A new naturally derived photosensitizer and its phototoxicity on head and neck cancer cells.

Abstract

In our screening for photosensitizers from natural resources, 15(1)-hydroxypurpurin-7-lactone ethyl methyl diester (compound 1) was isolated for the first time from an Araceae plant. To evaluate the efficacy of compound 1 as a photosensitizer for head and neck cancers, compound 1 was studied in reference to a known photosensitizer pheophorbide-a (Pha), in terms of photophysical properties, singlet oxygen generation and in in vitro experiments (intracellular uptake and phototoxicity assays) in two oral (HSC2 and HSC3) and two nasopharyngeal (HK1 and C666-1) cancer cell lines. In this study, compound 1 exhibited higher intracellular uptake over 24 h compared with Pha in both HSC3 and HK1 cells. When activated by ≥4.8 J cm(-2) of light, compound 1 was slightly more potent as a photosensitizer than Pha by consistently having marginally lower IC(50) values across different cell lines. In flow cytometry experiments to study the mechanism of photoactivated cell death in HSC3, compound 1 was observed to induce more pronounced apoptosis compared with Pha, which may have been driven by the transient G(2)/M cell cycle block which was also observed. These promising results on compound 1 warrant its further investigation as a clinically useful photodynamic therapy agent for head and neck cancer.

• Authors: Siang Hui Lim, Hong Boon Lee, Anthony Siong Hock Ho
• Journal: Photochemistry and photobiology (Photochem Photobiol) 2011 Sep-Oct Vol. 87 Issue 5 Pg. 1152-8 ISSN: 1751-1097 [Electronic] United States
• PMID: 21534974 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 The Authors. Photochemistry and Photobiology © 2011 The American Society of Photobiology.

Chemical References

• Esters
• Lactones
• Photosensitizing Agents
• Plant Extracts
• Chlorophyll
• Singlet Oxygen
• pheophorbide a

Topics

• Apoptosis (drug effects, radiation effects)
• Araceae (chemistry)
• Cell Cycle (drug effects, radiation effects)
• Cell Line, Tumor
• Cell Survival (drug effects, radiation effects)
• Chlorophyll (analogs & derivatives, pharmacology)
• Dose-Response Relationship, Drug
• Esters (chemistry, pharmacology)
• Flow Cytometry
• Humans
• Inhibitory Concentration 50
• Lactones (chemistry, pharmacology)
• Light
• Mouth Neoplasms (drug therapy, metabolism, pathology)
• Nasopharyngeal Neoplasms (drug therapy, metabolism, pathology)
• Photochemotherapy (methods)
• Photosensitizing Agents (chemistry, pharmacology)
• Plant Extracts (chemistry, pharmacology)
• Singlet Oxygen (metabolism)
• Spectrum Analysis