The effect of ALA/PpIX PDT on putative cancer stem cells in tumor side populations

Janet Morgan; Cara M. Petrucci

doi:10.1117/12.822622

13 July 2009 The effect of ALA/PpIX PDT on putative cancer stem cells in tumor side populations

Janet Morgan, Cara M. Petrucci

Proceedings Volume 7380, Photodynamic Therapy: Back to the Future; 738011 (2009) https://doi.org/10.1117/12.822622
Event: 12th World Congress of the International Photodynamic Association, 2009, Seattle, Washington, United States

Abstract

Protoporphyrin IX (PpIX) synthesized endogenously from 5-aminolevulinic acid (ALA), is effluxed from cells expressing the ATP-dependent transporter ABCG2. Side population (SP) cells (named for their low red/blue fluorescence distribution in flow cytometry plots with ABCG2 substrates such as Hoechst) are postulated to contain cancer stem cells (CSC). The SP in U87 (human gliblastoma cell line) were more resistant to ALA-PDT than NON-SP cells. Inhibiting ABCG2 activity with the tyrosine kinase inhibitor imatinib mesylate (IM, Gleevec) during incubation with ALA increased PpIX in the SP by preventing its efflux and decreased the SP after subsequent PDT, enhancing phototoxicity. Evasion of SP cells from ALA-PDT could cause tumor recurrence from CSC. Manipulation of ABCG2 levels on the SP with small molecule modulators may be a potential strategy for enhancing PDT by decreasing the amount of substrate photosensitizer extruded from cells and lowering the threshold for phototoxicity.

Citation Download Citation

Janet Morgan and Cara M. Petrucci "The effect of ALA/PpIX PDT on putative cancer stem cells in tumor side populations", Proc. SPIE 7380, Photodynamic Therapy: Back to the Future, 738011 (13 July 2009); https://doi.org/10.1117/12.822622

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