Photodynamic therapy (PDT) resistance by PARP1 regulation on PDT-induced apoptosis with autophagy in head and neck cancer cells.

BACKGROUND: Photodynamic therapy (PDT) is an anticancer treatment that generates excessive reactive oxygen species after photosensitizer treatments following specific wavelength irradiation. In another reports, PDT was regulated with autophagic cell death and apoptotic cell death. However, the mechanism of PDT resistance in PDT-stimulated cell death is unclear. In this study, we determined PDT resistance by autophagy and apoptosis in HP-PDT-treated oral cancer cells. MATERIALS &
METHODS: Cells were treated hematoporphyrin and then irradiation with or without inhibitor. Cell lysates were checked protein expression with specific antibody. PDT resistance cells were generated with PDT repeated treatments.
RESULTS: In HP-PDT, PDT induced autophagy through mTOR, ATG5, and LC3 in dose-dependent manners. Also, PDT at high dose induced apoptosis through caspase activation and PARP-1. Moreover, PARP-1 inhibitor protected cells against HP-PDT-induced cell death, but not by caspase inhibitor. At low dose of HP, autophagy inhibitor partially protected from HP-PDT-induced cell death. In autophagy phases, at low doses, HP-PDT regulated autophagic cell death through the inhibition of LC3II. Although autophagy inhibitor did not alter cell death directly, autophagy has associated with HP-PDT-induced apoptotic cell death by PARP-1 regulation.
CONCLUSION: Taken together, HP-PDT induces apoptotic cell death with autophagy in oral cancer cells. PDT resistance is related to autophagy by PARP-1 regulation in oral cancer cells.