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Evidence-Based Complementary and Alternative Medicine Volume 2019 ,2019-03-03
Cytotoxic and Apoptotic Activity of Majoranolide from Mezilaurus crassiramea on HL-60 Leukemia Cells
Research Article
Lanna M. Heemann 1 Kamylla F. S. de Souza 1 Danilo Tófoli 2 Kelly J. Filippin 1 Walmir S. Garcez 2 Maria de Fatima C. Matos 1 Fernanda R. Garcez 2 Renata T. Perdomo 1
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Received 2018-11-26, accepted for publication 2019-02-10, Published 2019-02-10

Majoranolide, a butanolide isolated from the nonpolar fraction of an ethanol extract of Mezilaurus crassiramea (Lauraceae) fruits, is being reported for the first time in this genus and the third time in plants. Structurally identified from 1D and 2D NMR and HRESIMS data, majoranolide proved cytotoxic against cancer cells—MCF-7 and MDA-MB-231 (breast), HT-29 (colon), PC-3 (prostate), 786-0 (renal), and HL-60 (leukemia)—inhibiting growth in HL-60 cells (GI50 = 0.21 μM) and exhibiting higher selectivity for this line than for nonneoplastic NIH/3T3 murine fibroblasts. Effects on the cell cycle, caspase-3 activation, and plasma membrane integrity were evaluated by flow cytometry. Expression of genes related to apoptotic pathways (BAX, BCL2, BIRC5, and CASP8) was investigated using RT-qPCR. At 50 μM, majoranolide induced cell cycle arrest at G1 in 24 h increased the sub-G1 population in 48 h and increased caspase-3 activation in a time-dependent manner. The compound upregulated BAX and CASP8 transcription (proapoptotic genes) and downregulated BIRC5 (antiapoptotic). Loss of plasma membrane integrity in 30% of cells occurred at 48 h, but not at 24 h, characterizing gradual, programmed death. The results suggest that majoranolide cytotoxicity involves apoptosis induction in HL-60 cells, although other mechanisms may contribute to this cell death.


Copyright © 2019 Lanna M. Heemann et al. 2019
This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Renata T. Perdomo.Laboratory of Molecular Biology and Cell Culture, School of Pharmaceutical Sciences, Food Technology, and Nutrition, Universidade Federal de Mato Grosso do Sul, Campo Grande, MS, Brazil, ufms.br.renataperdomo@gmail.com


Lanna M. Heemann,Kamylla F. S. de Souza,Danilo Tófoli,Kelly J. Filippin,Walmir S. Garcez,Maria de Fatima C. Matos,Fernanda R. Garcez,Renata T. Perdomo. Cytotoxic and Apoptotic Activity of Majoranolide from Mezilaurus crassiramea on HL-60 Leukemia Cells. Evidence-Based Complementary and Alternative Medicine ,Vol.2019(2019)



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