15-deoxi-delta(12,14)-prostaglandinJ2 is a tubulin-binding agent that desestabilizes microtubules and induces G2/M arrest.

C. COCCA; J. DORADO; E. CASTRO; J. A. LÓPEZ; A. SANTOS; A. PÉREZ-CASTILLO

Las Palmas, Islas Canarias. España

Congreso; XI Reunión de la Asociación Española Investigación del Cáncer (ASEICA); 2007

15deoxiΔ12,14prostaglandinJ2 (15dPGJ2) plays a main role in carcinogenesis. 15dPGJ2, a ligand for peroxisome proliferators-activated receptor gamma (PPARg), is now thought to exert its effects through PPARg-dependent and –independent mechanisms. We have shown that 15dPGJ2 is a potent inducer of breast cancer cell death and provokes a disruption of the microtubule cytoskeletal network. Here, we show that 15dPGJ2 induces an accumulation of cells in the G2/M compartment and a marked disruption of the microtubule network in MCF7 cells. We also show that 15dPGJ2 causes mitotic abnormalities such as failure to form a stable metaphase plate, incapacity to progress through anaphase, and uncompleted cytokinesis. These effects are associated with a loss of expression of microtubule nucleating proteins gamma-tubulin and pericentrin. Immunoprecipitation, confocal studies and mass sprectrometry show that 15dPGJ2 binds four cysteine residues of alpha- and beta-subunits in polymerized tubulin. These results support the hypothesis that microtubule disruption and mitotic arrest following the binding of 15dPGJ2 to tubulin, can represent one important pathway leading to breast cancer cell death.