced cell proliferation by triggering apoptosis in concentration-dependent and reversing chromosome translocation, especially the lowest tested concentration of tucumã pulp extract. In the synergism, extracts act to maintain the levels of viability and apoptosis equal to the ATRA control but in contrast to drug that causes death and destruction of the genetic material, tucumã demonstrated a reduction of the gene expression indicating a possible protection against the toxicity of high concentrations of ATRA. These results suggest that fruits rich in retinoid molecules may have a cytotoxic effect against APL cells and reduced concentrations of carotenoids may act as cytoprotectors in APL cells treated with high concentrations of ATRA promoting cellular/molecular differentiation.

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Author Biographies

Priscila Marquezan Copetti, Universidade Franciscana

Programa de Pós-graduação em Nanociências

Pablo Sebastian de Britto Oliveira, Universidade Federal de Santa Maria

Medicina Veterinária

Luis Felipe Machado Garcia, Universidade Federal de Santa Maria

Departamento de Morfologia

Rodrigo Almeida Vaucher, Universidade Federal de Pelotas

Health Sciences

Marta Medeiros Frescura Duarte, Universidade Federal de Santa Maria

Health Sciences

Ivana Beatrice Mânica da Cruz, Universidade Federal de Santa Maria

Departamento de Morfologia

Aline Ferreira Ourique, Universidade Franciscana

Programa de Pós-graduação em Nanociências

Michele Rorato Sagrillo, University Franciscana

Health Sciences

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Published
28-06-2019
How to Cite
Copetti, P., Oliveira, P., Garcia, L., Vaucher, R., Duarte, M., Krause, L., Cruz, I., Ourique, A., & Sagrillo, M. (2019). Tucumã extracts decreases PML/RARΑ gene expression in NB4/APL cell line. Archives in Biosciences & Health, 1(1), 77-98. https://doi.org/10.18593/abh.17200
Section
Articles - Original research