Apoptotic effect of pheophorbide a-mediated photodynamic therapy on DMBA/TPA-induced mouse papillomas

Abstract

Pheophorbide a (Pa) is a chlorine-based photosensitizer, and Pa-mediated photodynamic therapy (PDT) reportedly exhibits antitumor activity against various malignancies. The aim of our study was to investigate the therapeutic effect of Pa-mediated PDT on 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorobol-13-acetate (TPA)-induced mouse papillomas. Thirty mice received a topical application of DMBA/TPA on their backs to induce mouse papillomas. One week after two sessions of Pa-mediated PDT, immunohistochemical stains and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay were performed to evaluate the apoptotic effects thereof on the papillomas. Among 63 mouse papillomas treated with Pa-mediated PDT, 17.5% of the lesions were completely removed 1 week after the first treatment, while 31.7% disappeared 1 week after the second treatment. Statistical analyses revealed significant differences in therapeutic outcomes for the Pa-mediated PDT group in comparison to a solvent-PDT group and a Pa group. Additionally, a marked downregulation of proliferating cell nuclear antigen expression, as well as upregulation of cleaved caspase 3 and cleaved poly(ADP-ribose) polymerase expression, was noted in the Pa-PDT group, compared to the solvent-PDT group and Pa group. TUNEL assay revealed higher apoptotic cell counts in the Pa-PDT group, although the difference was not statistically significant. Our data demonstrated that Pa-mediated PDT is effective in treating DMBA/TPA-induced mouse papillomas.