Data di Pubblicazione:
2008
Citazione:
Reversine selectively induces cell death in tumor cells / M. Piccoli, G. Palazzolo, N. Papini, L. Dileo, C. Sitzia, E. Conforti, G. Tettamanti, B. Venerando, L. Anastasia - In: 53rd National Meeting of the Italian Society of Biochemistry and Molecular Biology (SIB) and National Meeting of Chemistry of of Biological Systems Italian Chemical Society (SCI - Section CSB) : Palazzo dei Congressi di Riccione, 23rd-26th September 2008.Firenze : Firenze University Press, 2008 Sep. - ISBN 9788884538208. - pp. 16.11-16.11 (( Intervento presentato al 53. convegno National Meeting of the Italian Society of Biochemistry and Molecular Biology (SIB) and National Meeting of Chemistry of of Biological Systems Italian Chemical Society (SCI - Section CSB) tenutosi a Riccione nel 2008.
Abstract:
Reversine is a synthetic 2,6-distribuited purine1, which
has been shown to increase cell plasticity with the ability
to reprogram lineage-committed cells to a more primitive
multipotent state. In particular, reversine-treated dermal
fibroblasts could be then induced to differentiate to
skeletal muscle both in vitro and in vivo2. Nevertheless,
reversine mechanism of action is still not fully
demonstrated, although it has been shown that the
molecule inhibits MEK1, nonmuscle myosin II heavy
chain3, and aurora kinases. Although it is still unclear if
these effects are strictly related to de-differentiation, it is
now quite clear that the molecule inhibits cell growth.
Thus, it has been already reported that reversine inhibits
cell growth and colony formation in tumor cells.
Surprisingly and remarkably, in our hands, treatment of
several types of cancer cells (including neuroblastoma,
fibrosarcoma, and glioblastoma cancer stem cells) with
reversine at micromolar concentration, not only inhibited
tumor cells growth, but extensively induced cell death.
On the other hand, we did not observe the same lethal
effects on normal cells (including human and murine
primary dermal fibroblast, murine myoblasts, rat and
human mesenchymal stem cells, and murine
mesangioblasts), but only a reversible cell growth arrest.
Moreover, we found that tumor cells seem to undergo
different death pathways. In fact, while neuroblastoma
SK-N-BE cells revealed all the canonical signs of
apoptosis (chromatin condensation, caspase 3
activation), we could not find the same evidences in
fibrosarcoma cells HT1080. Nevertheless, cell cycle
analysis and morphological features, after reversine
treatment, seem to point out that cell death may be due to
mitotic catastrophe, which may be caspase dependent or
independent. In fact, reversine treatment leads to the
formation of large cells with several micronuclei, possibly
due to the aberrant chromosome segregation and the
inhibition of cytokinesis. Reversine inhibition of aurora
kinase and nonmuscle myosin II heavy chain, which hold
crucial roles in the correct mitotic division, may result in
the observed effects. Cell cycle analysis shows that
reversine induces endoreplication, but while normal cells
can control this effect and block cells in G1 phase, tumor
cells, where G1 checkpoint is de-regulated, keep cycling
to a point where micronucleated polyploid populations start to die.
Tipologia IRIS:
03 - Contributo in volume
Elenco autori:
M. Piccoli, G. Palazzolo, N. Papini, L. Dileo, C. Sitzia, E. Conforti, G. Tettamanti, B. Venerando, L. Anastasia
Link alla scheda completa:
Titolo del libro:
53rd National Meeting of the Italian Society of Biochemistry and Molecular Biology (SIB) and National Meeting of Chemistry of of Biological Systems Italian Chemical Society (SCI - Section CSB) : Palazzo dei Congressi di Riccione, 23rd-26th September 2008.