A potent nonporphyrin class of photodynamic therapeutic agent: Cellular localisation, cytotoxic potential and influence of hypoxia

Gallagher, W. M., Allen, L. T., O'Shea, C., Kenna, T., Hall, M., Gorman, A., Killoran, J., & O'Shea, D. F. (2005) A potent nonporphyrin class of photodynamic therapeutic agent: Cellular localisation, cytotoxic potential and influence of hypoxia. British Journal of Cancer, 92(9), pp. 1702-1710.

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Abstract

We have developed a totally new class of nonporphyrin photodynamic therapeutic agents with a specific focus on two lead candidates azadipyrromethene (ADPM)01 and ADPM06. Confocal laser scanning microscopy imaging showed that these compounds are exclusively localised to the cytosolic compartment, with specific accumulation in the endoplasmic reticulum and to a lesser extent in the mitochondria. Light-induced toxicity assays, carried out over a broad range of human tumour cell lines, displayed EC50 values in the micro-molar range for ADPM01 and nano-molar range for ADPM06, with no discernable activity bias for a specific cell type. Strikingly, the more active agent, ADPM06, even retained significant activity under hypoxic conditions. Both photosensitisers showed low to nondeterminable dark toxicity. Flow cytometric analysis revealed that ADPM01 and ADPM06 were highly effective at inducing apoptosis as a mode of cell death. The photophysical and biological characteristics of these PDT agents suggest that they have potential for the development of new anticancer therapeutics. © 2005 Cancer Research UK.

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ID Code: 94056
Item Type: Journal Article
Refereed: Yes
Additional URLs:
Keywords: Cellular localisation, Cytotoxic potential, Photodynamic therapeutic agent, adpm 01, adpm 06, azadipyrromethene, photosensitizing agent, unclassified drug, apoptosis, article, cancer cell culture, cell survival, cell viability, cellular distribution, confocal laser microscopy, cytotoxicity, dose response, flow cytometry, HeLa cell, human, human cell, hypoxia, immunofluorescence microscopy, photodynamic therapy, photosensitization, priority journal, Cell Hypoxia, Cell Line, Tumor, Cytoplasm, Dose-Response Relationship, Drug, Endoplasmic Reticulum, Humans, Light, Photochemotherapy, Photosensitizing Agents, Porphyrins, Pyrroles
DOI: 10.1038/sj.bjc.6602527
ISSN: 1532-1827
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2005 Cancer Research UK
Copyright Statement: From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License.
Deposited On: 21 Mar 2016 02:10
Last Modified: 21 Mar 2016 02:12

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