Academic Journal
15-Deoxy-{Delta}-12,14-prostaglandin J2 induces programmed cell death of breast cancer cells by a pleiotropic mechanism
| العنوان: | 15-Deoxy-{Delta}-12,14-prostaglandin J2 induces programmed cell death of breast cancer cells by a pleiotropic mechanism |
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| المؤلفون: | Pignatelli, Miguel, Sánchez-Rodríguez, Jinny, Santos, Angel, Perez-Castillo, Ana |
| بيانات النشر: | Oxford University Press |
| سنة النشر: | 2005 |
| المجموعة: | HighWire Press (Stanford University) |
| مصطلحات موضوعية: | CANCER BIOLOGY |
| الوصف: | Activation of peroxisome proliferator-activated receptor γ (PPARγ) has been found to induce cell death in a variety of cells. In this regard, we reported recently that 15-deoxy-Δ-12,14-prostaglandin J 2 (15dPG-J 2 ), a specific ligand of the nuclear receptor PPARγ, inhibits proliferation and induces cellular differentiation and apoptosis in the breast cancer cell line MCF-7. In addition to PPARγ activation other proteins, such as NF-κB and AP1, have been shown to be targets of 15dPG-J 2 . However, the mechanism by which 15dPG-J 2 triggers cell death is still elusive. Our results demonstrate that 15dPG-J 2 initiates breast cancer cell death via a very rapid and severe impairment of mitochondrial function, as revealed by a drop in mitochondrial membrane potential (ΔΨ m ), generation of reactive oxygen species (ROS) and a decrease in oxygen consumption. In addition, 15dPG-J 2 can also activate an intrinsic apoptotic pathway involving phosphatidyl serine externalization, caspase activation and cytochrome c release. Bcl-2 over-expression and zVADfmk, albeit preventing caspase activation, have no effect on 15dPG-J 2 -mediated mytochondrial dysfunction and loss of cell viability. In contrast, the addition of radical scavengers or rotenone, which prevent 15dPG-J 2 -induced ROS production, block the loss of cell viability induced by this prostaglandin. Finally, 15dPG-J 2 -induced cell death appears to involve disruption of the microtubule cytoskeletal network. Together, these results suggest that PG-J2-induced mitochondrial dysfunction and ROS production inevitably leads to death, with or without caspases. |
| نوع الوثيقة: | text |
| وصف الملف: | text/html |
| اللغة: | English |
| Relation: | http://carcin.oxfordjournals.org/cgi/content/short/26/1/81; http://dx.doi.org/10.1093/carcin/bgh308 |
| DOI: | 10.1093/carcin/bgh308 |
| الاتاحة: | http://carcin.oxfordjournals.org/cgi/content/short/26/1/81 https://doi.org/10.1093/carcin/bgh308 |
| Rights: | Copyright (C) 2005, Oxford University Press |
| رقم الانضمام: | edsbas.D61DAABA |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/carcin/bgh308 |
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