INVESTIGADORES
COCCA Claudia Marcela
artículos
Título:
15-Deoxi-Delta(12,14)-prostaglandin J(2) is a tubulin-binding agent that destabilizes microtubules and induces mitotic arrest
Autor/es:
CLAUDIA COCCA; JORGE DORADO; ENRIQUE CALVO; JUAN ANTONIO LÓPEZ; ANGEL SANTOS; ANA PEREZ-CASTILLO
Revista:
BIOCHEMICAL PHARMACOLOGY
Editorial:
PERGAMON-ELSEVIER SCIENCE LTD
Referencias:
Año: 2009 vol. 78 p. 1330 - 1339
ISSN:
0006-2952
Resumen:
15-Deoxi-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) is known to play
an important role in the pathophysiology of carcinogenesis, however,
the molecular mechanisms underlying these effects are not yet fully
understood. Recently, we have shown that 15d-PGJ(2) is a potent inducer
of breast cancer cell death and that this effect is associated with a
disruption of the microtubule cytoskeletal network. Here, we show that
treatment of the MCF-7 breast cancer cell line with 15d-PGJ(2) induces
an accumulation of cells in the G(2)/M compartment of the cell cycle
and a marked disruption of the microtubule network. 15d-PGJ(2)
treatment causes mitotic abnormalities that consist of failure to form
a stable metaphase plate, incapacity to progress through anaphase, and
failure to complete cytokinesis. 15d-PGJ(2) binds to tubulin through
the formation of a covalent adduct with at least four cysteine residues
in alpha- and beta-tubulin, as detected by hybrid triple-quadrupole
mass spectrometry analysis. Overall, these results support the
hypothesis that microtubule disruption and mitotic arrest, as a
consequence of the binding of 15d-PGJ(2) to tubulin, can represent one
important pathway leading to breast cancer cell death.