Preclinical validation of talaporfin sodium-mediated photodynamic therapy for esophageal squamous cell carcinoma.

Abstract

Photodynamic therapy (PDT) kills cancer cells via a photochemical reaction mediated by an oncotropic photosensitizer. Herein, we performed an experimental preclinical study to validate the anti-tumour effect of talaporfin sodium-mediated PDT (t-PDT) for esophageal squamous cell carcinoma (ESCC) cells. We used human ESCC cells derived from various differentiation grades or resistant to 5-fluorouracil (5-FU). The cytotoxic effect of t-PDT was determined by evaluating cell viability, apoptosis and generation of reactive oxygen species (ROS) and DNA double-strand breaks. Furthermore, the anti-tumour effect of t-PDT was assessed using an anchorage-independent cell-growth assay and xenograft transplantation models. t-PDT induced potent cytotoxicity in ESCC cells independent of their differentiation grade or 5-FU resistance. Moreover, t-PDT induced robust apoptosis, as indicated by cell shrinkage, perinuclear vacuolization, nuclear fragmentation and induction of annexin V-positive cells. This apoptotic response was accompanied by concurrent activation of ROS, and induction of DNA double-strand breakage. Importantly, t-PDT suppressed efficiently anchorage-independent cell growth as well as ESCC-xenografted tumor formation. In aggregate, t-PDT showed anti-tumor potential for ESCC cells with various histological grades or chemoresistance, providing a novel translational rationale of t-PDT for the treatment of ESCC.

• Authors: Shinya Ohashi, Osamu Kikuchi, Mihoko Tsurumaki, Yukie Nakai, Hiroi Kasai, Takahiro Horimatsu, Shin'ichi Miyamoto, Akira Shimizu, Tsutomu Chiba, Manabu Muto
• Journal: PloS one (PLoS One) Vol. 9 Issue 8 Pg. e103126 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 25090101 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Porphyrins
• Reactive Oxygen Species
• Talaporfin

Topics

• Animals
• Apoptosis (drug effects)
• Carcinoma, Squamous Cell (drug therapy, pathology)
• Cell Adhesion (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• DNA Breaks, Double-Stranded (drug effects)
• Esophageal Neoplasms (drug therapy, pathology)
• Esophageal Squamous Cell Carcinoma
• Fluorescence
• Humans
• Intracellular Space (drug effects, metabolism)
• Mice
• Photochemotherapy
• Porphyrins (pharmacology, therapeutic use)
• Reactive Oxygen Species (metabolism)
• Reproducibility of Results