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

Abstract

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.

• Authors: Mee Young Ahn, Hyo-Eun Yoon, Seong-Min Kwon, Jun Lee, Seung-Ki Min, Yong-Chul Kim, Sang-Gun Ahn, Jung-Hoon Yoon
• 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. 42 Issue 1 Pg. 17-25 (Jan 2013) ISSN: 1600-0714 [Electronic] Denmark
• PMID: 22742535 (Publication Type: Journal Article)
• Copyright: © 2012 John Wiley & Sons A/S.

Chemical References

• MAP1LC3B protein, human
• Microtubule-Associated Proteins
• Photosensitizing Agents
• Reactive Oxygen Species
• Chlorophyll
• pheophorbide a

Topics

• Apoptosis
• Autophagy (drug effects)
• Carcinoma, Squamous Cell (drug therapy)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Chlorophyll (analogs & derivatives, chemical synthesis, pharmacology, therapeutic use)
• Humans
• MAP Kinase Signaling System (drug effects)
• Microtubule-Associated Proteins (biosynthesis)
• Mouth Neoplasms (drug therapy)
• Necrosis
• Phagosomes
• Photochemotherapy
• Photosensitizing Agents (chemical synthesis, pharmacology, therapeutic use)
• Reactive Oxygen Species (metabolism)