Abstract

Abstract Neuroblastoma is an extra-cranial tumour of childhood and arises from the sympatho-adrenal lineage of the neural crest tissue. Despite advances in treatment strategies, significant complications in curing this cancer remain. Furthermore, severe consequential effects on patient health have been associated with chemotherapy and/or radiation. Photodynamic therapy (PDT) with the photosensitiser hypericin (HYP) presents an attractive and efficient adjunctive therapy alternative for this aggressive cancer. HYP, an extract from Hypericum perforatum (St John's Wort) species, has a high quantum yield following photo-activation and a low dark toxicity and genotoxiciy. This study tests the anti-cancer efficacy of HYP-PDT in SK-N-SH neuroblastoma cells using an in vitro tissue culture model. Results show through detailed uptake kinetics that HYP is absorbed effectively by SK-N-SH cells after 6 hours of incubation and live fluorescent confocal microscopy revealed primary localisation of HYP to lysosomes and mitochondria. Through cell viability assays it was determined that 2, 3 and 4μM HYP-PDT resulted in 45.6±5.1% cell death within 24 hours of treatment. Additionally, 24 hours post 0.25μM and 2μM HYP-PDT, we observed distinct morphological changes in SK-N-SH cells using phase contrast microscopy, and determined a high apoptotic mode of cell death using Fluorescent Activated Cell Sorting (FACS). These results demonstrate that HYP-PDT is effective in killing neuroblastoma cells and that the mode of cell death is apoptotic in nature. This study is ongoing with further investigation into the signalling underlying this photo-toxicity with particular emphasis on cell death resistance mechanisms in neuroblastoma cells. Citation Format: Lester M. Davids, Anja Schwar, Dirk Lang. A theranostic approach using photodynamic therapy to efficiently kill neuroblastoma cancer cells through induction of apoptosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3201.

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