title: Synthetic phosphoethanolamine induces cell cycle arrest and apoptosis in human breast cancer MCF-7 cells through the mitochondrial pathway.
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.
authors.affiliation: Biochemistry and Biophysical Laboratory, Butantan Institute, Sao Paulo, Brazil.
authors.forename: Adilson Kleber
authors.initials: AK
authors.lastname: Ferreira
authors.forename: Renato
authors.initials: R
authors.lastname: Meneguelo
authors.forename: Alexandre
authors.initials: A
authors.lastname: Pereira
authors.forename: Otaviano Mendonça R
authors.initials: OM
authors.lastname: Filho
authors.forename: Gilberto Orivaldo
authors.initials: GO
authors.lastname: Chierice
authors.forename: Durvanei Augusto
authors.initials: DA
authors.lastname: Maria
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects* / Q000235:genetics; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D045304:Cytochromes c / Q000235:genetics / Q000378:metabolism; D003593:Cytoplasm / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D004983:Ethanolamines / Q000494:pharmacology*; D005260:Female; D016193:G1 Phase / Q000187:drug effects / Q000235:genetics; D006801:Humans; D061986:MCF-7 Cells; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000235:genetics; D008928:Mitochondria / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D004983:Ethanolamines; D019253:Proto-Oncogene Proteins c-bcl-2; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1; C005448:phosphorylethanolamine; D045304:Cytochromes c; D053148:Caspase 3
keywords: Apoptosis; Caspase-3-like; MCF-7 breast cancer; Mitochondria; Synthetic phosphoethanolamine