Abstract |
Phosphoethanolamine (Pho-s) is a compound involved in phospholipid turnover, acting as a substrate for many phospholipids of the cell membranes. In a recent study, we showed that Pho-s has antitumor effect in the several tumor cells. In this study we evaluated the antitumor activity of synthetic Pho-s on MCF-7 breast cancer cells. Here we demonstrate that Pho-s is cytotoxic to MCF-7 cells in a dose-dependent manner, while it is cytotoxic to MCF10 only at higher concentrations. In addition, Pho-s induces a disruption in mitochondrial membrane potential (Δψm). Furthermore, Pho-s induces mitochondria aggregates in the cytoplasm and DNA fragmentation of MCF-7 cells visualized by confocal microscopy. In agreement with the reduction on Δψm, we showed that Pho-s induces apoptosis followed by an increase in cytochrome c expression and capase-3-like activity in MCF-7 cells. Our results demonstrate that Pho-s induces a cell cycle arrest in the G1 phase through an inhibition of cyclin D1 and stimulates p53. An additional highlight of this study is the finding that Pho-s inhibits Bcl-2, inducing apoptosis through the mitochondrial pathway. Taken together, these results show that Pho-s is a promising compound in the fight against cancer.
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Authors | Adilson Kleber Ferreira, Renato Meneguelo, Alexandre Pereira, Otaviano Mendonça R Filho, Gilberto Orivaldo Chierice, Durvanei Augusto Maria |
Journal | Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
(Biomed Pharmacother)
Vol. 67
Issue 6
Pg. 481-7
(Jul 2013)
ISSN: 1950-6007 [Electronic] France |
PMID | 23773853
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2013 Elsevier Masson SAS. All rights reserved. |
Chemical References |
- Antineoplastic Agents
- Ethanolamines
- Proto-Oncogene Proteins c-bcl-2
- TP53 protein, human
- Tumor Suppressor Protein p53
- Cyclin D1
- phosphorylethanolamine
- Cytochromes c
- Caspase 3
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Topics |
- Antineoplastic Agents
(pharmacology)
- Apoptosis
(drug effects, genetics)
- Breast Neoplasms
(drug therapy, genetics, metabolism)
- Caspase 3
(genetics, metabolism)
- Cell Cycle Checkpoints
(drug effects, genetics)
- Cell Death
(drug effects, genetics)
- Cell Line, Tumor
- Cyclin D1
(genetics, metabolism)
- Cytochromes c
(genetics, metabolism)
- Cytoplasm
(drug effects, genetics, metabolism)
- DNA Fragmentation
(drug effects)
- Ethanolamines
(pharmacology)
- Female
- G1 Phase
(drug effects, genetics)
- Humans
- MCF-7 Cells
- Membrane Potential, Mitochondrial
(drug effects, genetics)
- Mitochondria
(drug effects, genetics, metabolism)
- Proto-Oncogene Proteins c-bcl-2
(genetics, metabolism)
- Signal Transduction
(drug effects, genetics)
- Tumor Suppressor Protein p53
(genetics, metabolism)
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