Pouterin, a novel potential cytotoxic lectin-like protein with apoptosis-inducing activity in tumorigenic mammalian cells

Pouterin, a novel potential cytotoxic lectin-like protein with apoptosis-inducing activity in tumorigenic mammalian cells

Author Boleti, Ana Paula de A. Google Scholar
Ventura, Claudio A. Google Scholar
Justo, Giselle Z. Autor UNIFESP Google Scholar
Silva, Rodrigo A. Google Scholar
Sousa, Ana Carolina T. de Google Scholar
Ferreira, Carmen V. Google Scholar
Yano, Tomomasa Google Scholar
Macedo, Maria Ligia R. Google Scholar
Institution Univ Fed Mat Grosso Sul
Universidade Estadual de Campinas (UNICAMP)
Universidade Federal de São Paulo (UNIFESP)
Abstract In this study, the cytotoxicity of pouterin in tumorigenic and non-tumorigenic mammalian cell lines was investigated. We found that HeLa, Hep-2 and HT-29 tumor cells were highly sensitive to pouterin cytotoxicity in a dose-dependent manner, whereas non-tumorigenic Vero cells and human lymphocytes were relatively resistant to the protein. Among the tumor cell lines, HeLa cells showed the highest susceptibility to pouterin cytotoxicity, exhibiting a time-dependent increase in LDH leakage and an IC50 value of 5 mu g/mL. Morphological alterations such as rounding, cell shrinkage and chromatin condensation, consistent with apoptotic cell death were observed. Apoptosis induction was demonstrated by DNA fragmentation as detected by terminal dUTP nick-end labeling (TUNEL). Furthermore, HeLa cells incubated with pouterin showed disruption of the actin cytoskeleton. Western blot analysis revealed that pouterin caused increased expression of p21, thus indicating cell cycle arrest. Subsequent studies provided evidence that apoptosis may be partially explained in the activation of the tumor necrosis factor receptor 1 (TNFR1) signaling. Interestingly, a time-dependent decrease of the expression of p65 nuclear factor kappa B (NF kappa B) subunit, concomitant with a downregulation of the inhibitor of apoptosis protein 1 (IAP1) was observed, suggesting that TNFR-mediated apoptosis is the predominant pathway induced by pouterin in HeLa cells. (c) 2008 Elsevier B.V. All rights reserved.
Keywords pouterin
HeLa cells
apoptosis
actin cytoskeleton
TNF receptor
Language English
Date 2008-06-15
Published in Toxicon. Oxford: Pergamon-Elsevier B.V., v. 51, n. 8, p. 1321-1330, 2008.
ISSN 0041-0101 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 1321-1330
Origin http://dx.doi.org/10.1016/j.toxicon.2008.03.007
Access rights Closed access
Type Article
Web of Science ID WOS:000257645200001
URI http://repositorio.unifesp.br/handle/11600/30734

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