Photodynamic Therapy (
PDT) involves the administration of a
tumor localizing
photosensitizing agent, which upon activation with light of an appropriate wavelength leads to the destruction of the
tumor cells. The aim of the present study was to determine the efficacy of
erythrosine as a
photosensitizer for the
PDT of oral
malignancies. The
drug uptake kinetics of
erythrosine in malignant (H357) and pre-malignant (DOK) oral epithelial cells and their susceptibility to
erythrosine-based
PDT was studied along with the determination of the subcellular localization of
erythrosine. This was followed by initial investigations into the mechanism of cell killing induced following
PDT involving both high and low concentrations of
erythrosine. The results showed that at 37 °C the uptake of
erythrosine by both DOK and H357 cells increased in an
erythrosine dose dependent manner. However, the percentage of cell killing observed following
PDT differed between the 2 cell lines; a maximum of ~80% of DOK cell killing was achieved as compared to ~60% killing for H357 cells. Both the DOK and H357 cell types exhibited predominantly mitochondrial accumulation of
erythrosine, but the mitochondrial trans-membrane potential (ΔΨ(m)) studies showed that the H357 cells were far more resistant to the changes in ΔΨ(m) when compared to the DOK cells and this might be
a factor in the apparent relative resistance of the H357 cells to
PDT. Finally, cell death morphology and
caspase activity analysis studies demonstrated the occurrence of extensive
necrosis with high dose
PDT in DOK cells, whereas apoptosis was observed at lower doses of
PDT for both cell lines. For H357 cells, high dose
PDT produced both apoptotic as well as necrotic responses. This is the first instance of
erythrosine-based
PDT's usage for
cancer cell killing.