Low oxygen concentration
inside the tumor microenvironment represents
a major barrier for photodynamic therapy of many malignant tumors,
especially urothelial bladder cancer. In this context, titanium dioxide,
which has a low cost and can generate high ROS levels regardless of
local O
2
concentrations, could be a potential type of photosensitizer
for treating this type of cancer. However, the use of UV can be a
major disadvantage, since it promotes breakage of the chemical bonds
of the DNA molecule on normal tissues. In the present study, we focused
on the cytotoxic activities of a new material (Ti(OH)
4
)
capable of absorbing visible light and producing high amounts of ROS.
We used the malignant bladder cell line MB49 to evaluate the effects
of multiple concentrations of Ti(OH)
4
on the cytotoxicity,
proliferation, migration, and production of ROS. In addition, the
mechanisms of cell death were investigated using FACS, accumulation
of lysosomal acid vacuoles, caspase-3 activity, and mitochondrial
electrical potential assays. The results showed that exposure of Ti(OH)
4
to visible light stimulates the production of ROS and causes
dose-dependent necrosis in tumor cells. Also, Ti(OH)
4
was
capable of inhibiting the proliferation and migration of MB49 in low
concentrations. An increase in the mitochondrial membrane potential
associated with the accumulation of acid lysosomes and low caspase-3
activity suggests that type II cell death could be initiated by autophagic
dysfunction mechanisms associated with high ROS production. In conclusion,
the characteristics of Ti(OH)
4
make it a potential photosensitizer
against bladder cancer.