G2/M cell-cycle arrest and apoptosis by n-3 fatty acids in a pancreatic cancer model |
| |
Authors: | Dekoj Thomas Lee Sang Desai Sagun Trevino Jose Babcock Tricia A Helton W Scott Espat N Joseph |
| |
Affiliation: | Department of Surgery, University of Illinois at Chicago, Chicago, Illinois 60612, USA. |
| |
Abstract: | BACKGROUND: n-3 fatty acids (n-3FA) have anti-inflammatory and anti-proliferative effects including modulation of pro-inflammatory cascade mediators and cytokine elaboration (i.e., TNF-alpha, IL-10 and PGE(2)) in many cell lines. However, mechanisms of anti-proliferative effects have not been clearly defined. MATERIALS AND METHODS: MIA PaCa-2 pancreatic cancer cells were treated either with n-3FA (treatment), media (control), or n-6FA (control) for all experiments. Cellular proliferation was evaluated with WST-1 reagent. Cells were stained with propidium iodide and analyzed by flow cytometry for cell-cycle arrest, which was further analyzed by cdc2 expression. Membrane and media lipid concentrations were analyzed by high-performance liquid chromatography. Apoptosis was evaluated by AnnexinV-FITC flow cytometry and reconfirmed by poly (ADP-ribose) polymerase (PARP) cleavage and B(cl)-2 expression. RESULTS: Propidium iodide flow cytometry of MIA PaCa-2 dosed with n-3FA showed a decrease in cells in G1 phase (11-17%) and an increase cells in G2 phase (7-13%) from controls. cdc2 expression was also decreased at 24 h compared to controls. Annexin-V staining of n-3FA-treated cells demonstrated time-dependent increased apoptosis and PARP cleavage was present only in the n-3FA treatment group. Phospho-B(cl)-2 was also decreased in the n-3FA-treated cells compared to controls. CONCLUSIONS: Co-incubation of MIA PaCa-2 cells with n-3FA results in both dose- and time-dependent cell-cycle arrest. Cells also progress to cell death via apoptosis. These data support the potential applicability for n-3FA as an antiproliferative and pro-apoptotic strategy. |
| |
Keywords: | fish oil omega-3 n-3 MIA PaCa-2 pancreatic adenocarcinoma inflammation cell cycle apoptosis G2/M |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|