Cancer cell spheroids are a better screen for the photodynamic efficiency of glycosylated photosensitizers

Photodynamic Therapy (PDT) relies on the use of non-toxic photosensitizers that are locally and selectively activated by light to induce cell death or apoptosis through reactive oxygen species generation. The conjugation of porphyrinoids with sugars that target cancer is increasingly viewed as an ef...

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Bibliographic Details
Published in:	PloS one 2017-05, Vol.12 (5), p.e0177737-e0177737
Main Authors:	Pereira, Patrícia M R, Berisha, Naxhije, Bhupathiraju, N V S Dinesh K, Fernandes, Rosa, Tomé, João P C, Drain, Charles Michael
Format:	Article
Language:	eng
Subjects:	Analysis Apoptosis Biology and Life Sciences Bladder cancer Breast cancer Cancer Cancer therapies Cell culture Cell Culture Techniques - methods Cell death Cell Line, Tumor Cell Proliferation - drug effects Cell Survival - drug effects Cervical cancer Chemotherapy Colorectal cancer Galectin 1 - metabolism Galectin-1 Gangrene Gene expression Gene Expression Regulation, Neoplastic - drug effects Glucose Glucose - metabolism Glucose transporter Glucose Transporter Type 1 - metabolism GLUT1 protein Glycosylation HCT116 Cells Health aspects HeLa Cells Humans Hypoxia MCF-7 Cells Medicine and Health Sciences Metabolism Metabolites Nutrients Oxygen Photochemotherapy Photodynamic therapy Photosensitizing Agents - chemistry Photosensitizing Agents - pharmacology Phototoxicity Physical Sciences Porphyrins - chemistry Porphyrins - pharmacology Protein transport Reactive oxygen species Reactive Oxygen Species - metabolism Research and Analysis Methods Risk factors Selectivity Spatial distribution Spheroids Spheroids, Cellular - cytology Spheroids, Cellular - drug effects Sugar Sugars Tumor cell lines Tumor Cells, Cultured - cytology Tumor Cells, Cultured - drug effects Tumors
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Summary:	Photodynamic Therapy (PDT) relies on the use of non-toxic photosensitizers that are locally and selectively activated by light to induce cell death or apoptosis through reactive oxygen species generation. The conjugation of porphyrinoids with sugars that target cancer is increasingly viewed as an effective way to increase the selectivity of PDT. To date, in vitro PDT efficacy is mostly screened using two-dimensional monolayer cultures. Compared to monolayer cultures, three-dimensional spheroid cultures have unique spatial distributions of nutrients, metabolites, oxygen and signalling molecules; therefore better mimic in vivo conditions. We obtained 0.05 mm3 spheroids with four different human tumor cell lines (HCT-116, MCF-7, UM-UC-3 and HeLa) with appropriate sizes for screening PDT agents. We observed that detachment from monolayer culture and growth as tumor spheroids was accompanied by changes in glucose metabolism, endogenous ROS levels, galectin-1 and glucose transporter GLUT1 protein levels. We compared the phototoxic responses of a porphyrin conjugated with four glucose molecules (PorGlu4) in monolayer and spheroid cultures. The uptake and phototoxicity of PorGlu4 is highly dependent on the monolayer versus spheroid model used and on the different levels of GLUT1 protein expressed by these in vitro platforms. This study demonstrates that HCT-116, MCF-7, UM-UC-3 and HeLa spheroids afford a more rational platform for the screening of new glycosylated-photosensitizers compared to monolayer cultures of these cancer cells.
ISSN:	1932-6203 1932-6203