Abstract 3464: Aminolevulinic acid-mediated photodynamic therapy induces cell death in human osteosarcoma cells

Abstract

Abstract Photodynamic therapy (PDT) is a localized cancer treatment that requires a photosensitizer (PS), molecular oxygen, and light to induce cell death. Aminolevulinic acid (ALA)-mediated PDT utilizes ALA as an inert precursor to the required PS. Subsequent to cellular uptake ALA is converted to a PS, protoporphyrin IX (PpIX), in the mitochondria via the heme pathway. The excitation of PpIX by light can then result in the generation of reactive oxygen species, leading to direct tumor cell death, damage to the microvasculature, and induction of local inflammatory response. Interestingly, PDT can evoke apoptotic and/or necrotic cell death pathways within the same cell population. The balance between apoptosis and necrosis depends on several parameters, including the total PDT dose, the intracellular localization of the PS, the fluence rate, and the cell type. Recent studies show that the cell death mechanism induced has a direct influence on the systemic immune response. Therefore, a better understanding of the interplay between different cell death mechanisms in response to PDT could lead to improved tumor response and could inform better therapeutic strategies. We first determined the cytotoxicity of ALA to the human osteosarcoma cell line MG-63. PDT is a relatively unexplored method of treatment for human osteosarcoma, and could represent a superior method to existing therapies. Data from our lab show that ALA is not significantly cytotoxic to MG-63 cells, and that it is efficiently converted to PpIX within 24 hours of treatment. We also demonstrate that ALA-mediated PDT significantly induces cell death in MG-63 cells, and that cell death increases with increased ALA concentration and light fluence. Our findings indicate that this cell death results from a combination of both apoptosis and necrosis, with necrosis representing the major pathway. Finally, we show that increased light fluence decreases the amount of observed apoptosis subsequent to ALA-mediated PDT. These results taken together suggest that ALA-mediated PDT can induce cell death in human osteosarcoma cells, and that most cells are dying by necrosis. Furthermore, our data suggests that by adjusting specific therapeutic parameters, we can shift the balance between separate death pathways. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3464. doi:1538-7445.AM2012-3464