2.4.2 Reactive oxygen species (ROS)
Sudjit Luanpitpong et al 63 first confirmed a
subpopulation of CSC (cancer stem cells) that was regulated by using ROS
(reactive oxygen species) in MCL cell lines and patient-derived primary
cells and inversely correlated with the sensitivity of bortezomib (BTZ).
ROS are necessary signaling molecules in the tumor microenvironment. O2-
has a vast inhibitory impact on CSC-like cells, while H2O2 has an
extensive enriching and apoptosis-inhibiting impact on CSC-like cells.
Mcl-1 and Zeb-1 (also regarded as TCF8) are effective targets of O2- and
H2O2. Using CRISPR/Cas9 gene editing technology, the expression of Mcl-1
was inhibited, and the expression of Zeb-1 was decreased, while the
expression of TCF8 was increased. It was found that intracellular ROS
levels increased significantly after Mcl-1 gene silencing, and Mcl-1 is
a critical target gene of O2 and has a regulatory role in CSC-like
cells, suggesting that ROS has an impact in BTZ-induced apoptosis and
CSC-like cells can resist BTZ-induced apoptosis by apoptosis-regulating
protein Mcl-1. What’s more, mitochondrial membrane potential is also an
important factor in the protective impact of the mitochondrial
antioxidant system on BTZ-induced apoptosis.