Autophagy inhibited Ehrlich ascitic tumor cells apoptosis induced by the nitrostyrene derivative compounds: Relationship with cytosolic calcium mobilization

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Apoptosis induction is often associated with increased autophagy, indicating interplay between these two important cellular events in cell death and survival. In this study, the programmed cell death and autophagy induced by two nitrostyrene derivative compounds (NTS1 and NTS2) was studied using the tumorigenic Ehrlich ascitic tumor (EAT) cells. EAT cells were highly sensitive to NTS1 and NTS2 cytotoxicity in a dose-dependent manner. NTS1 and NTS2 IC50 was less than 15.0 mu M post 12 h incubation. Apoptosis was primarily induced by both compounds, as demonstrated by an increase in Annexin-V positive cells, concurrently with cytochrome c release from mitochondria to cytosol and caspase-3 activation. Although cytosolic Ca2+ mobilization is involved in autophagy as well as apoptosis in response to cellular stress in many cancer cell types, from the two nitrostyrene derivative compounds studied, mainly NTS1 mobilized this ion and disparate autophagy in EAT cells. These results suggest that EAT induced cell death by NTS1 and NTS2 involved a Ca2+-dependent and a Ca2+-independent pathways, respectively. In accordance with these results, the treatment of EAT cells with 3 methyladenine (3-MA), an autophagy inhibitor; significantly increased the number of apoptotic cells after NTS1 treatment, suggesting that pharmacological modulation of autophagy augments the NTS1 efficacy. Thus, we denote the importance of studies involving autophagy and apoptosis during pre-clinical studies of new drugs with anticancer properties. (C) 2011 Elsevier B. V. All rights reserved.67841699614Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

On the Young Savannas in the Land of Ancient Forests

Covering ancient geomorphological landscapes, and surrounded by some of the most diverse forests on Earth, the Neotropical savannas were once perceived by naturalists as ancient environments. However, current evidence suggests that tropical forests have existed in the Neotropics since the Paleocene, whereas most plant lineages present in South American savannas are recently derived from clades from the surrounding forested biomes. This chapter provides a multidisciplinary overview on the origin, assembly and expansion of Neotropical savannas, with focus on South America. For this, we consider available evidence from the fossil record, paleoenvironmental proxies (phytoliths), and phylogenetic information for both plants and animals. Paleoenvironmental reconstructions indicate suitable climates for central South American savannas since the middle Miocene, which is also when molecular phylogenies indicate the origin of some vertebrate groups typical of savannas. Fossil data indicate the ecological expansion of both C3 and C4 grasses in southern South America by the late Miocene. Fossil information also indicates the onset of savannas in northern South America during the Pliocene, a period in which most woody plants of the largest extension of Neotropical savannas (the Cerrado) are thought to have diversified, as inferred by dated phylogenies. Although the combined lines of evidence indicate that Neotropical savannas in South America are indeed younger than their surrounding forests, the precise timing and factors that influenced the origin, assembly and expansion of Neotropical savannas remain contentious. Future research should aim at (1) increasing and integrating knowledge about the diversification of important taxa characteristic to Neotropical savannas, (2) establishing continuous sequences of fossils, and (3) building accurate paleoenvironmental reconstructions for the entire Neogene