p53 family members — important messengers in cell death signaling in photodynamic therapy of cancer?

Abstract

TP53 is one of the genes most frequently inactivated in cancers. Mutations in TP53 gene are linked to worse prognosis and shorter overall survival of cancer patients. TP53 encodes a critical tumor suppressor, which dictates cell fate decisions upon stress stimuli. As a sensor of cellular stress, p53 is a relevant messenger of cell death signaling in ROS-driven photodynamic therapy (PDT) of cancer. The significant role of p53 in response to PDT has been reported for several clinically approved photosensitizers. Multiple reports described that wild-type p53 contributes to cell killing upon photodynamic therapy with clinically approved photosensitizers but the mechanism is still not fully understood. This work outlines the diverse functions of p53 family members in cancer cells' susceptibility and resistance to PDT. In summary p53 and p53 family members are emerging as important mediators of cell death signaling in photodynamic therapy of cancer, however the mechanism of cell death provoked during PDT might differ depending on the tissue type and the photosensitizer applied.

The Effect of Phototherapy on Cancer Predisposition Genes of Diabetic and Normal Human Skin Fibroblasts

“…Eventually, either more abnormal cells would be produced or more apoptosis could occur. These hypotheses are supported by previous studies from Płonka et al [4] and Acedo and Zawacka-Pankau [5]. These studies found that the expression of the P53 (also called TP53) gene was lower after phototherapy, which led to the initiation of the apoptosis process.…”

The p53/MDM2/MDMX-targeted therapies—a clinical synopsis

“…In ALA-PDT, PpIX is next excited with the light of a wavelength matching the absorption maximum of the compound (λ = 410 nm) with 10 J/cm 2 light dose per treatment. PpIX excitation leads to the accumulation of reactive oxygen species (ROS) and cell death 4 . Interestingly, the outcome of ALA-PDT can be improved by the pretreatment with 5-fluorouracyl (5-FU) because it induces wt-p53, thus predisposes to stress-induced apoptosis.…”

Effects of Visible‐Light Irradiation of Protoporphyrin IX on the Self‐Assembly of Tubulin Heterodimers

“…The generation of 1 O 2 appears to be involved in the mechanisms, however, chemical changes were not characterized and the role of PPIX radicals generated by electron transfer cannot be entirely ruled out. Although PPIX is hypothesized to target other proteins in cells (e.g., p53 [35] ), demonstrating that protein target can be modified through photosensitized mechanisms may open the possibility of modified application of porphyrin photosensitizers in biomedical applications.…”