Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 678, Issue 1-3, Pages 6-14Publisher
ELSEVIER
DOI: 10.1016/j.ejphar.2011.12.031
Keywords
Nitrostyrene derivative compounds; Autophagy; Cancer cells; Apoptosis; Calcium signaling
Categories
Funding
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
- CAPES
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available