Targeting tumour energy metabolism potentiates the cytotoxicity of 5-aminolevulinic acid photodynamic therapy

Background: Cancerous cells usually exhibit increased aerobic glycolysis, compared with normal tissue (the Warburg effect), making this pathway an attractive therapeutic target. Methods: Cell viability, cell number, clonogenic assay, reactive oxygen (ROS), ATP, and apoptosis were assayed in MCF-7 tu...

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Bibliographic Details
Published in:	British journal of cancer Vol. 109; no. 4; pp. 976 - 982
Main Authors:	Golding, J P, Wardhaugh, T, Patrick, L, Turner, M, Phillips, J B, Bruce, J I, Kimani, S G
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 20-08-2013 Nature Publishing Group
Subjects:	631/67/1059 631/67/2327 Acids Adenosine Triphosphate - metabolism Aminolevulinic Acid - administration & dosage Antimetabolites - administration & dosage Antineoplastic Agents - administration & dosage Antineoplastic Combined Chemotherapy Protocols - pharmacology Apoptosis Biological and medical sciences Biomedical and Life Sciences Biomedicine Cancer Research Cancer therapies Cell cycle Cell Line, Tumor - drug effects Cytotoxicity Deoxyglucose - administration & dosage Drug Administration Schedule Drug Resistance Epidemiology Glycolysis - drug effects Hexokinase - antagonists & inhibitors Humans Indazoles - administration & dosage Mammary Glands, Human - cytology MCF-7 Cells Medical sciences Metabolism Metabolites Molecular Medicine Oncology Photochemotherapy Photodynamic therapy Photosensitizing Agents - administration & dosage Reactive Oxygen Species - metabolism Translational Therapeutics Tumor Stem Cell Assay Tumors United Kingdom > UK photodynamic therapy metabolism glycolysis 5-Aminolevulinic acid Energy metabolism Cancerology Photodynamic therapy Treatment Targeting Glycolysis Cytotoxicity Tumor
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Summary:	Background: Cancerous cells usually exhibit increased aerobic glycolysis, compared with normal tissue (the Warburg effect), making this pathway an attractive therapeutic target. Methods: Cell viability, cell number, clonogenic assay, reactive oxygen (ROS), ATP, and apoptosis were assayed in MCF-7 tumour cells and corresponding primary human mammary epithelial cells (HMEC). Results: Combining the glycolysis inhibitors 2-deoxyglucose (2DG; 180 m M ) or lonidamine (300 μ M ) with 10 J cm −2 5-aminolevulinic acid (ALA) photodynamic therapy (PDT) increases MCF-7 cytotoxicity (by 3.5-fold to 70% death after 24 h, and by 10-fold in 9-day clonogenic assays). However, glycolysis inhibition only slightly increases HMEC PDT cytotoxicity (between two-fold and three-fold to a maximum of 9% death after 24 h). The potentiation of PDT cytotoxicity only occurred if the glycolysis inhibitors were added after ALA incubation, as they inhibited intracellular accumulation of photosensitiser if coincubated with ALA. Conclusion: As 2DG and lonidamine are already used as cancer chemotherapeutic agents, our results are directly translatable to combination therapies with existing topical PDT.
ISSN:	0007-0920 1532-1827
DOI:	10.1038/bjc.2013.391