The effect of MTH1 inhibition on cancer cell survival has been elusive. Here we report that
although silencing of MTH1 does not affect survival of melanoma cells, TH588, one of the
first-in-class MTH1 inhibitors, kills melanoma cells through apoptosis independently of its
inhibitory effect on MTH1. Induction of apoptosis by TH588 was not alleviated by MTH1
overexpression or introduction of the bacterial homolog of MTH1 that has 8-oxodGTPase
activity but cannot be inhibited by TH588, indicating that MTH1 inhibition is not the cause of …

Cancer cells commonly contain elevated levels of reactive oxygen species (ROS) resulting
from oncogenic stimulation. On one hand, ROS promote cancer cell survival, proliferation,
and metastasis. On the other, high levels of ROS suppress tumour growth through inhibition
of proliferation and induction of apoptosis and senescence via damage to DNA.
Incorporation of oxidized dNTPs such as 8-oxo-deoxy-guanine (8-oxo-dGTP) and 2-OH-
deoxy-adenosine (2-OH-dATP) into genomic DNA plays an important role in apoptosis …