Format

Send to

Choose Destination
See comment in PubMed Commons below
Leuk Res. 2010 Jan;34(1):77-84. doi: 10.1016/j.leukres.2009.09.005. Epub 2009 Sep 27.

Protein kinase A activators and the pan-PPAR agonist tetradecylthioacetic acid elicit synergistic anti-leukaemic effects in AML through CREB.

Author information

1
Institute of Medicine, Haematology Section, University of Bergen, Bergen, Norway.

Abstract

Targeting of signal transduction pathways and transcriptional regulation represents an attractive approach for less toxic anti-leukaemic therapy. We combined protein kinase A (PKA) activation with a pan-peroxisome proliferator-activated receptor (PPAR) activator tetradecylthioacetic acid, resulting in synergistic decrease in viability of AML cell lines. PKA isoform II activation appeared to be involved in inhibition of proliferation but not induction of apoptosis in HL-60 cells. Inhibition of CREB function protected against this anti-leukaemic effect with higher efficiency than enforced Bcl-2 expression. Preclinical studies employing the rat AML model Brown Norwegian Myeloid Leukaemia also indicated anti-leukaemic activity of the combination therapy in vivo. In conclusion, combined PKA and pan-PPAR activation should be explored further to determine its therapeutic potential.

PMID:
19786302
DOI:
10.1016/j.leukres.2009.09.005
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center