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

Abstract

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.

• Authors: Jisun Kim, Wonbong Lim, Sangwoo Kim, Sangmi Jeon, Zheng Hui, Kou Ni, Changsu Kim, Yeonggwan Im, Hongran Choi, Okjoon Kim
• Journal: Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology (J Oral Pathol Med) Vol. 43 Issue 9 Pg. 675-84 (Oct 2014) ISSN: 1600-0714 [Electronic] Denmark
• PMID: 24931630 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chemical References

• ATG5 protein, human
• Autophagy-Related Protein 5
• Caspase Inhibitors
• Hematoporphyrins
• MAP1LC3A protein, human
• Microtubule-Associated Proteins
• Photosensitizing Agents
• Poly(ADP-ribose) Polymerase Inhibitors
• PARP1 protein, human
• Poly (ADP-Ribose) Polymerase-1
• Poly(ADP-ribose) Polymerases
• MTOR protein, human
• TOR Serine-Threonine Kinases
• CASP3 protein, human
• CASP8 protein, human
• Caspase 3
• Caspase 8

Topics

• Apoptosis (drug effects)
• Autophagy (drug effects)
• Autophagy-Related Protein 5
• Caspase 3 (drug effects)
• Caspase 8 (drug effects)
• Caspase Inhibitors (pharmacology)
• Cell Death (drug effects)
• Cell Line, Tumor
• Enzyme Activation (drug effects)
• Head and Neck Neoplasms (drug therapy, pathology)
• Hematoporphyrins (therapeutic use)
• Humans
• Microtubule-Associated Proteins (antagonists & inhibitors, drug effects)
• Photochemotherapy
• Photosensitizing Agents (therapeutic use)
• Poly (ADP-Ribose) Polymerase-1
• Poly(ADP-ribose) Polymerase Inhibitors
• Poly(ADP-ribose) Polymerases (drug effects)
• TOR Serine-Threonine Kinases (drug effects)