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analysis of APE1, C99A, C138A, and C99A/C138A
substituted proteins. In this regard, 8-51 behaves more
similarly to E3330 than the other two compounds.
Each of the compounds was also tested in Matrigel
and TUNEL assays. The naphthoquinone compounds
had up to six-fold greater activity as compared to
E3330 in inhibiting endothelial tube growth of ECFCs,
indicating anti-angiogenesis activity. Both E3330 and 8-
51 decreased the growth of SKOV-3X and Hey-C2
ovarian cancer cell lines through growth inhibition,
whereas RN10-52 modestly induced apoptosis and
RN7-60 induced a dramatic apoptotic effect. Thus, based
on studies to date, 8-51 appears to be the most promising
of this series of compounds. 163 These and other studies
suggest that specific inhibition of APE1's redox activity
in cancer cells arrests cell growth but does not induce
apoptosis. Thus, collectively, studies reported to date
suggest that APE1 redox function is a promising new
target for cancer therapeutic development.
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