Synthesized Pheophorbide a-mediated photodynamic therapy induced apoptosis and autophagy in human oral squamous carcinoma cells

• Published in: Journal of oral pathology & medicine 2013-01, Vol.42 (1), p.17-25
• Main Authors: Ahn, Mee Young, Yoon, Hyo-Eun, Kwon, Seong-Min, Lee, Jun, Min, Seung-Ki, Kim, Yong-Chul, Ahn, Sang-Gun, Yoon, Jung-Hoon
• Format: Article
• Language: English
• Subjects: Apoptosis; autophagy; Autophagy - drug effects; Biological and medical sciences; Carcinoma, Squamous Cell - drug therapy; Cell Line, Tumor; Cell Proliferation - drug effects; Chlorophyll - analogs & derivatives; Chlorophyll - chemical synthesis; Chlorophyll - pharmacology; Chlorophyll - therapeutic use; Dentistry; Humans; MAP Kinase Signaling System - drug effects; Medical sciences; Microtubule-Associated Proteins - biosynthesis; Mouth Neoplasms - drug therapy; Necrosis; oral sqaumous cell carcinoma; Otorhinolaryngology. Stomatology; Phagosomes; Photochemotherapy; Photosensitizing Agents - chemical synthesis; Photosensitizing Agents - pharmacology; Photosensitizing Agents - therapeutic use; Reactive Oxygen Species - metabolism; synthesized Pa-PDT; Tumors; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology
• ISSN: 0904-2512; 1600-0714
• DOI: 10.1111/j.1600-0714.2012.01187.x

Background:  Pheophorbide a (Pa) is a chlorine‐based photosensitizer derived from an ethnopharmacological herb, and our group recently synthesized Pa by the removal of a magnesium ion and a phytyl group from chlorophyll‐a. In this study, the effect of photodynamic therapy (PDT) with synthesized Pa was examined in a human oral squamous cell carcinoma (OSCC) cells. Methods:  Cells were treated with PDT with Pa, and reactive oxygen species (ROS) and mitochondrial membrane potential [ΔΨ (m)] were examined. Apoptosis was measured using annexin V staining and immunoblot. Autophagy was characterized by the increase in LC3B‐II and the formation of autophagosome and acidic vesicular organelles (AVOs). Results:  Pa‐PDT inhibited the proliferation of OSCC cells in a dose‐dependent manner. Pa‐PDT increased the number of apoptotic cells by inactivating ERK pathway. Pa‐PDT also induced autophagy in OSCC cells evidenced by the increased levels of LC3 type II expression and the accumulation of AVOs. The inhibition of autophagy enhanced Pa‐PDT‐mediated cytotoxicity through an increase in necrosis. Conclusions:  These results suggest that synthesized Pa‐PDT exerts anti‐tumor effects by inducing apoptosis and autophagy and provide novel evidence that Pa‐PDT induces autophagy, and autophagy inhibition enhances Pa‐PDT‐mediated necrosis in OSCC cells.