57º Congresso Brasileiro de Genética
Resumos do 57º Congresso Brasileiro de Genética • 30 de agosto a 2 de setembro de 2011
Centro de Convenções do Hotel Monte Real Resort • Águas de Lindóia • SP • Brasil
www.sbg.org.br - ISBN 978-85-89109-06-2
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(S)-Goniothalamin induces genotoxicity,
apoptosis and dowregulation in BIRC5
(survivin) gene in non-small cell lung cancer
cell line (NCI-H460)
Semprebon, SC1; Macedo Jr., FC2; de Fátima, A3; Lepri, S1; Sartori, D1; Ribeiro, LR4; Mantovani, MS1
1 - Department of Biology, State University of Londrina, Londrina, Paraná, Brazil. 2 - Department of Chemistry, State
University of Londrina, Londrina, Paraná, Brazil. 3 - Department of Chemistry, Federal University of Minas Gerais, Belo
Horizonte, Minas Gerais, Brazil. 4 - Department of Pathology, State University Paulista Julio de Mesquita Filho, Rio Claro,
São Paulo, Brazil.
[email protected]
Keywords: (S)-Goniothalamin, Survivin, BIRC5, Apoptosis, NCI-H460, Cytotoxicity
(R)-Goniothalamin (R-GNT) is a secondary metabolite found in plants of the genus Goniothalamus sp., which are common in Malaysia. This molecule has attracted the attention of researchers because of its selective cytotoxicity against
tumor cells and also by their ability to induce apoptosis. (S)-Goniothalamin (S-GNT) is a synthetic enantiomer of
(R)-Goniothalamin, although their mechanism remains unknown, studies indicate that to some cell lines this molecule
shows an antiproliferative activity higher than in natural form and also some differences in their mechanism. In this
study, we evaluate the effects of the S-GNT at concentrations of 2.5, 12.5 and 25 μM in cytotoxicity (MTT), kinetics
of cell proliferation, apoptosis, genotoxicity (Comet assay) and gene expression (RT-qPCR) of some apoptosis and
cell cycle genes (BAX, TP53 and BIRC5) in non-small cell lung cancer cell line (NCI-H460). Our results showed that
S-GNT decreased cell survival in a dose-dependent manner, significantly induced apoptosis (25 μM), likewise induced
genotoxicity at 2.5, 12.5 and 25 μM, and that the higher concentration significantly down-regulated BIRC5 gene expression (p=0,001, REST-384 software). Based on obtained data we suggest that the cytotoxicity observed after treatment with S-GNT occurred due to the potentiality of this molecule in bring DNA damage with consequent apoptosis
induction. Moreover, the significant reduction of mRNA levels BIRC5, the gene encoding protein survivin, was an
important finding first shown in this study and which may also explain the inhibition of cell proliferation and induce
apoptosis in tumor cells caused by this compound. The modulation of this gene expression is of great interest for the
development of new drugs for cancer therapy because it is overexpressed in tumor cells while normal cells are rarely
expressed and also by its inhibitory potential of apoptosis and cell cycle regulation, being an important factor for
tumor survival. Therefore, in accordance with the anti-apoptotic potential of survivin, we suggest that its down-regulation expression may be one of the mechanisms responsible for the induction of apoptosis and cell survival decrease
after exposure of NCI-H460 cells to S-GNT. In conclusion, our findings indicate S-GNT as a potential anticancer
agent, moreover, further studies should be conducted to elucidate how this molecule regulates BIRC5 expression.
Financial support: CAPES, CNPq, Fundação Araucária.