Biomedical Engineering Reference
In-Depth Information
with ischemia, PARP 1 hyperactivation results in depletion of NAD+
and ATP, resulting in cell death by necrosis or apoptosis [48].
Figure 15.2
(a) Structure of PARP. (b) Activity of PARP.
Reprinted by
permission from Macmillan Publishers Ltd:
Nature Reviews
Cancer
, Rouleau M, PARP Inhibition: PARP1 and Beyond,
copyright 2010.
PARP 1 also activates the stress-inducible transcription complex
NF-
κ
B,
which
inhibits
apoptosis
and
promotes
proliferation.
κ
Cancers demonstrate increased expression of NF-
B. The complex is
constitutively activated in some breast cancers, particularly in those
that are hormone refractory and those with worse prognoses. NF-
κ
B
κ
correlates with progression of disease in breast cancer. NF-
B is also
activated by XRT and chemotherapy. Inhibition of NF-
B sensitizes
cells to XRT and chemotherapy [55]. In addition, PARP 1 has some
κ
