Abstract
A combination of demethylating agents and histone
deacetylase inhibitors (HDACi) has been proposed as a novel
therapy in leukemia and myelodysplasia. In HL-60 cells
azacytidine (AZA) and Metacept-1 (MCT-1), a novel HDACi
augmented inhibition of cell growth and increased apoptosis.
In identifying a molecular mechanism responsible for these
effects MCT-1 alone and in combination with AZA induced
p15INK4b, p21WAF1/CIP1 and Caspase-3 whilst attenuating Bcl-
XL expression. Interestingly, MCT-1 in combination with
AZA significantly induced the recently identified suppressor
of leukemogenesis Nur77 and attenuated AZA-induced
MMP-9 expression. The combination of MCT-1 and AZA is
more effective in inhibiting leukemic cell growth and
induction of apoptosis. Regulation of a recently identified
tumour suppressor gene together with cell cycle, apoptosis and
matrix degrading proteases may underpin the molecular
mechanism responsible for these effects.
Lingua originale | English |
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pagine (da-a) | 573-579 |
Numero di pagine | 7 |
Rivista | International Journal of Oncology |
Volume | 34 |
Stato di pubblicazione | Pubblicato - 2009 |
Pubblicato esternamente | Sì |
Keywords
- decitabine
- histone deacetylase