INVESTIGADORES
MUNARRIZ Eliana Rosa
artículos
Título:
Desmethylclomipramine induces the accumulation of autophagy markers by blocking autophagic flux.
Autor/es:
ROSSI M, MUNARRIZ ER, BARTESAGHI S, MILANESE M, DINSDALE D, GUERRA-MARTIN MA, BAMPTON ET, GLYNN P, BONANNO G, KNIGHT RA, NICOTERA P, MELINO G.
Revista:
JOURNAL OF CELL SCIENCE
Editorial:
COMPANY OF BIOLOGISTS LTD
Referencias:
Año: 2009 p. 3330 - 3339
ISSN:
0021-9533
Resumen:
Alterations in the autophagic pathway are associated with the onset and
progression of various diseases. However, despite the therapeutic
potential for pharmacological modulators of autophagic flux, few such
compounds have been characterised. Here we show that clomipramine, an
FDA-approved drug long used for the treatment of psychiatric disorders,
and its active metabolite desmethylclomipramine (DCMI) interfere with
autophagic flux. Treating cells with DCMI caused a significant and
specific increase in autophagosomal markers and a concomitant blockage
of the degradation of autophagic cargo. This observation might be
relevant in therapy in which malignant cells exploit autophagy to
survive stress conditions, rendering them more susceptible to the action
of cytotoxic agents. In accordance, DCMI-mediated obstruction of
autophagic flux increased the cytotoxic effect of chemotherapeutic
agents. Collectively, our studies describe a new function of DCMI that
can be exploited for the treatment of pathological conditions in which
manipulation of autophagic flux is thought to be beneficial.